Journal articles on the topic 'GELUs activation function'
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1
Li, Chengfan, Yueyu Qi, Xuehai Ding, Junjuan Zhao, Tian Sang, and Matthew Lee. "A Deep Learning Method Approach for Sleep Stage Classification with EEG Spectrogram." International Journal of Environmental Research and Public Health 19, no. 10 (May 23, 2022): 6322. http://dx.doi.org/10.3390/ijerph19106322.
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The classification of sleep stages is an important process. However, this process is time-consuming, subjective, and error-prone. Many automated classification methods use electroencephalogram (EEG) signals for classification. These methods do not classify well enough and perform poorly in the N1 due to unbalanced data. In this paper, we propose a sleep stage classification method using EEG spectrogram. We have designed a deep learning model called EEGSNet based on multi-layer convolutional neural networks (CNNs) to extract time and frequency features from the EEG spectrogram, and two-layer bi-directional long short-term memory networks (Bi-LSTMs) to learn the transition rules between features from adjacent epochs and to perform the classification of sleep stages. In addition, to improve the generalization ability of the model, we have used Gaussian error linear units (GELUs) as the activation function of CNN. The proposed method was evaluated by four public databases, the Sleep-EDFX-8, Sleep-EDFX-20, Sleep-EDFX-78, and SHHS. The accuracy of the method is 94.17%, 86.82%, 83.02% and 85.12%, respectively, for the four datasets, the MF1 is 87.78%, 81.57%, 77.26% and 78.54%, respectively, and the Kappa is 0.91, 0.82, 0.77 and 0.79, respectively. In addition, our proposed method achieved better classification results on N1, with an F1-score of 70.16%, 52.41%, 50.03% and 47.26% for the four datasets.
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Wang, Xuyang, and Yixuan Tong. "Application of an emotional classification model in e-commerce text based on an improved transformer model." PLOS ONE 16, no. 3 (March 5, 2021): e0247984. http://dx.doi.org/10.1371/journal.pone.0247984.
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With the rapid development of the mobile internet, people are becoming more dependent on the internet to express their comments on products or stores; meanwhile, text sentiment classification of these comments has become a research hotspot. In existing methods, it is fairly popular to apply a deep learning method to the text classification task. Aiming at solving information loss, weak context and other problems, this paper makes an improvement based on the transformer model to reduce the difficulty of model training and training time cost and achieve higher overall model recall and accuracy in text sentiment classification. The transformer model replaces the traditional convolutional neural network (CNN) and the recurrent neural network (RNN) and is fully based on the attention mechanism; therefore, the transformer model effectively improves the training speed and reduces training difficulty. This paper selects e-commerce reviews as research objects and applies deep learning theory. First, the text is preprocessed by word vectorization. Then the IN standardized method and the GELUs activation function are applied based on the original model to analyze the emotional tendencies of online users towards stores or products. The experimental results show that our method improves by 9.71%, 6.05%, 5.58% and 5.12% in terms of recall and approaches the peak level of the F1 value in the test model by comparing BiLSTM, Naive Bayesian Model, the serial BiLSTM_CNN model and BiLSTM with an attention mechanism model. Therefore, this finding proves that our method can be used to improve the text sentiment classification accuracy and effectively apply the method to text classification.
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Paul, Ashis, Rajarshi Bandyopadhyay, Jin Hee Yoon, Zong Woo Geem, and Ram Sarkar. "SinLU: Sinu-Sigmoidal Linear Unit." Mathematics 10, no. 3 (January 23, 2022): 337. http://dx.doi.org/10.3390/math10030337.
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Non-linear activation functions are integral parts of deep neural architectures. Given the large and complex dataset of a neural network, its computational complexity and approximation capability can differ significantly based on what activation function is used. Parameterizing an activation function with the introduction of learnable parameters generally improves the performance. Herein, a novel activation function called Sinu-sigmoidal Linear Unit (or SinLU) is proposed. SinLU is formulated as SinLU(x)=(x+asinbx)·σ(x), where σ(x) is the sigmoid function. The proposed function incorporates the sine wave, allowing new functionalities over traditional linear unit activations. Two trainable parameters of this function control the participation of the sinusoidal nature in the function, and help to achieve an easily trainable, and fast converging function. The performance of the proposed SinLU is compared against widely used activation functions, such as ReLU, GELU and SiLU. We showed the robustness of the proposed activation function by conducting experiments in a wide array of domains, using multiple types of neural network-based models on some standard datasets. The use of sine wave with trainable parameters results in a better performance of SinLU than commonly used activation functions.
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Zamora, Julio, Anthony D. Rhodes, and Lama Nachman. "Fractional Adaptive Linear Units." Proceedings of the AAAI Conference on Artificial Intelligence 36, no. 8 (June 28, 2022): 8988–96. http://dx.doi.org/10.1609/aaai.v36i8.20882.
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This work introduces Fractional Adaptive Linear Units (FALUs), a flexible generalization of adaptive activation functions. Leveraging principles from fractional calculus, FALUs define a diverse family of activation functions (AFs) that encompass many traditional and state-of-the-art activation functions. This family includes the Sigmoid, Gaussian, ReLU, GELU, and Swish functions, as well as a large variety of smooth interpolations between these functions. Our technique requires only a small number of additional trainable parameters, and needs no further specialized optimization or initialization procedures. For this reason, FALUs present a seamless and rich automated solution to the problem of activation function optimization. Through experiments on a variety of conventional tasks and network architectures, we demonstrate the effectiveness of FALUs when compared to traditional and state-of-the-art AFs. To facilitate practical use of this work, we plan to make our code publicly available
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Herrera, Oscar, and Belém Priego. "Wavelets as activation functions in Neural Networks." Journal of Intelligent & Fuzzy Systems 42, no. 5 (March 31, 2022): 4345–55. http://dx.doi.org/10.3233/jifs-219225.
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Traditionally, a few activation functions have been considered in neural networks, including bounded functions such as threshold, sigmoidal and hyperbolic-tangent, as well as unbounded ReLU, GELU, and Soft-plus, among other functions for deep learning, but the search for new activation functions still being an open research area. In this paper, wavelets are reconsidered as activation functions in neural networks and the performance of Gaussian family wavelets (first, second and third derivatives) are studied together with other functions available in Keras-Tensorflow. Experimental results show how the combination of these activation functions can improve the performance and supports the idea of extending the list of activation functions to wavelets which can be available in high performance platforms.
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Randez-Gil, F., N. Bojunga, M. Proft, and K. D. Entian. "Glucose derepression of gluconeogenic enzymes in Saccharomyces cerevisiae correlates with phosphorylation of the gene activator Cat8p." Molecular and Cellular Biology 17, no. 5 (May 1997): 2502–10. http://dx.doi.org/10.1128/mcb.17.5.2502.
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The Cat8p zinc cluster protein is essential for growth of Saccharomyces cerevisiae with nonfermentable carbon sources. Expression of the CAT8 gene is subject to glucose repression mainly caused by Mig1p. Unexpectedly, the deletion of the Mig1p-binding motif within the CAT8 promoter did not increase CAT8 transcription; moreover, it resulted in a loss of CAT8 promoter activation. Insertion experiments with a promoter test plasmid confirmed that this regulatory 20-bp element influences glucose repression and derepression as well. This finding suggests an upstream activating function of this promoter region, which is Mig1p independent, as delta mig1 mutants are still able to derepress the CAT8 promoter. No other putative binding sites such as a Hap2/3/4/5p site and an Abf1p consensus site were functional with respect to glucose-regulated CAT8 expression. Fusions of Cat8p with the Gal4p DNA-binding domain mediated transcriptional activation. This activation capacity was still carbon source regulated and depended on the Cat1p (Snf1p) protein kinase, which indicated that Cat8p needs posttranslational modification to reveal its gene-activating function. Indeed, Western blot analysis on sodium dodecyl sulfate-gels revealed a single band (Cat8pI) with crude extracts from glucose-grown cells, whereas three bands (Cat8pI, -II, and -III) were identified in derepressed cells. Derepression-specific Cat8pII and -III resulted from differential phosphorylation, as shown by phosphatase treatment. Only the most extensively phosphorylated modification (Cat8pIII) depended on the Cat1p (Snf1p) kinase, indicating that another protein kinase is responsible for modification form Cat8pII. The occurrence of Cat8pIII was strongly correlated with the derepression of gluconeogenic enzymes (phosphoenolpyruvate carboxykinase and fructose-1,6-bisphosphatase) and gluconeogenic PCK1 mRNA. Furthermore, glucose triggered the dephosphorylation of Cat8pIII, but this did not depend on the Glc7p (Cid1p) phosphatase previously described as being involved in invertase repression. These results confirm our current model that glucose derepression of gluconeogenic genes needs Cat8p phosphorylation and additionally show that a still unknown transcriptional activator is also involved.
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Einspahr, K. J., R. T. Abraham, C. J. Dick, and P. J. Leibson. "Protein tyrosine phosphorylation and p56lck modification in IL-2 or phorbol ester-activated human natural killer cells." Journal of Immunology 145, no. 5 (September 1, 1990): 1490–97. http://dx.doi.org/10.4049/jimmunol.145.5.1490.
