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Long noncoding RNAs (lncRNAs) play important roles in the progression of human cancer. It is reported that lncRNA plasmacytoma variant translocation 1 (PVT1) is involved in colorectal cancer (CRC), however, the underlying mechanism remains to be explored deeply, especially by in vivo models. In the present study, bioinformatics analysis showed that the expression level of PVT1 was upregulated in CRC tissues and highly associated with poor prognosis of CRC patients. In cultured CRC cells, knockdown of PVT1 inhibited cell proliferation and migration of CRC cells, while overexpression of PVT1 promoted the progression of CRC cells. In zebrafish xenograffs, the silencing of PVT1 also suppressed the growth and metastasis of CRC cells. For mechanism studies, the binding relationships among PVT1, miR-24-3p, and Neuropilin 1 (NRP1) were predicted by starBase firstly. filuciferase reporter assays verified that PVT1 and NRP1 could bind with miR-24-3p directly. Further studies showed miR-24-3p negatively regulated the progression of CRC cells, the inhibition of miR-24-3p counteracted the repression effects of CRC progression when knocking down PVT1. In addition, the expression of NRP1 was regulated by PVT1, and NRP1 overexpression could partially rescue the inhibition effects of CRC progression when knocking down PVT1 in vitro and in vivo. Our study reveals that PVT1 promotes the proliferation and metastasis of CRC via regulating the miR-24-3p/NRP1 axis, which provides a prognosis biomarker and a potential therapeutic target for CRC patients. [ABSTRACT FROM AUTHOR]

Phytoplasmas are uncultivable, phloem-limited, phytopathogenic bacteria that represent a major threat to agriculture worldwide. Phytoplasma membrane proteins are in direct contact with hosts and presumably play a crucial role in phytoplasma spread within the plant as well as by the insect vector. Three highly abundant types of immunodominant membrane proteins (IDP) have been identified within the phytoplasmas: immunodominant membrane protein (Imp), immunodominant membrane protein A (IdpA), and antigenic membrane protein (Amp). Although recent results indicate that Amp is involved in host specificity by interacting with host proteins such as actin, little is known about the pathogenicity of IDP in plants. In this study, we identified an antigenic membrane protein (Amp) of rice orange leaf phytoplasma (ROLP), which interacts with the actin of its vector. In addition, we generated Amp-transgenic lines of rice and expressed Amp in tobacco leaves by the potato virus X (PVX) expression system. Our results showed that the Amp of ROLP can induce the accumulation of ROLP and PVX in rice and tobacco plants, respectively. Although several studies have reported interactions between major phytoplasma antigenic membrane protein (Amp) and insect vector proteins, this example demonstrates that Amp protein can not only interact with the actin protein of its insect vector but can also directly inhibit host defense responses to promote the infection. The function of ROLP Amp provides new insights into the phytoplasma-host interaction. [ABSTRACT FROM AUTHOR]

Background. The role of N6-methyladenosine long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) is elusive. Materials and Methods. We identified m6A-associated lncRNAs by using the data gathered from The Cancer Genome Atlas (TCGA) and stratified CRC patients into different subgroups. Cox regression analysis was performed to construct an m6A-associated lncRNA signature. The role of this signature in the immune microenvironment and prognosis was dissected subsequently. Finally, a gene set enrichment analysis (GSEA) was conducted to predict the possible mechanisms based on the signature. Results. Three m6A-associated clusters were constructed from 866 differentially expressed lncRNAs. Cluster 2 had poor prognosis and low immune cell infiltration. An m6A-associated lncRNA signature consisting of 14 lncRNAs was constructed and recognized as an independent prognostic indicator of CRC by using survival analysis and receiver operating characteristic (ROC) curves. The clinical features and immune cell infiltration status were significantly different in patients stratified by the risk score. Furthermore, GSEA showed that the P53 pathway and natural killer cell-mediated cytotoxicity were more enriched in the low-risk group. Conclusion. Our data revealed that m6A-associated lncRNAs could be potential prognostic indicators of immunogenicity in CRC. [ABSTRACT FROM AUTHOR]