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Abstract Protein tyrosine kinases play fundamental roles in the transduction of signals that regulate cell growth, differentiation, and functional responses to a diversity of external stimuli. It is therefore likely that understanding protein tyrosine kinase activity in NK cells will be crucial in further defining the intracellular regulation of their unique and specialized functions. We investigated the role of protein tyrosine phosphorylation in receptor-mediated signal transduction using stimuli known to play major roles in regulating NK cell activation. Immunoblot analyses with antiphosphotyrosine antibodies demonstrated that IL-2, a potent stimulus for NK cell proliferation and an agent that enhances NK cytotoxic function, induced the tyrosine phosphorylation of at least eight proteins in clonal CD16+/CD3-human NK cells. In contrast, IL-4, which modulates NK cell function without inducing proliferation, had no apparent effect on protein tyrosine phosphorylation. Because protein kinase C (PKC) activation plays a prominent, yet distinct role in NK cell-mediated cytolytic reactions, we next investigated whether PKC activation affects NK cell protein tyrosine phosphorylation. Surprisingly, PKC-activating agents, including the phorbol esters 12-O-tetradecanoylphorbol-13-acetate and 4 beta-phorbol 12, 13-didecanoate, as well as the synthetic diacylglycerol,1-oleoyl-2-acetylglycerol, also induced the tyrosine phosphorylation of a distinct set of proteins. The 4 beta-phorbol 12,13-didecanoate homolog, 4 alpha-phorbol 12,13-didecanoate, which does not activate PKC, also failed to induce protein tyrosine phosphorylation. Further, the PKC inhibitor, 1-O-hexadecyl-2-O-methylglycerol blocked tyrosine phosphorylation induced by 1-oleoyl-2-acetylglycerol. In subsequent studies, both CD8+ and CD8- NK clones were found to express the src-family tyrosine kinase, p56lck, which was detected by immunoblot analysis with anti-p56lck antiserum. In both types of clonal NK cell lines, IL-2 and 12-O-tetradecanoyl-phorbol appeared to stimulate the differential phosphorylation of p56lck as evidenced by the appearance of higher molecular mass isoforms on SDS-polyacrylamide gels. Thus, our results identify and characterize a potential role for tyrosine phosphorylation and for the lymphocyte-specific tyrosine kinase p56lck in the signaling events that regulate NK cell activation.
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Tsuchida, Russell, Tim Pearce, Chris Van der Heide, Fred Roosta, and Marcus Gallagher. "Avoiding Kernel Fixed Points: Computing with ELU and GELU Infinite Networks." Proceedings of the AAAI Conference on Artificial Intelligence 35, no. 11 (May 18, 2021): 9967–77. http://dx.doi.org/10.1609/aaai.v35i11.17197.
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Analysing and computing with Gaussian processes arising from infinitely wide neural networks has recently seen a resurgence in popularity. Despite this, many explicit covariance functions of networks with activation functions used in modern networks remain unknown. Furthermore, while the kernels of deep networks can be computed iteratively, theoretical understanding of deep kernels is lacking, particularly with respect to fixed-point dynamics. Firstly, we derive the covariance functions of multi-layer perceptrons (MLPs) with exponential linear units (ELU) and Gaussian error linear units (GELU) and evaluate the performance of the limiting Gaussian processes on some benchmarks. Secondly, and more generally, we analyse the fixed-point dynamics of iterated kernels corresponding to a broad range of activation functions. We find that unlike some previously studied neural network kernels, these new kernels exhibit non-trivial fixed-point dynamics which are mirrored in finite-width neural networks. The fixed point behaviour present in some networks explains a mechanism for implicit regularisation in overparameterised deep models. Our results relate to both the static iid parameter conjugate kernel and the dynamic neural tangent kernel constructions
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Won, Sungyong, Tetsuro Ikegami, C. J. Peters, and Shinji Makino. "NSm Protein of Rift Valley Fever Virus Suppresses Virus-Induced Apoptosis." Journal of Virology 81, no. 24 (October 3, 2007): 13335–45. http://dx.doi.org/10.1128/jvi.01238-07.
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ABSTRACT Rift Valley fever virus (RVFV) is a member of the genus Phlebovirus within the family Bunyaviridae. It can cause severe epidemics among ruminants and fever, myalgia, a hemorrhagic syndrome, and/or encephalitis in humans. The RVFV M segment encodes the NSm and 78-kDa proteins and two major envelope proteins, Gn and Gc. The biological functions of the NSm and 78-kDa proteins are unknown; both proteins are dispensable for viral replication in cell cultures. To determine the biological functions of the NSm and 78-kDa proteins, we generated the mutant virus arMP-12-del21/384, carrying a large deletion in the pre-Gn region of the M segment. Neither NSm nor the 78-kDa protein was synthesized in arMP-12-del21/384-infected cells. Although arMP-12-del21/384 and its parental virus, arMP-12, showed similar growth kinetics and viral RNA and protein accumulation in infected cells, arMP-12-del21/384-infected cells induced extensive cell death and produced larger plaques than did arMP-12-infected cells. arMP-12-del21/384 replication triggered apoptosis, including the cleavage of caspase-3, the cleavage of its downstream substrate, poly(ADP-ribose) polymerase, and activation of the initiator caspases, caspase-8 and -9, earlier in infection than arMP-12. NSm expression in arMP-12-del21/384-infected cells suppressed the severity of caspase-3 activation. Further, NSm protein expression inhibited the staurosporine-induced activation of caspase-8 and -9, demonstrating that other viral proteins were dispensable for NSm's function in inhibiting apoptosis. RVFV NSm protein is the first identified Phlebovirus protein that has an antiapoptotic function.
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Yang, Xiaojuan, Surendranath Baliji, R. Cody Buchmann, Hui Wang, John A. Lindbo, Garry Sunter, and David M. Bisaro. "Functional Modulation of the Geminivirus AL2 Transcription Factor and Silencing Suppressor by Self-Interaction." Journal of Virology 81, no. 21 (August 22, 2007): 11972–81. http://dx.doi.org/10.1128/jvi.00617-07.
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ABSTRACT The DNA genomes of geminiviruses have a limited coding capacity that is compensated for by the production of small multifunctional proteins. The AL2 protein encoded by members of the genus Begomovirus (e.g., Tomato golden mosaic virus) is a transcriptional activator, a silencing suppressor, and a suppressor of a basal defense. The related L2 protein of Beet curly top virus (genus Curtovirus) shares the pathogenicity functions of AL2 but lacks transcriptional activation activity. It is known that AL2 and L2 can suppress local silencing by interacting with adenosine kinase (ADK) and can suppress basal defense by interacting with SNF1 kinase. However, how the activities of these viral proteins are regulated remains an unanswered question. Here, we provide some answers by demonstrating that AL2, but not L2, interacts with itself. The zinc finger-like motif (CCHC) is required but is not sufficient for AL2 self-interaction. Alanine substitutions for the invariant cysteine residues that comprise the motif abolish self-interaction or cause aberrant subnuclear localization but do not abolish interaction with ADK and SNF1. Using bimolecular fluorescence complementation, we show that AL2:AL2 complexes accumulate primarily in the nucleus, whereas AL2:ADK and L2:ADK complexes accumulate mainly in the cytoplasm. Further, the cysteine residue mutations impair the ability of AL2 to activate the coat protein promoter but do not affect local silencing suppression. Thus, AL2 self-interaction correlates with nuclear localization and efficient activation of transcription, whereas AL2 and L2 monomers can suppress local silencing by interacting with ADK in the cytoplasm.
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Brozna, J. P., N. F. Hauff, W. A. Phillips, and R. B. Johnston. "Activation of the respiratory burst in macrophages. Phosphorylation specifically associated with Fc receptor-mediated stimulation." Journal of Immunology 141, no. 5 (September 1, 1988): 1642–47. http://dx.doi.org/10.4049/jimmunol.141.5.1642.
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Abstract Inflammatory macrophages elicited from the peritoneal cavity of mice injected with endotoxin can avidly ingest E opsonized with IgG antibody (EIgG) or with IgM antibody and C (EIgMC). However, only ingestion of EIgG is associated with activation of the respiratory burst and release of superoxide anion. We compared the endogenous phosphorylation of proteins from macrophages stimulated by interaction with EIgG or EIgMC on the premise that proteins phosphorylated after stimulation by EIgG but not EIgMC could play a role in activating the enzyme (oxidase) responsible for the respiratory burst. Proteins were separated by one-dimensional and two-dimensional electrophoresis in polyacrylamide gels. We found that proteins with approximate Mr of 20 kDa, 23 kDa, 46 kDa, 48 kDa (three proteins), 67 kDa, and 130 kDa were more heavily phosphorylated after EIgG stimulation than after EIgMC stimulation. Exposure to PMA, which activates the respiratory burst oxidase, induced phosphorylation of the 23-kDa, 48-kDa group, and 130-kDa proteins that were phosphorylated after stimulation by EIgG. Activity of protein kinase C was found to be significantly increased in the particulate fraction of macrophages stimulated by EIgG but not in the particulate fraction of EIgMC-stimulated cells. These data are compatible with the hypotheses that phosphorylation of specific cellular proteins, especially with a Mr of approximately 48 kDa, is involved in activation of the respiratory burst oxidase, and that function of protein kinase C also plays a part in this activation process.
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Srividya, Narayanan, Iris Lange, Michael Hartmann, Qunrui Li, Maryam Mirzaei, and Bernd Markus Lange. "Biochemical characterization of acyl activating enzymes for side chain moieties of Taxol and its analogs." Journal of Biological Chemistry 295, no. 15 (February 20, 2020): 4963–73. http://dx.doi.org/10.1074/jbc.ra120.012663.
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Taxol (paclitaxel) is a very widely used anticancer drug, but its commercial sources mainly consist of stripped bark or suspension cultures of members of the plant genus Taxus. Taxol accumulates as part of a complex mixture of chemical analogs, termed taxoids, which complicates its production in pure form, highlighting the need for metabolic engineering approaches for high-level Taxol production in cell cultures or microbial hosts. Here, we report on the characterization of acyl-activating enzymes (AAEs) that catalyze the formation of CoA esters of different organic acids relevant for the N-substitution of the 3-phenylisoserine side chain of taxoids. On the basis of similarities to AAE genes of known function from other organisms, we identified candidate genes in publicly available transcriptome data sets obtained with Taxus × media. We cloned 17 AAE genes, expressed them heterologously in Escherichia coli, purified the corresponding recombinant enzymes, and performed in vitro assays with 27 organic acids as potential substrates. We identified TmAAE1 and TmAAE5 as the most efficient enzymes for the activation of butyric acid (Taxol D side chain), TmAAE13 as the best candidate for generating a CoA ester of tiglic acid (Taxol B side chain), TmAAE3 and TmAAE13 as suitable for the activation of 4-methylbutyric acid (N-debenzoyl-N-(2-methylbutyryl)taxol side chain), TmAAE15 as a highly efficient candidate for hexanoic acid activation (Taxol C side chain), and TmAAE4 as suitable candidate for esterification of benzoic acid with CoA (Taxol side chain). This study lays important groundwork for metabolic engineering efforts aimed at improving Taxol production in cell cultures.