Quantization is a promising technique to reduce the computation and storage costs of DNNs. Low-bit ($\leq8$ bits) precision training remains an open problem due to the difficulty of gradient quantization. In this paper, we find two long-standing misunderstandings of the bias of gradient quantization noise. First, the large bias of gradient quantization noise, instead of the variance, is the key factor of training accuracy loss. Second, the widely used stochastic rounding cannot solve the training crash problem caused by the gradient quantization bias in practice. Moreover, we find that the asymmetric distribution of gradients causes a large bias of gradient quantization noise. Based on our findings, we propose a novel adaptive piecewise quantization method to effectively limit the bias of gradient quantization noise. Accordingly, we propose a new data format, Piecewise Fixed Point (PWF), to present data after quantization. We apply our method to different applications including image classification, machine translation, optical character recognition, and text classification. We achieve approximately $1.9\sim 3.5\times $ speedup compared with full precision training with an accuracy loss of less than 0.5%. To the best of our knowledge, this is the first work to quantize gradients of all layers to 8 bits in both large-scale CNN and RNN training with negligible accuracy loss. [ABSTRACT FROM AUTHOR]

Inspired by simultaneous localization and mapping (SLAM) style workflow, this article presented an online sequential structure from motion (SfM) solution for high-frequency video and large baseline high-resolution aerial images with high efficiency and novel precision. First, as traditional SLAM systems are not good in processing low overlap images, based on our novel hierarchical feature matching paradigm with multihomography and BoW, we proposed a robust tracking method where the relative pose and its scale are estimated separately followed by a joint optimization by considering both perspective-n-point (PnP) and epipolar constraints. Second, to further optimize the camera poses for the sparse map and dense pointcloud reconstruction, we provided a graph-based optimization with reprojection and GPS constraints, which make the camera trajectory and map georeferenced. We also incrementally generated the dense point cloud in real time from keyframes after local mapping optimization. Finally, we use a publicly available aerial image dataset with sequences of different environments, to evaluate the effectiveness of the proposed method, meanwhile, the robust performance of our solution is demonstrated with applications of high-quality aerial images mosaic and digital surface model (DSM) reconstruction in real time. Compared with the state-of-the-art SLAM and traditional SfM methods, the presented system can output large-scale high-quality ortho-mosaic and DSM in real time with the low computational cost. [ABSTRACT FROM AUTHOR]

Ligand-gated ion channels display a fundamental property - channels remain virtually closed at rest and open upon agonist binding. Here we show that substituting alanines for either of two amino acid residues (T314 or L317) in the M2 region of the [Gamma]-aminobutyric acid (GABA) [Rho]1 subunit results in spontaneous channel opening in the absence of ligand. Surprisingly, for two single point mutants (T314A or L317A), application of very low concentrations of agonist partially suppressed this spontaneous current, while higher concentrations re-activated the receptors. When both of these sites were mutated (T314A/L317A), GABA nearly completely suppressed the constitutive current and did not re-activate the current even at very high concentrations. This study provides important new insights into the structure-function relationship of ligand-gated ion channels, where modification of the structure of the channel pore region not only alters the allosteric transition of the receptor protein but also reverses the polarity of agonist regulation of channel gating. Our results suggest that the sites where these two residues are located are structurally critical for channel gating.