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Zhang, Chuanhai, Junyu Liu, Xiaoyun He, Yao Sheng, Cui Yang, Haoyu Li, Jia Xu, Wentao Xu, and Kunlun Huang. "Caulis Spatholobi Ameliorates Obesity through Activating Brown Adipose Tissue and Modulating the Composition of Gut Microbiota." International Journal of Molecular Sciences 20, no. 20 (October 17, 2019): 5150. http://dx.doi.org/10.3390/ijms20205150.
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Obesity is associated with disrupted energy homeostasis and intestinal dysbiosis. Caulis Spatholobi, traditional Chinese medicine for herbal therapy, contains a wide range of bioactive compounds and has a specific pharmacological function. However, its effects on obesity and related metabolic disorder have remained largely unexplored. In this study, we showed that the water extract of Caulis Spatholobi (WECS) has a significant effect in inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, reducing insulin resistance and improving hepatic steatosis in diet-introduced obesity (DIO) mice. Besides, the administration of WECS significantly increased the expression levels of genes involved in the brown adipose tissue (BAT) activation and thermogenesis in DIO mice. Also, the activation of BAT treated with WECS was also confirmed in BAT primary cells. Mechanisms, the improvement of glucose homeostasis and insulin resistance may be related to the upregulated MAPK and AMPK pathways in white adipose tissue (WAT) and BAT. Notably, WECS also improved the obesity-induced gut microbiota dysbiosis, which induced an increase of anti-obesity and anti-diabetes related bacteria genus. In conclusion, Caulis Spatholobi can ameliorate obesity through activating brown adipose tissue and modulating the composition of gut microbiota. Our findings provide a novel perspective on Chinese medicine applications and provide a promising therapeutic approach for the treatment of obesity and metabolic disorders.
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HU, JUNFENG, XI YU, and YAFENG ZHAO. "BAMBOO DEFECT CLASSIFICATION BASED ON IMPROVED TRANSFORMER NETWORK." Wood Research 67, no. 3 (June 9, 2022): 501–10. http://dx.doi.org/10.37763/wr.1336-4561/67.3.501510.
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Deep learning-based methods, especially convolutional neural networks (CNNs), have shown their effectiveness for image classification. In this paper, vision transformer technology is used to classify the surface defects of processed bamboo, which can be more quick and accurate compared with the low efficiency of manual identification. In the first step, we replace the activation function from Gelu to Mish in the encoder part, but the classification performance is not satisfied. Then, to get a better classification results, we keep the original activation function and introduce the DropBlock. Compared with dropout, DropBlock can obtain better classification accuracy. Finally, compared with the results after transfer learning, it is proved that replacing dropout with DropBlock can improve the classification accuracy. The results on the bamboo chip datasets show that the accuracy of this method is 2% higher than the original transformer network whether using transfer learning.
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Perez-Quintero, Alvaro L., and Boris Szurek. "A Decade Decoded: Spies and Hackers in the History of TAL Effectors Research." Annual Review of Phytopathology 57, no. 1 (August 25, 2019): 459–81. http://dx.doi.org/10.1146/annurev-phyto-082718-100026.
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Transcription activator-like effectors (TALEs) from the genus Xanthomonas are proteins with the remarkable ability to directly bind the promoters of genes in the plant host to induce their expression, which often helps bacterial colonization. Metaphorically, TALEs act as spies that infiltrate the plant disguised as high-ranking civilians (transcription factors) to trick the plant into activating weak points that allow an invasion. Current knowledge of how TALEs operate allows researchers to predict their activity (counterespionage) and exploit their function, engineering them to do our bidding (a Manchurian agent). This has been possible thanks particularly to the discovery of their DNA binding mechanism, which obeys specific amino acid–DNA correspondences (the TALE code). Here, we review the history of how researchers discovered the way these proteins work and what has changed in the ten years since the discovery of the code. Recommended music for reading this review can be found in the Supplemental Material .
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Nakamura, K., C. J. Zhou, J. Parente, and C. S. Chew. "Parietal cell MAP kinases: multiple activation pathways." American Journal of Physiology-Gastrointestinal and Liver Physiology 271, no. 4 (October 1, 1996): G640—G649. http://dx.doi.org/10.1152/ajpgi.1996.271.4.g640.
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Epidermal growth factor (EGF) is a potent mitogen for many cell types; however, the best known effect of EGF on gastric parietal cell HCl secretion is inhibition of this response. Using rabbit parietal cells in primary culture, we recently showed that the effect of EGF is biphasic with acute inhibition followed by sustained enhancement of acid secretory-related responses. We hypothesized that EGF might activate a mitogen-activated protein (MAP) kinase signaling pathway in parietal cells, and this pathway might play a role in mediating sustained and/or acute effects of EGF on parietal cell acid secretory-related functions [C. S. Chew, K. Nakamura, and A. C. Petropolous. Am. J. Physiol. 267 (Gastrointest. Liver Physiol. 30): G818-G826, 1994]. We used several methodological approaches to demonstrate the presence of MAP kinase (MAPK) isoforms, extracellular signal-regulated kinases (ERKs) 1 and 2, in parietal cells and to begin to characterize their mechanisms of activation in this highly differentiated cell type. In acutely isolated, 90-98% enriched parietal cells, EGF biphasically activated ERK-1 and ERK-2, with peak response occurring at approximately 5 min followed by a sustained lower level of activation for at least 2 h. The EC50 for EGF (1.2 +/- 0.4 nM) was similar to the previously determined EC50 for the stimulatory effect of EGF on acid secretory responses. In contrast to EGF, the phorbol ester protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) induced a sustained activation of ERK-1 and ERK-2 for at least 2 h. Carbachol also activated ERK-1 and ERK-2; however, this response was weaker and monophasic. Neither the Ca2+ ionophore ionomycin nor the adenylyl cyclase activator forskolin altered basal or stimulated ERK activity. Carbachol, but not EGF or TPA, also activated an unidentified 70-kDa protein kinase as detected with in-gel myelin basic protein (MBP) kinase renaturation assays. Parietal cell MAPK activation was not correlated to a shift in apparent relative molecular mass on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels, suggesting that basal phosphorylation of ERK isoforms may be higher in parietal cells compared with actively proliferating cell lines. Also, in contrast to observations in neutrophils, the phosphatidylinositol 3-kinase (PtdIns 3-kinase) inhibitor, wortmannin (0.3-3 microM), failed to inhibit ERK activation in response to EGF, carbachol, or TPA. The combined data indicate that 1) EGF, TPA, and carbachol activate overlapping as well as distinct intracellular signaling pathways in gastric parietal cells, 2) EGF activates ERKs and enhances parietal cell acid secretory related functions via receptors with similar affinities, and 3) in contrast to some cell types, the parietal cell ERK-signaling cascade does not appear to be directly modulated by the PtdIns 3-kinase pathway or by elevated intracellular free Ca2+ or adenosine 3',5'-cyclic monophosphate concentrations.
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Guo, Chang-Jun, Wei-Jian Chen, Li-Qun Yuan, Li-Shi Yang, Shao-Ping Weng, Xiao-Qiang Yu, and Jian-Guo He. "The viral ankyrin repeat protein (ORF124L) from infectious spleen and kidney necrosis virus attenuates nuclear factor-κB activation and interacts with IκB kinase β." Journal of General Virology 92, no. 7 (July 1, 2011): 1561–70. http://dx.doi.org/10.1099/vir.0.031120-0.
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The ankyrin (ANK) repeat is one of the most common protein–protein interaction motifs, found predominantly in eukaryotes and bacteria, but the functions of the ANK repeat are rarely researched in animal viruses, with the exception of poxviruses. Infectious spleen and kidney necrosis virus (ISKNV) is a typical member of the genus Megalocytivirus in the family Iridoviridae and is a causative agent of epizootics in fish. The genome of ISKNV contains four putative viral ANK (vANK) repeat proteins and their functions remain largely unknown. In the present study, it was found that ORF124L, a vANK repeat protein in ISKNV, encodes a protein of 274 aa with three ANK repeats. Transcription of ORF124L was detected at 12 h post-infection (p.i.) and reached a peak at 40 h p.i. ORF124L was found to localize to both the nucleus and the cytoplasm in mandarin fish fry cells. ISKNV ORF124L interacted with the mandarin fish IκB kinase β protein (scIKKβ), and attenuated tumour necrosis factor alpha (TNF-α)- or phorbol myristate acetate (PMA)-induced activity of a nuclear factor κB (NF-κB)–luciferase reporter but did not interfere with the activity of an activator protein 1 (AP-1)–luciferase reporter. Phosphorylation of IκBα and nuclear translocation of NF-κB were also impaired by ISKNV ORF124L. In summary, ORF124L was identified as a vANK repeat protein and its role in inhibition of TNF-α-induced NF-κB signalling was investigated through interaction with the mandarin fish IKKβ. This work may help to improve our understanding of the function of fish iridovirus ANK repeat proteins.
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Zampara, Athina, Stephen J. Ahern, Yves Briers, Lone Brøndsted, and Martine Camilla Holst Sørensen. "Two Distinct Modes of Lysis Regulation in Campylobacter Fletchervirus and Firehammervirus Phages." Viruses 12, no. 11 (October 31, 2020): 1247. http://dx.doi.org/10.3390/v12111247.
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Campylobacter phages are divided into two genera; Fletchervirus and Firehammervirus, showing only limited intergenus homology. Here, we aim to identify the lytic genes of both genera using two representative phages (F352 and F379) from our collection. We performed a detailed in silico analysis searching for conserved protein domains and found that the predicted lytic genes are not organized into lysis cassettes but are conserved within each genus. To verify the function of selected lytic genes, the proteins were expressed in E. coli, followed by lytic assays. Our results show that Fletchervirus phages encode a typical signal peptide (SP) endolysin dependent on the Sec-pathway for translocation and a holin for activation. In contrast, Firehammervirus phages encode a novel endolysin that does not belong to currently described endolysin groups. This endolysin also uses the Sec-pathway for translocation but induces lysis of E. coli after overexpression. Interestingly, co-expression of this endolysin with an overlapping gene delayed and limited cell lysis, suggesting that this gene functions as a lysis inhibitor. These results indicate that Firehammervirus phages regulate lysis timing by a yet undescribed mechanism. In conclusion, we found that the two Campylobacter phage genera control lysis by two distinct mechanisms.
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Vicente-Soler, Jero, Teresa Soto, Alejandro Franco, José Cansado, and Marisa Madrid. "The Multiple Functions of Rho GTPases in Fission Yeasts." Cells 10, no. 6 (June 7, 2021): 1422. http://dx.doi.org/10.3390/cells10061422.
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The Rho family of GTPases represents highly conserved molecular switches involved in a plethora of physiological processes. Fission yeast Schizosaccharomyces pombe has become a fundamental model organism to study the functions of Rho GTPases over the past few decades. In recent years, another fission yeast species, Schizosaccharomyces japonicus, has come into focus offering insight into evolutionary changes within the genus. Both fission yeasts contain only six Rho-type GTPases that are spatiotemporally controlled by multiple guanine–nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and whose intricate regulation in response to external cues is starting to be uncovered. In the present review, we will outline and discuss the current knowledge and recent advances on how the fission yeasts Rho family GTPases regulate essential physiological processes such as morphogenesis and polarity, cellular integrity, cytokinesis and cellular differentiation.
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Dahiya, Satinder, Liqing Wang, Ulf H. Beier, Rongxiang Han, and Wayne W. Hancock. "HDAC10 Targeting Regulates Foxp3 Promoter, Enhances T-regulatory (Treg) Function and Suppresses Autoimmune Colitis." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 54.11. http://dx.doi.org/10.4049/jimmunol.200.supp.54.11.
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Abstract Targeting histone/protein deacetylases (HDACs), especially by isoform-selective targeting, has major promise as a means to enhance the function of Tregs and thereby suppress immune-related disorders, such as colitis. We present data on the functions of HDAC10 in Treg cells. We found that HDAC10 binds to the Foxp3 promoter in the Tregs, is able to physically bind and deacetylate Foxp3 (at K31), and regulates the transcriptional activity of the Foxp3 promoter. Next, we evaluated the function of HDAC10 using HDAC10 KO mice. Overall, such mice were healthy and HDAC10 deletion: (i) enhanced Treg suppressive function both in vitro (Treg suppression assays) and in vivo (homeostatic proliferation assays), compared to wild-type (WT) Tregs; (ii) modestly enhanced the stability of monomeric Foxp3 (reducing gels) but the oligomeric forms, which are more relevant functionally, were increased by more than two-fold (native gels); (iii) increased H3K4Me3 (activating) marks on Foxp3 promoter and the key regulatory region of Foxp3 promoter-CNS2; and (iv) enhanced binding of ATF/CREB and FoxO1 at the Foxp3 promoter and CNS2 sites. We then evaluated the effects of HDAC10 deletion in Tregs in colitis models using adoptively transferred Rag1 KO mice. We found that HDAC10 KO Tregs were superior to WT Tregs in: (i) a ‘prevention of induction’ model of colitis, whereby WT T effector cells were injected with a limiting ratio of Tregs that allowed for weight loss as an indicator of colitis; and (ii) rescuing from colitis. Studies to develop and test HDAC10-specific inhibitors are currently underway. Overall, we show that HDAC10 has a key role in Foxp3+ Treg cells, and is an important new target for therapeutic intervention in autoimmune diseases, including colitis.
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McPhillips, M. G., J. G. Oliveira, J. E. Spindler, R. Mitra, and A. A. McBride. "Brd4 Is Required for E2-Mediated Transcriptional Activation but Not Genome Partitioning of All Papillomaviruses." Journal of Virology 80, no. 19 (October 1, 2006): 9530–43. http://dx.doi.org/10.1128/jvi.01105-06.
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ABSTRACT Bromodomain protein 4 (Brd4) has been identified as the cellular binding target through which the E2 protein of bovine papillomavirus type 1 links the viral genome to mitotic chromosomes. This tethering ensures retention and efficient partitioning of genomes to daughter cells following cell division. E2 is also a regulator of viral gene expression and a replication factor, in association with the viral E1 protein. In this study, we show that E2 proteins from a wide range of papillomaviruses interact with Brd4, albeit with variations in efficiency. Moreover, disruption of the E2-Brd4 interaction abrogates the transactivation function of E2, indicating that Brd4 is required for E2-mediated transactivation of all papillomaviruses. However, the interaction of E2 and Brd4 is not required for genome partitioning of all papillomaviruses since a number of papillomavirus E2 proteins associate with mitotic chromosomes independently of Brd4 binding. Furthermore, mutations in E2 that disrupt the interaction with Brd4 do not affect the ability of these E2s to associate with chromosomes. Thus, while all papillomaviruses attach their genomes to cellular chromosomes to facilitate genome segregation, they target different cellular binding partners. In summary, the E2 proteins from many papillomaviruses, including the clinically important alpha genus human papillomaviruses, interact with Brd4 to mediate transcriptional activation function but not all depend on this interaction to efficiently associate with mitotic chromosomes.
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Sakurai, Tetsuya, Mutsuko Kukimoto-Niino, Kazufumi Kunimura, Nana Yamane, Daiji Sakata, Ryosuke Aihara, Tomoharu Yasuda, et al. "A conserved PI(4,5)P2–binding domain is critical for immune regulatory function of DOCK8." Life Science Alliance 4, no. 4 (February 11, 2021): e202000873. http://dx.doi.org/10.26508/lsa.202000873.
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DOCK8 is a Cdc42-specific guanine-nucleotide exchange factor that is essential for development and functions of various subsets of leukocytes in innate and acquired immune responses. Although DOCK8 plays a critical role in spatial control of Cdc42 activity during interstitial leukocyte migration, the mechanism remains unclear. We show that the DOCK homology region (DHR)-1 domain of DOCK8 binds specifically to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and is required for its recruitment to the plasma membrane. Structural and biochemical analyses reveal that DOCK8 DHR-1 domain consists of a C2 domain-like core with loops creating the upper surface pocket, where three basic residues are located for stereospecific recognition of phosphoinositides. Substitution of the two basic residues, K576 and R581, with alanine abolished PI(4,5)P2 binding in vitro, ablated the ability of DOCK8 to activate Cdc42 and support leukocyte migration in three-dimensional collagen gels. Dendritic cells carrying the mutation exhibited defective interstitial migration in vivo. Thus, our study uncovers a critical role of DOCK8 in coupling PI(4,5)P2 signaling with Cdc42 activation for immune regulation.
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Zhang, Nan, Xiangjian Zhang, Xiaoxia Liu, Hong Wang, Jing Xue, Jingying Yu, Ning Kang, and Xiaolu Wang. "Chrysophanol Inhibits NALP3 Inflammasome Activation and Ameliorates Cerebral Ischemia/Reperfusion in Mice." Mediators of Inflammation 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/370530.
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The most effective way to contain cerebral ischemic injury is reperfusion; however, reperfusion itself may result in tissue injury, for which inflammatory damage is one of the main causative factors. NALP3 inflammasome is a multiprotein complex. It consists of NALP3, ASC, and caspase-1, whose function is to switch on the inflammatory process. Chrysophanol is an extract from plants of Rheum genus and it possesses many pharmacological effects including its anti-inflammation activity. In this study, the effects of chrysophanol in cerebral ischemia/reperfusion and the potential mechanisms were investigated. Male CD1 mice were subject to transient middle cerebral artery occlusion (tMCAO). The NALP3 inflammasome activation status and its dynamic expression during the natural inflammatory response induced by tMCAO were first profiled. The neuroprotective effects of chrysophanol were then assessed and the potential mechanisms mediating the observed neuroprotection were then explored. Physical parameters including neurological deficit, infarct size, brain edema, and BBB permeability were measured at 24 h after tMCAO. Confocal microscopy, Western blotting, immunohistochemistry, and qRT-PCR techniques were utilized to analyze the expression of NALP3 inflammasome and IL-1β. Our results indicated that the brain tissue damage during cerebral ischemia/reperfusion is accompanied by NALP3 inflammasome activation. Chrysophanol could inhibit the activation of NALP3 inflammasome and protect cerebral ischemic stroke.
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Ilhan, Zehra Esra, Paweł Łaniewski, Adriana Tonachio, and Melissa M. Herbst-Kralovetz. "Members of Prevotella Genus Distinctively Modulate Innate Immune and Barrier Functions in a Human Three-Dimensional Endometrial Epithelial Cell Model." Journal of Infectious Diseases 222, no. 12 (June 9, 2020): 2082–92. http://dx.doi.org/10.1093/infdis/jiaa324.