Ionotropic receptors for [gamma]-aminobutyric acid (GABA) are important to inhibitory neurotransmission in the mammalian retina, mediating [GABA.sub.A] and [GABA.sub.C] responses. In many species, these responses are blocked by the convulsant picrotoxinin (PTX), although the mechanism of block is not fully understood. In contrast, [GABA.sub.C] responses in the rat retina are extremely resistant to PTX. We hypothesized that this difference could be explained by molecular characterization of the receptors underlying the [GABA.sub.C] response. Here we report the cloning of two rat GABA receptor subunits, designated r[rho]1 and r[rho]2 after their previously identified human homologues. When coexpressed in Xenopus oocytes, r[rho]1/r[rho]2 heteromeric receptors mimicked PTX-resistant [GABA.sub.C] responses of the rat retina. PTX resistance is apparently conferred in native heteromeric receptors by r[rho]2 subunits since homomeric r[rho]1 receptors were sensitive to PTX; r[rho]2 subunits alone were unable to form functional homomeric receptors. Site-directed mutagenesis confirmed that a single amino acid residue in the second membrane-spanning region (a methionine in r[rho]2 in place of a threonine in r[rho]1) is the predominant determinant of PTX resistance in the rat receptor. This study reveals not only the molecular mechanism underlying PTX blockade of GABA receptors but also the heteromeric nature of native receptors in the rat retina that underlie the PTX-resistant [GABA.sub.C] response.

When packing for a journey, have you ever asked “what clothes should I take with me?” Wearing appropriate and aesthetically pleasing clothing when traveling is a concern for many of us. Our data observation of photos from several popular travel websites reveals that people's choice of clothing items and their color combinations have strong correlations with the weather, the season, and the main type of attraction at the destination. This leads to an interesting and novel problem: can the correlation between clothing and locations be automatically learned from social photos and leveraged for location-oriented clothing recommendations? In this paper, we systematically study this problem and propose a hybrid multilabel convolutional neural network combined with the support vector machine (mCNN-SVM) approach to capture the intrinsic and complex correlations between clothing attributes and location attributes. Specifically, we adapt the CNN architecture to multilabel learning and fine-tune it using each fine-grained clothing item. Then, the recognized items are fed to the SVM to learn the correlations. Experiments on three fashion datasets and a benchmark journey outfit dataset show that our proposed approach outperforms several baselines by over 10.52–16.38% in terms of the mAP for clothing item recognition and outperforms several alternative methods by over 9.59–29.41% in terms of the mAP when ranking clothing by appropriateness for travel destinations. Finally, an interesting case study demonstrates the effectiveness of our method by answering what items to wear, how to match them, and how to dress in an aesthetically pleasing manner for a journey. [ABSTRACT FROM PUBLISHER]

We present a deep learning strategy to fuse multiple semantic cues for complex event recognition. In particular, we tackle the recognition task by answering how to jointly analyze human actions (who is doing what), objects (what), and scenes (where). First, each type of semantic features (e.g., human action trajectories) is fed into a corresponding multi-layer feature abstraction pathway, followed by a fusion layer connecting all the different pathways. Second, the correlations of how the semantic cues interacting with each other are learned in an unsupervised cross-modality autoencoder fashion. Finally, by fine-tuning a large-margin objective deployed on this deep architecture, we are able to answer the question on how the semantic cues of who, what, and where compose a complex event. As compared with the traditional feature fusion methods (e.g., various early or late strategies), our method jointly learns the essential higher level features that are most effective for fusion and recognition. We perform extensive experiments on two real-world complex event video benchmarks, MED’11 and CCV, and demonstrate that our method outperforms the best published results by 21% and 11%, respectively, on an event recognition task. [ABSTRACT FROM AUTHOR]

The task of recognizing events from video has attracted a lot of attention in recent years. However, due to the complex nature of user-defined events, the use of purely audio- visual content analysis without domain knowledge has been found to be grossly inadequate. In this paper, we propose to construct a semantic-visual knowledge base to encode the rich event-centric concepts and their relationships from the well- established lexical databases, including FrameNet, as well as the concept-specific visual knowledge from ImageNet. Based on this semantic-visual knowledge bases, we design an effective system for video event recognition. Specifically, in order to narrow the semantic gap between the high-level complex events and low-level visual representations, we utilize the event-centric semantic concepts encoded in the knowledge base as the intermediate-level event representation, which offers both human-perceivable and machine-interpretable semantic clues for event recognition. In addition, in order to leverage the abundant ImageNet images, we propose a robust transfer learning model to learn the noise- resistant concept classifiers for videos. Extensive experiments on various real-world video datasets demonstrate the superiority of our proposed system as compared to the state-of-the-art approaches. [ABSTRACT FROM PUBLISHER]