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Abstract Background Prevotella species are commonly isolated from the reproductive tract of women with obstetric/gynecologic health complications. However, contributions of this genus to changes in local microenvironment are not well characterized. Our objective was to evaluate species-specific effects of Prevotella on the human endometrial epithelium. Methods Thirteen Prevotella strains, originally isolated from the human oral cavity, amniotic fluid, endometrium, or vagina (including women with bacterial vaginosis), were obtained from BEI and ATCC resources. Bacteria were evaluated in silico and in vitro using human endometrial epithelial cells (EEC) grown as monolayers or a 3-dimensional (3D) model. Results Genomic characterization illustrated metabolic and phylogenetic diversity of Prevotella genus. Among tested species, P. disiens exhibited cytotoxicity. Scanning electron microscopy analysis of the 3D EEC model revealed species-specific colonization patterns and alterations of ultracellular structures. Infection with sialidase-producing P. timonensis resulted in elongated microvilli, and increased MUC3 and MUC4 expression. Infections with Prevotella species, including P. bivia, did not result in significant proinflammatory activation of EEC. Conclusions Collectively, findings indicate that Prevotella species are metabolically diverse and overall not cytotoxic or overtly inflammatory in EEC; however, these bacteria can form biofilms, alter barrier properties of the endometrial epithelium, and ultimately impact colonization of secondary colonizers.
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Manville, Rían W., Jennifer van der Horst, Kaitlyn E. Redford, Benjamin B. Katz, Thomas A. Jepps, and Geoffrey W. Abbott. "KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines." Proceedings of the National Academy of Sciences 116, no. 42 (September 30, 2019): 21236–45. http://dx.doi.org/10.1073/pnas.1907511116.
Full textAbstract:
Botanical folk medicines have been used throughout human history to treat common disorders such as hypertension, often with unknown underlying mechanisms. Here, we discovered that hypotensive folk medicines from a genetically diverse range of plant species each selectively activated the vascular-expressed KCNQ5 potassium channel, a feature lacking in the modern synthetic pharmacopeia, whereas nonhypotensive plant extracts did not. Analyzing constituents of the hypotensive Sophora flavescens root, we found that the quinolizidine alkaloid aloperine is a KCNQ-dependent vasorelaxant that potently and isoform-selectively activates KCNQ5 by binding near the foot of the channel voltage sensor. Our findings reveal that KCNQ5-selective activation is a defining molecular mechanistic signature of genetically diverse traditional botanical hypotensives, transcending plant genus and human cultural boundaries. Discovery of botanical KCNQ5-selective potassium channel openers may enable future targeted therapies for diseases including hypertension and KCNQ5 loss-of-function encephalopathy.
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Scherer, Mario, Huijun Wei, Ralf Liese, and Reinhard Fischer. "Aspergillus nidulans Catalase-Peroxidase Gene (cpeA) Is Transcriptionally Induced during Sexual Development through the Transcription Factor StuA." Eukaryotic Cell 1, no. 5 (October 2002): 725–35. http://dx.doi.org/10.1128/ec.1.5.725-735.2002.
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ABSTRACT Catalases, peroxidases, and catalase-peroxidases are important enzymes to cope with reactive oxygen species in pro- and eukaryotic cells. In the filamentous fungus Aspergillus nidulans three monofunctional catalases have been described, and a fourth catalase activity was observed in native polyacrylamide gels. The latter activity is probably due to the bifunctional enzyme catalase-peroxidase, which we characterized here. The gene, named cpeA, encodes an 81-kDa polypeptide with a conserved motif for heme coordination. The enzyme comprises of two similar domains, suggesting gene duplication and fusion during evolution. The first 439 amino acids share 22% identical residues with the C terminus. Homologous proteins are found in several prokaryotes, such as Escherichia coli and Mycobacterium tuberculosis (both with 61% identity). In fungi the enzyme has been noted in Penicillium simplicissimum, Septoria tritici, and Neurospora crassa (69% identical amino acids) but is absent from Saccharomyces cerevisiae. Expression analysis in A. nidulans revealed that the gene is transcriptionally induced upon carbon starvation and during sexual development, but starvation is not sufficient to reach high levels of the transcript during development. Besides transcriptional activation, we present evidence for posttranscriptional regulation. A green fluorescent protein fusion protein localized to the cytoplasm of Hülle cells. The Hülle cell-specific expression was dependent on the developmental regulator StuA, suggesting an activating function of this helix-loop-helix transcription factor.
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Kee, Matthew F., Yongzhi Qiu, David R. Myers, Yumiko Sakurai, and Wilbur A. Lam. "Platelet Mechanosensing of Collagen Matrices." Blood 124, no. 21 (December 6, 2014): 1437. http://dx.doi.org/10.1182/blood.v124.21.1437.1437.
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Abstract Background: Vascular injury causes platelets to initiate hemostasis by first adhering to exposed subendothelial matrix proteins such as collagen. While the biochemical and biological aspects of platelet adhesion via collagen and von willebrand factor are well characterized, if and whether the mechanical properties of the subendothelial matrix affect platelet function is relatively unknown. As purely mechanical cues, such as substrate stiffness, from collagen matrices are sensed and transduced by endothelial cells to alter their physiological processes, platelets may also exhibit similar behavior (Chein S., AM J Physiol Heart Circ Physiol, 2007). In addition, recent reports demonstrate that the stiffness of the subendothelium varies in different disease states, including atherosclerosis and changes associated with aging (Stroka KM & Aranda-Espinoza H, Blood, 2011). Therefore, understanding the effect of subendothelium stiffness on platelet adhesion, spreading, and activation will provide insight into how biomechanical and biochemical factors interact during clot formation in health and disease. To that end, we fabricated polyacrylamide (PA) gels of varying stiffnesses covalently conjugated with collagen to model the biomechanical properties of the subendothelium. Via differential crosslinking, the stiffness of these PA gels can be varied while maintaining constant collagen concentrations on the gel surface, enabling decoupling of mechanical and biochemical cues (Lam, et al, Mol Cancer, 2010; Pathak A & Kumar S, P Natl Acad Sci, 2012). With these systems, we investigated how the stiffness of the underlying collagen matrix affects platelet adhesion, spreading and activation under static and flow conditions and used pharmacological cytoskeletal inhibitors to investigate the underlying mechanotransductive mechanisms. Results and Discussions: Type I collagen was covalently conjugated to the surface of PA gels with varying substrate stiffnesses (0.25 to 100 kilopascals (kPa)); the range of vessel wall stiffness in vivo. The PA gels were then incubated with 5.5 x 106 platelets/ml for 1 hour and stained with a fluorescent membrane dye. While collagen substrate stiffness did not affect platelet adhesion, determined by the number of platelets on each gel, significant differences were observed in platelet spreading area on collagen-conjugated PA gels with stiffnesses >2.5 kPa compared to PA gels of <2.5 kPa (Fig. 1A and 1B). Using PAC-1-FITC and Annexin-V-AF488 to measure platelet integrin αIIbβ3 activation and platelet phosphatidylserine (PS) exposure, respectively, we found that varying the substrate stiffness of collagen matrices did not affect αIIbβ3 activation on adherent platelets but did result in differential levels of PS exposure on adherent platelets, with increased PS exposure on stiffer PA gels (Fig. 1C). In addition, using the myosin light chain kinase (MLCK) inhibitor ML-7 and the Rho kinase inhibitor Y-27632, we observed that platelet exposure to ML-7 eliminated the substrate stiffness-mediated effect on platelet spreading as platelet spreading on PA gels stiffer than 5 kPa was decreased to the levels of that on soft PA gels of 0.5 kPa. Y-27632 exposure did not cause a similar effect, as platelet spreading was increased for all stiffness conditions (Fig. 1D). Finally, under flow conditions using a shear rate of 150 s-1, platelet adhesion in addition to platelet spreading was mediated by substrate stiffness (Fig. 1E); possibly due to weaker collagen attachment on softer substrates that cannot sufficiently resist drag forces. Conclusion: Our results indicate that platelets adhered on collagen mechanosense the stiffness of the underlying subendothelial substrate and transduce these cues into differential levels of adhesion, spreading and activation. While MLCK mediates aspects of this process, further mechanistic studies are currently being conducted. In addition, as shear stress might interact with the observed substrate stiffness-mediated phenomenon, additional experiments under flow at different shear rates are also ongoing. Disclosures No relevant conflicts of interest to declare.
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Li, W., and J. Schlessinger. "Platelet-derived growth factor (PDGF)-induced disulfide-linked dimerization of PDGF receptor in living cells." Molecular and Cellular Biology 11, no. 7 (July 1991): 3756–61. http://dx.doi.org/10.1128/mcb.11.7.3756-3761.1991.
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It is well established that epidermal growth factor and platelet-derived growth factor (PDGF) are able to induce noncovalent dimerization of their surface receptors. It is thought that receptor dimerization plays an important role in activation of the tyrosine kinase function and in the process of receptor autophosphorylation. Here we show that the addition of either PDGF-BB or PDGF-AA to intact 3T3 cells induces formation of 400- and 430-kDa species, respectively, recognized by either anti-PDGF receptor antibodies or anti-phosphotyrosine antibodies. Interestingly, the 400- and the 430-kDa species are detected in nonreducing gels but not in reducing gels. Moreover, an alkylating agent, N-ethylmaleimide, inhibits PDGF-induced formation of high-molecular-mass species. Comparisons of V8 protease peptide maps of [35S]methionine-labeled PDGF receptors and high-molecular-mass proteins indicate that they represent dimers of PDGF receptors. It appears therefore that in addition to noncovalent dimerization, PDGF receptors undergo ligand-dependent disulfide-linked dimerization.
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Li, W., and J. Schlessinger. "Platelet-derived growth factor (PDGF)-induced disulfide-linked dimerization of PDGF receptor in living cells." Molecular and Cellular Biology 11, no. 7 (July 1991): 3756–61. http://dx.doi.org/10.1128/mcb.11.7.3756.
Full textAbstract:
It is well established that epidermal growth factor and platelet-derived growth factor (PDGF) are able to induce noncovalent dimerization of their surface receptors. It is thought that receptor dimerization plays an important role in activation of the tyrosine kinase function and in the process of receptor autophosphorylation. Here we show that the addition of either PDGF-BB or PDGF-AA to intact 3T3 cells induces formation of 400- and 430-kDa species, respectively, recognized by either anti-PDGF receptor antibodies or anti-phosphotyrosine antibodies. Interestingly, the 400- and the 430-kDa species are detected in nonreducing gels but not in reducing gels. Moreover, an alkylating agent, N-ethylmaleimide, inhibits PDGF-induced formation of high-molecular-mass species. Comparisons of V8 protease peptide maps of [35S]methionine-labeled PDGF receptors and high-molecular-mass proteins indicate that they represent dimers of PDGF receptors. It appears therefore that in addition to noncovalent dimerization, PDGF receptors undergo ligand-dependent disulfide-linked dimerization.
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Buckley, Bradley A., Marie-Eve Owen, and Gretchen E. Hofmann. "Adjusting the thermostat: the threshold induction temperature for the heat-shock response in intertidal mussels (genus Mytilus) changes as a function of thermal history." Journal of Experimental Biology 204, no. 20 (October 15, 2001): 3571–79. http://dx.doi.org/10.1242/jeb.204.20.3571.
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SUMMARY Spatio-temporal variation in heat-shock gene expression gives organisms the ability to respond to changing thermal environments. The temperature at which heat-shock genes are induced, the threshold induction temperature, varies as a function of the recent thermal history of an organism. To elucidate the mechanism by which this plasticity in gene expression is achieved, we determined heat-shock protein (Hsp) induction threshold temperatures in the intertidal mussel Mytilus trossulus collected from the field in February and again in August. In a separate experiment, threshold induction temperatures, endogenous levels of both the constitutive and inducible isoforms of Hsps from the 70 kDa family and the quantity of ubiquitinated proteins (a measure of cellular protein denaturation) were measured in M. trossulus after either 6 weeks of cold acclimation in the laboratory or acclimatization to warm, summer temperatures in the field over the same period. In addition, we quantified levels of activated heat-shock transcription factor 1 (HSF1) in both groups of mussels (HSF1 inducibly transactivates all classes of Hsp genes). Lastly, we compared the temperature of HSF1 activation with the induction threshold temperature in the congeneric M. californianus. It was found that the threshold induction temperature in M. trossulus was 23°C in February and 28°C in August. This agreed with the acclimation/acclimatization experiment, in which mussels acclimated in seawater tables to a constant temperature of 10–11°C for 6 weeks displayed a threshold induction temperature of 20–23°C compared with 26–29°C for individuals that were experiencing considerably warmer body temperatures in the intertidal zone over the same period. This coincided with a significant increase in the inducible isoform of Hsp70 in warm-acclimatized individuals but no increase in the constitutive isoform or in HSF1. Levels of ubiquitin-conjugated protein were significantly higher in the field mussels than in the laboratory-acclimated individuals. Finally, the temperature of HSF1 activation in M. californianus was found to be approximately 9°C lower than the induction threshold for this species.
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Urbano, Rebecca Lownes, Swathi Swaminathan, and Alisa Morss Clyne. "Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation." Applied Bionics and Biomechanics 2019 (April 14, 2019): 1–14. http://dx.doi.org/10.1155/2019/6578492.
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Arterial stiffness, which increases with aging and hypertension, is an independent cardiovascular risk factor. While stiffer substrates are known to affect single endothelial cell morphology and migration, the effect of substrate stiffness on endothelial monolayer function is less understood. The objective of this study was to determine if substrate stiffness increased endothelial monolayer reactive oxygen species (ROS) in response to protein kinase C (PKC) activation and if this oxidative stress then impacted adherens junction integrity. Porcine aortic endothelial cells were cultured on varied stiffness polyacrylamide gels and treated with phorbol 12-myristate 13-acetate (PMA), which stimulates PKC and ROS without increasing actinomyosin contractility. PMA-treated endothelial cells on stiffer substrates increased ROS and adherens junction loss without increased contractility. ROS scavengers abrogated PMA effects on cell-cell junctions, with a more profound effect in cells on stiffer substrates. Finally, endothelial cells in aortae from elastin haploinsufficient mice (Eln+/-), which were stiffer than aortae from wild-type mice, showed decreased VE-cadherin colocalization with peripheral actin following PMA treatment. These data suggest that oxidative stress may be enhanced in endothelial cells in stiffer vessels, which could contribute to the association between arterial stiffness and cardiovascular disease.
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Nayak, Ramnath, and David J. Pintel. "Adeno-Associated Viruses Can Induce Phosphorylation of eIF2α via PKR Activation, Which Can Be Overcome by Helper Adenovirus Type 5 Virus-Associated RNA." Journal of Virology 81, no. 21 (August 22, 2007): 11908–16. http://dx.doi.org/10.1128/jvi.01132-07.
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ABSTRACT Mutants of adenovirus type 5 (Ad5) virus-associated RNA I deficient in inhibiting the activation and subsequent phosphorylation of protein kinase R (PKR) could neither function as helpers for adeno-associated virus type 5 (AAV5) replication nor enhance AAV5 protein accumulation in either the presence or absence of Ad5 E4Orf6 and E2a. Furthermore, a short region of the AAV5 capsid gene RNA leader sequence surrounding the AUG of VP1 could induce the phosphorylation of eIF2α. Both short interfering RNA directed against PKR and the addition of the herpes simplex virus ICP34.5 protein enhanced the accumulation of AAV5 capsid protein in the presence of the AAV5 capsid gene PKR-inducing element, suggesting that VA RNA acted to overcome direct AAV5-induced activation of PKR that led to the phosphorylation of eIF2α. The expression of both the closely related goat-derived AAV and the prototype AAV2 capsid gene transcription units also induced the phosphorylation of eIF2α, suggesting that the induction of the PKR/eIF2α cellular response may be a previously unrecognized general feature of at least the Dependovirus genus of the Parvovirinae.
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Tolg, Cornelia, Sara R. Hamilton, Kerry-Ann Nakrieko, Fatemeh Kooshesh, Paul Walton, James B. McCarthy, Mina J. Bissell, and Eva A. Turley. "Rhamm−/− fibroblasts are defective in CD44-mediated ERK1,2 motogenic signaling, leading to defective skin wound repair." Journal of Cell Biology 175, no. 6 (December 11, 2006): 1017–28. http://dx.doi.org/10.1083/jcb.200511027.
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Rhamm (receptor for hyaluronan-mediated motility) is an hyaluronan binding protein with limited expression in normal tissues and high expression in advanced cancers. To understand its physiological functions and identify the molecular mechanisms underlying these functions, we created mice with a genetic deletion of Rhamm. We show that Rhamm−/− fibroblasts fail to resurface scratch wounds >3 mm or invade hyaluronan-supplemented collagen gels in culture. We identify a requirement for Rhamm in the localization of CD44 to the cell surface, formation of CD44–ERK1,2 (extracellular-regulated kinase 1,2) complexes, and activation/subcellular targeting of ERK1,2 to the cell nucleus. We also show that cell surface Rhamm, restricted to the extracellular compartment by linking recombinant protein to beads, and expression of mutant active mitogen-activated kinase kinase 1 (Mek1) are sufficient to rescue aberrant signaling through CD44–ERK1,2 complexes in Rh−/− fibroblasts. ERK1,2 activation and fibroblast migration/differentiation is also defective during repair of Rh−/− excisional skin wounds and results in aberrant granulation tissue in vivo. These results identify Rhamm as an essential regulator of CD44–ERK1,2 fibroblast motogenic signaling required for wound repair.
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Lafleur, Marc A., Daosong Xu, and Martin E. Hemler. "Tetraspanin Proteins Regulate Membrane Type-1 Matrix Metalloproteinase-dependent Pericellular Proteolysis." Molecular Biology of the Cell 20, no. 7 (April 2009): 2030–40. http://dx.doi.org/10.1091/mbc.e08-11-1149.
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Membrane type-1 matrix metalloproteinase (MT1-MMP) supports tumor cell invasion through extracellular matrix barriers containing fibrin, collagen, fibronectin, and other proteins. Here, we show that simultaneous knockdown of two or three members of the tetraspanin family (CD9, CD81, and TSPAN12) markedly decreases MT1-MMP proteolytic functions in cancer cells. Affected functions include fibronectin proteolysis, invasion and growth in three-dimensional fibrin and collagen gels, and MMP-2 activation. Tetraspanin proteins (CD9, CD81, and TSPAN2) selectively coimmunoprecipitate and colocalize with MT1-MMP. Although tetraspanins do not affect the initial biosynthesis of MT1-MMP, they do protect the newly synthesized protein from lysosomal degradation and support its delivery to the cell surface. Interfering with MT1-MMP-tetraspanin collaboration may be a useful therapeutic approach to limit cancer cell invasion and metastasis.
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Rascher, Monique, Kathrin Wittstein, Barbara Winter, Zeljka Rupcic, Alexandra Wolf-Asseburg, Marc Stadler, and Reinhard W. Köster. "Erinacine C Activates Transcription from a Consensus ETS DNA Binding Site in Astrocytic Cells in Addition to NGF Induction." Biomolecules 10, no. 10 (October 14, 2020): 1440. http://dx.doi.org/10.3390/biom10101440.