Background/Aims: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterised by prominent synoviocyte hyperplasia and a potential imbalance between the growth and death of fibroblast-like synoviocytes (FLS). Mitomycin C (MMC) has previously been demonstrated to inhibit fibroblast proliferation and to induce fibroblast apoptosis. However, the effects of MMC on the proliferation and apoptosis of human RA FLS and the potential mechanisms underlying its effects remain unknown. Methods: Cell viability was determined using the Cell Counting Kit-8 assay. Apoptotic cell death was analysed via Annexin V-FITC/PI double staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling. The production of intracellular reactive oxygen species (ROS) was assessed via flow cytometry, and the changes in mitochondrial membrane potential (ΔΨm) were visualized based on JC-1 staining via fluorescence microscopy. The expression of apoptosis-related proteins was determined via Western blot. Results: Treatment with MMC significantly reduced cell viability and induced apoptosis in RA FLS. Furthermore, MMC exposure was found to stimulate the production of ROS and to disrupt the ΔΨm compared to the control treatment. Moreover, MMC increased the release of mitochondrial cytochrome c, the ratio of Bax/Bcl-2, the activation of caspase-9 and caspase-3, and the subsequent cleavage of poly(ADP-ribose) polymerase. Conclusion: Our findings suggest that MMC inhibits cell proliferation and induces apoptosis in RA FLS, and the mechanism underlying this MMC-induced apoptosis may involve a mitochondrial signalling pathway. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

From cultural system view point, the modernization of society accompanying the cultural awareness is a process of cultural modernization. In essence, this is a process of utilizing the ultimate achievements of Western civilization hence absorbing, borrowing and innovatively transforming Chinese national culture to produce the nationalization and crystallization of Marxism. Marxist Sinicilization is a process of reconstruction, consolidation, and innovation between the host cultural entity and guest entity. The cultural significance of Marxist Sinicilization is twofold, it not only produce the nationalization and crystallization of Marxism, but also represents the direction of Chinese cultural modernization. The rapid spread of Marxism in China and its Sinicilization is the unavoidable choice of Chinese contemporary history, and this is a logical development of the Chinese ideology and culture. Nevertheless, the negative aspects of Chinese cultural tradition resulted historical impediments and downturns which rendered ideological and cultural lessons. [ABSTRACT FROM AUTHOR]

AbstractFunctional coassembly of γ-aminobutyric acid (GABA)C ρ1 subunits with GABAA (α1, β2, and γ2S) or glycine (α1, α2, and β) subunits was examined using two-electrode voltage-clamp recordings in the Xenopus laevis oocyte expression system. To facilitate this study, we took advantage of the unique gating and pharmacological properties of two mutant ρ1 subunits, ρ1(T314A) and ρ1(T314A/L317A). When the ρ1(T314A) subunit was coexpressed with GABA γ2S, glycine α1 or glycine α2 subunits, GABA response properties were different from those of homomeric ρ1(T314A) receptors. Additionally, the sensitivity of heteromeric ρ1(T314A) and γ2S receptors to picrotoxinin (PTX) blockade of GABA-evoked responses was altered compared to that of homomeric ρ1(T314A) receptors. Changes in GABA response properties and picrotoxinin sensitivity were also observed when ρ1(T314A) subunits were coexpressed with wild-type ρ1 subunits. When ρ1(T314A/L317A) subunits were coexpressed with GABA γ2S, glycine α1 or glycine α2 subunits, suppression by GABA of spontaneously active current was reduced compared to that of homomeric ρ1(T314A/L317A) receptors. Recovery of the spontaneous current from inhibition by GABA for GABA ρ1(T314A/L317A)/γ2S heteromeric receptors displayed an additional component. Coinjection of wild-type ρ1 with γ2S cRNAs at a ratio of 1 : 1 resulted in a > 10-fold reduction in GABA-evoked current. Furthermore, coexpression of wild-type ρ1 and γ2S subunits was found to shift the GABA dose–response curve. Our results provide functional evidence that the GABAC ρ1 subunit can coassemble with the GABAA γ2S subunit, and, at least in its mutated form, ρ1 can also form heteromeric receptors with glycine α1 or α2... [ABSTRACT FROM AUTHOR]