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Medicinal mushrooms of the genus Hericium are known to produce secondary metabolites with homeostatic properties for the central nervous system. We and others have recently demonstrated that among these metabolites cyathane diterpenoids and in particular erinacine C possess potent neurotrophin inducing properties in astrocytic cells. Yet, the signaling events downstream of erinacine C induced neurotrophin acitivity in neural-like adrenal phaeochromocytoma cells (PC12) cells have remained elusive. Similar, signaling events activated by erinacine C in astrocytic cells are unknown. Using a combination of genetic and pharmacological inhibitors we show that erinacine C induced neurotrophic activity mediates PC12 cell differentiation via the TrkA receptor and likely its associated PLCγ-, PI3K-, and MAPK/ERK pathways. Furthermore, a small library of transcriptional activation reporters revealed that erinacine C induces transcriptional activation mediated by DNA consensus binding sites of selected conserved transcription factor families. Among these, transcription is activated from an ETS consensus in a concentration dependent manner. Interestingly, induced ETS-consensus transcription occurs in parallel and independent of neurotrophin induction. This finding helps to explain the many pleiotropic functions of cyathane diterpenoids. Moreover, our studies provide genetic access to cyathane diterpenoid functions in astrocytic cells and help to mechanistically understand the action of cyathanes in glial cells.
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Schilling, Jennifer, Karin Wagner, Stephanie Seekircher, Lilo Greune, Verena Humberg, M. Alexander Schmidt, and Gerhard Heusipp. "Transcriptional Activation of the tad Type IVb Pilus Operon by PypB in Yersinia enterocolitica." Journal of Bacteriology 192, no. 14 (May 14, 2010): 3809–21. http://dx.doi.org/10.1128/jb.01672-09.
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ABSTRACT Type IV pili are virulence factors in various bacteria and mediate, among other functions, the colonization of diverse surfaces. Various subclasses of type IV pili have been identified, but information on pilus expression, biogenesis, and the associated phenotypes is sparse for the genus Yersinia. We recently described the identification of PypB as a transcriptional regulator in Yersinia enterocolitica. Here we show that the pypB gene is associated with the tad locus, a genomic island that is widespread among bacterial and archaeal species. The genetic linkage of pypB with the tad locus is conserved throughout the yersiniae but is not found among other bacteria carrying the tad locus. We show that the genes of the tad locus form an operon in Y. enterocolitica that is controlled by PypB and that pypB is part of this operon. The tad genes encode functions necessary for the biogenesis of the Flp subfamily of type IVb pili initially described for Aggregatibacter actinomycetemcomitans to mediate a tight-adherence phenotype. In Y. enterocolitica, the Flp pilin protein shows some peculiarities in its amino acid sequence that imply similarities as well as differences compared to typical motifs found in the Flp subtype of type IVb pili. Flp is expressed and processed after PypB overproduction, resulting in microcolony formation but not in increased adherence to biotic or abiotic surfaces. Our data describe the transcriptional regulation of the tad type IVb pilus operon by PypB in Y. enterocolitica but fail to show most previously described phenotypes associated with this type of pilus in other bacteria.
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Fialka, I., H. Schwarz, E. Reichmann, M. Oft, M. Busslinger, and H. Beug. "The estrogen-dependent c-JunER protein causes a reversible loss of mammary epithelial cell polarity involving a destabilization of adherens junctions." Journal of Cell Biology 132, no. 6 (March 15, 1996): 1115–32. http://dx.doi.org/10.1083/jcb.132.6.1115.
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Members of the epidermal growth factor (EGF) receptor family are known to be specifically involved in mammary carcinogenesis. As a nuclear target of activated receptors, we examined c-Jun in mammary epithelial cells. For this, we used a c-JunER fusion protein which was tightly controlled by estrogen. Activation of the JunER by hormone resulted in the transcriptional regulation of a variety of AP-1 target genes. Hormone-activated JunER induced the loss of epithelial polarity, a disruption of intercellular junctions and normal barrier function and the formation of irregular multilayers. These changes were completely reversible upon hormone withdrawal. Loss of epithelial polarity involved redistribution of both apical and basolateral proteins to the entire plasma membrane. The redistribution of E-cadherin and beta-catenin was accompanied by a destabilization of complexes formed between these two proteins, leading to an enrichment of beta-catenin in the detergent-soluble fraction. Uninduced cells were able to form three-dimensional tubular structures in collagen I gels which were disrupted upon JunER activation, leading to irregular cell aggregates. The JunER-induced disruption of tubular structures was dependent on active signaling by growth factors. Moreover, the effects of JunER could be mimicked in normal cells by the addition of acidic fibroblast growth factor (aFGF). These data suggest that a possible function of c-Jun in epithelial cells is to modulate epithelial polarity and regulate tissue organization, processes which may be equally important for both normal breast development and as initiating steps in carcinogenesis.
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Kamio, Koichiro, Tadashi Sato, Xiangde Liu, Hisatoshi Sugiura, Shinsaku Togo, Tetsu Kobayashi, Shin Kawasaki, et al. "Prostacyclin analogs stimulate VEGF production from human lung fibroblasts in culture." American Journal of Physiology-Lung Cellular and Molecular Physiology 294, no. 6 (June 2008): L1226—L1232. http://dx.doi.org/10.1152/ajplung.00129.2007.
Full textAbstract:
Prostacyclin is a short-lived metabolite of arachidonic acid that is produced by several cells in the lung and prominently by endothelial cells. It increases intracellular cAMP levels activating downstream signaling thus regulating vascular mesenchymal cell functions. The alveolar wall contains a rich capillary network as well as a population of mesenchymal cells, i.e., fibroblasts. The current study evaluated the hypothesis that prostacyclin may mediate signaling between endothelial and mesenchymal cells in the alveolar wall by assessing the ability of prostacyclin analogs to modulate fibroblast release of VEGF. To accomplish this study, human lung fibroblasts were cultured in routine culture on plastic support and in three-dimensional collagen gels with or without three prostacyclin analogs, carbaprostacyclin, iloprost, and beraprost, and the production of VEGF was evaluated by ELISA and quantitative real-time PCR. Iloprost and beraprost significantly stimulated VEGF mRNA levels and protein release in a concentration-dependent manner. These effects were blocked by the adenylate cyclase inhibitor SQ-22536 and by the protein kinase A (PKA) inhibitor KT-5720 and were reproduced by a direct PKA activator but not by an activator of exchange protein directly activated by cAMP (Epac), indicating that cAMP-activated PKA signaling mediated the effect. Since VEGF serves to maintain the pulmonary microvasculature, the current study suggests that prostacyclin is part of a bidirectional signaling network between the mesenchymal and vascular cells of the alveolar wall. Prostacyclin analogs, therefore, have the potential to modulate the maintenance of the pulmonary microcirculation by driving the production of VEGF from lung fibroblasts.
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Zou, Li, and Haowen Cheng. "Research on Wind Turbine Blade Surface Damage Identification Based on Improved Convolution Neural Network." Applied Sciences 12, no. 18 (September 18, 2022): 9338. http://dx.doi.org/10.3390/app12189338.
Full textAbstract:
Wind turbine blades are easily affected by the working environment and often show damage features such as cracks and surface shedding. An improved convolution neural network, ED Net, is proposed to identify their damage features. An EAC block based on the improved asymmetric convolution is introduced which strengthens the feature extraction during convolution. A DPCI_SC block, which is improved based on the attention module, is embedded to enhance the ability to obtain spatial location information of the damage. GELU is used as the activation function. The loss function is smoothed and labeled during training. Finally, three sets of experiments were conducted. Experiment 1 confirmed the efficacy of the ED Net for identifying damaged wind turbine blades. Experiment 2 confirmed the efficacy of the relevant improvements proposed in this work. Experiment 3 compares the recognition of wind turbine blade damage by commonly used lightweight networks and shows that the ED Net model proposed has a better performance with an accuracy range of 99.12% to 99.23% and a recall of 99.23%
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Raj, G. V., and K. Khalili. "Identification and characterization of a novel GGA/C-binding protein, GBP-i, that is rapidly inducible by cytokines." Molecular and Cellular Biology 14, no. 12 (December 1994): 7770–81. http://dx.doi.org/10.1128/mcb.14.12.7770-7781.1994.
Full textAbstract:
Immunosuppressive states with accompanying alterations in cytokine profiles have been postulated to play a vital role in the reactivation of viruses from latency. Cytokines regulate gene expression by activating transcription factors via well-characterized signal transduction pathways. In this study, we report the identification of a novel inducible protein, GBP-i, that binds to a double-stranded GGA/C-rich region of the transcriptional control region of the human papovavirus JC virus (JCV), specifically within the origin of viral DNA replication. GBP-i is distinct from previously characterized GC-box-binding proteins with respect to both its sequence specificity and its electrophoretic mobility on native and denaturing gels. GBP-i responds within 90 min to phorbol myristate acetate stimulation; however, unlike typical phorbol myristate acetate-inducible factors, this rapid induction is regulated primarily at the transcriptional level. Further, the induction of GBP-i appears to be widespread and mediated by many inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, gamma interferon, and transforming growth factor beta. Interestingly, the induced protein acts as a transcriptional repressor in its native context in the JCVL promoter. However, when its binding sequence is transposed to a heterologous promoter, GBP-i appears to function as a transcriptional activator. The data presented here suggest a role for GBP-i in cytokine-mediated induction of viral and cellular genes.
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Raj, G. V., and K. Khalili. "Identification and characterization of a novel GGA/C-binding protein, GBP-i, that is rapidly inducible by cytokines." Molecular and Cellular Biology 14, no. 12 (December 1994): 7770–81. http://dx.doi.org/10.1128/mcb.14.12.7770.
Full textAbstract:
Immunosuppressive states with accompanying alterations in cytokine profiles have been postulated to play a vital role in the reactivation of viruses from latency. Cytokines regulate gene expression by activating transcription factors via well-characterized signal transduction pathways. In this study, we report the identification of a novel inducible protein, GBP-i, that binds to a double-stranded GGA/C-rich region of the transcriptional control region of the human papovavirus JC virus (JCV), specifically within the origin of viral DNA replication. GBP-i is distinct from previously characterized GC-box-binding proteins with respect to both its sequence specificity and its electrophoretic mobility on native and denaturing gels. GBP-i responds within 90 min to phorbol myristate acetate stimulation; however, unlike typical phorbol myristate acetate-inducible factors, this rapid induction is regulated primarily at the transcriptional level. Further, the induction of GBP-i appears to be widespread and mediated by many inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, gamma interferon, and transforming growth factor beta. Interestingly, the induced protein acts as a transcriptional repressor in its native context in the JCVL promoter. However, when its binding sequence is transposed to a heterologous promoter, GBP-i appears to function as a transcriptional activator. The data presented here suggest a role for GBP-i in cytokine-mediated induction of viral and cellular genes.