Orthophoto generation is a popular topic in aerial photogrammetry and 3D reconstruction. It is generally computationally expensive with large memory consumption. Inspired by the simultaneous localization and mapping (SLAM) workflow, this paper presents an online sequential orthophoto mosaicing solution for large baseline high-resolution aerial images with high efficiency and novel precision. An appearance and spatial correlation-constrained fast low-overlap neighbor candidate query and matching strategy is used for efficient and robust global matching. Instead of estimating 3D positions of sparse mappoints, which is outlier sensitive, we propose to describe the ground reconstruction with multiple stitching planes, where parameters are reduced for fast nonconvex graph optimization. GPS information is also fused along with six degrees of freedom (6-DOF) pose estimation, which not only provides georeferenced coordinates, but also converges property and robustness. An incremental orthophoto is generated by fusing the latest images with adaptive weighted multiband algorithm, and all results are tiled with level of detail (LoD) support for efficient rendering and further disk cache for reducing memory usages. Public datasets are evaluated by comparing state-of-the-art software. Results show that our system outputs orthophoto with novel efficiency, quality, and robustness in real-time. An android commercial application is developed for online stitching with DJIdrones, considering the excellent performance of our algorithm. [ABSTRACT FROM AUTHOR]

The etiology of lumbocrural pain is tightly concerned with intervertebral disk degeneration (IDD). Bone mesenchymal stem cell (BMSC)-based therapy bears potentials for IDD treatment. The properties of microRNA (miRNA)-modified BMSCs may be altered. This study investigated the role and mechanism of BMSCs promoting extracellular matrix (ECM) remodeling of degenerated nucleus pulposus cells (NPCs) via the miR-101-3p/EIF4G2 axis. NPCs were collected from patients with IDD and lumbar vertebral fracture (LVF). The expressions of miR-101-3p and ECM-related proteins, Collagen-I (Col-I) and Collagen-II (Col-II), were detected using the reverse transcription-quantitative polymerase chain reaction. The expressions of Col-I and Col-II, major non-collagenous component Aggrecan, and major catabolic factor Matrix metalloproteinase-13 (MMP-13) were detected using Western blotting. BMSCs were cocultured with degenerated NPCs from patients with IDD. Viability and apoptosis of NPCs were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. After the degenerated NPCs were transfected with the miR-101-3p inhibitor, the expressions of ECM-related proteins, cell viability, and apoptosis were detected. The targeting relationship between miR-101-3p and EIF4G2 was verified. Functional rescue experiments verified the effects of miR-101-3p and EIF4G2 on ECM remodeling of NPCs. Compared with the NPCs of patients with LVF, the degenerated NPCs of patients with IDD showed downregulated miR-101-3p, Col-II, and Aggrecan expressions and upregulated MMP-13 and Col-I expressions. BMSCs increased the expressions of miR-101-3p, Aggrecan, and Col-II, and decreased the expressions of MMP-13 and Col-I in degenerated NPCs. BMSCs enhanced NPC viability and repressed apoptosis. Downregulation of miR-101-3p suppressed the promoting effect of BMSCs on ECM remodeling. miR-101-3p targeted EIF4G2. Downregulation of EIF4G2 reversed the inhibiting effect of the miR-101-3p inhibitor on ECM remodeling. In conclusion, BMSCs increased the miR-101-3p expression in degenerated NPCs to target EIF4G2, thus promoting the ECM remodeling of NPCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Ding, Cao, Zhang and Wu.)