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Yang, Qing, Shukai Duan, and Lidan Wang. "Efficient Identification of Apple Leaf Diseases in the Wild Using Convolutional Neural Networks." Agronomy 12, no. 11 (November 9, 2022): 2784. http://dx.doi.org/10.3390/agronomy12112784.
Full textAbstract:
Efficient identification of apple leaf diseases (ALDs) can reduce the use of pesticides and increase the quality of apple fruit, which is of significance to smart agriculture. However, existing research into identifying ALDs lacks models/methods that satisfy efficient identification in the wild environment, hindering the application of smart agriculture in the apple industry. Therefore, this paper explores an ACCURATE, LIGHTWEIGHT, and ROBUST convolutional neural network (CNN) called EfficientNet-MG, improving the conventional EfficientNet network by the multistage feature fusion (MSFF) method and gaussian error linear unit (GELU) activation function. The shallow and deep convolutional layers usually contain detailed and semantic information, respectively, but conventional EfficientNets do not fully utilize the different stage convolutional layers. Thus, MSFF was adopted to improve the semantic representation capacity of the last layer of features, and GELU was used to adapt to complicated tasks. Further, a comprehensive ALD dataset called AppleLeaf9 was constructed for the wild environment. The experimental results show that EfficientNet-MG achieves a higher accuracy (99.11%) and fewer parameters (8.42 M) than the five classical CNN models, thus proving that EfficientNet-MG achieves more competitive results on ALD identification.
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Dempsey, Joseph L., Dongfang Wang, Gunseli Siginir, Qiang Fei, Daniel Raftery, Haiwei Gu, and Julia Yue Cui. "Pharmacological Activation of PXR and CAR Downregulates Distinct Bile Acid-Metabolizing Intestinal Bacteria and Alters Bile Acid Homeostasis." Toxicological Sciences 168, no. 1 (November 8, 2018): 40–60. http://dx.doi.org/10.1093/toxsci/kfy271.
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AbstractThe gut microbiome regulates important host metabolic pathways including xenobiotic metabolism and intermediary metabolism, such as the conversion of primary bile acids (BAs) into secondary BAs. The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are well-known regulators for xenobiotic biotransformation in liver. However, little is known regarding the potential effects of PXR and CAR on the composition and function of the gut microbiome. To test our hypothesis that activation of PXR and CAR regulates gut microbiota and secondary BA synthesis, 9-week-old male conventional and germ-free mice were orally gavaged with corn oil, PXR agonist PCN (75 mg/kg), or CAR agonist TCPOBOP (3 mg/kg) once daily for 4 days. PCN and TCPOBOP decreased two taxa in the Bifidobacterium genus, which corresponded with decreased gene abundance of the BA-deconjugating enzyme bile salt hydrolase. In liver and small intestinal content of germ-free mice, there was a TCPOBOP-mediated increase in total, primary, and conjugated BAs corresponding with increased Cyp7a1 mRNA. Bifidobacterium, Dorea, Peptociccaceae, Anaeroplasma, and Ruminococcus positively correlated with T-UDCA in LIC, but negatively correlated with T-CDCA in serum. In conclusion, PXR and CAR activation downregulates BA-metabolizing bacteria in the intestine and modulates BA homeostasis in a gut microbiota-dependent manner.
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Hockertz, S., M. Baccarini, and M. L. Lohmann-Matthes. "Functional heterogeneity of macrophage precursor cells from spleen of Leishmania donovani-infected and untreated mice." Journal of Immunology 142, no. 7 (April 1, 1989): 2489–94. http://dx.doi.org/10.4049/jimmunol.142.7.2489.
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Abstract We recently described the bone marrow-derived macrophage precursor, which is able to spontaneously and extracellularly kill protozoa of the genus Leishmania. These nonadherent, nonphagocytic macrophage precursor cells are present in the spleen of healthy mice only in a small quantity. However, high numbers of proliferating macrophage precursors are isolated from the spleen of Leishmania donovani-infected mice. Macrophage precursors from spleens of diseased animals are able to kill spontaneously the promastigote as well as the amastigote form of L. donovani. The mechanism of the spontaneous leishmanicidal activity of macrophage precursor cells derived from spleens of L. donovani-infected mice was investigated. This effector function could be defined in part as an antibody-dependent cellular cytotoxicity. In addition we assessed the role of CSF-1-containing L cell-conditioned supernatant at the leishmanicidal activity of these immature cells of the macrophage lineage. For that purpose, nonadherent spleen cells from healthy mice were cocultivated with this CSF-1-containing medium for 4 days. These in vitro proliferated macrophage precursor cells from untreated mice showed an increased leishmanicidal activity. Thereby we established a further activation mechanism for proliferating splenic macrophage precursor cells responsible for the observed killing of L. donovani pro- and amastigotes. The spontaneous cytotoxicity of macrophage precursors from spleens of L. donovani-diseased animals is thus defined as a cooperative effect of antibody-dependent cellular cytotoxicity and Macrophage-CSF activation.
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Wang, Yueli, Jing Xi, Peng Wu, Huan Zhang, Xiaoyu Deng, Yong Wang, Zhongchen Ma, Jihai Yi, and Chuangfu Chen. "Small ubiquitin-related modifier 2 affects the intracellular survival of Brucella abortus 2308 by regulating activation of the NF-κB pathway." Innate Immunity 27, no. 1 (November 26, 2020): 81–88. http://dx.doi.org/10.1177/1753425920972171.
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Brucella is a genus of Gram-negative intracellular pathogens that cause animal and human diseases. Brucella survival and replication inside immune cells is critical for the establishment of chronic infections. Protein modifications by small ubiquitin-related modifier proteins and the NF-κB pathway are involved in many cellular activities, playing major roles in regulating protein function that is essential for pathogenic bacteria during infection. However, the relationship between them in the intracellular survival of Brucella is still largely unknown. We demonstrated that Brucella abortus 2308 infection can activate the expression of small ubiquitin-related modifier-2 proteins in a time-dependent manner. We found the production of Th1 cytokines (IFN-γ and TNF-α) and the transcription of NF-κB/p65 were promoted by overexpression and inhibited by interference of small ubiquitin-related modifier-2. In addition, we showed that small ubiquitin-related modifier-2 can inhibit intracellular survival of Brucella abortus 2308 by regulating activation of the NF-κB pathway. Taken together, this work shows that small ubiquitin-related modifier-2 modification of NF-κB2/p65 is essential for the survival of Brucella abortus 2308 inside macrophages. This work may help to unravel the pathogenic mechanisms of Brucella infections.
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Wu, Sichao, Xiaoyu Huang, and Juan Zhang. "Application and Research of the Image Segmentation Algorithm in Remote Sensing Image Buildings." Scientific Programming 2022 (July 1, 2022): 1–9. http://dx.doi.org/10.1155/2022/7927659.
Full textAbstract:
Aiming at the problems of low building segmentation accuracy and blurred edges in high-resolution remote sensing images, an improved fully convolutional neural network is proposed based on the SegNet network. First, GELU, which performs well in deep learning tasks, is selected as the activation function to avoid neuron deactivation. Second, the improved residual bottleneck structure is used in the encoding network to extract more building features. Then, skip connections are used to fuse images The low-level and high-level semantic features are used to assist image reconstruction. Finally, an improved edge correction module is connected at the end of the decoding network to further correct the edge details of the building and improve the edge integrity of the building. Experiments are carried out on the Massachusetts building dataset, and the precision rate, recall rate, and F1 value reach 93.5%, 79.3%, and 81.9%, respectively, and the comprehensive evaluation index F1 value is improved by about 5% compared with the basic network.
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Yang, Xiliang, Jianglian She, Jinping Liu, Tao Yang, Gege An, Qingru Chen, Cheng Fan, et al. "A Comprehensive Review of the Genus Pyrola Herbs in Traditional Uses, Phytochemistry and Pharmacological Activities." Current Topics in Medicinal Chemistry 20, no. 1 (January 22, 2020): 57–77. http://dx.doi.org/10.2174/1568026619666191203112412.
Full textAbstract:
Pyrola (Pyrolaceae), also known as Luxiancao/鹿衔草in China, was recorded in Sheng Nong’s Herbal Classic listed in top grade. Pyrola herbs were used as medicinal plants for a long history with wide-ranging activities such as nourishing kidney-yang, strengthening muscles and bones, activating blood, stopping bleeding, dispelling rheumatism, and eliminating dampness. Currently, the research on Pyrola plants is increasing year by year but there is no comprehensive and detailed review concerning genus Pyrola. This review aims to sum up the updated and comprehensive information about botany and traditional use, phytochemistry, pharmacological activities and safety by analyzing the information available on Pyrola plants via internationally accepted scientific databases. Collectively, more than 100 compounds have been isolated from the Pyrola plants. Furthermore, a total of 33 prescriptions containing Pyrola plants are compiled in this review. Pyrola plants are used as indispensable agents in traditional Chinese medicine due to its activities of antimicrobial, anti-inflammatory, antioxidant, lipidlowering, cardiovascular and cerebrovascular protection, proliferation of osteoblasts promoting, antineoplastic and etc. Further work should be developed on the elucidation of structure-function relationship, understanding of multi-target pharmacological effects, as well as developing its application both in clinical usage and functional food for research and development of Pyrola plants.
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Huang, Xiao-Fan, Kai-Fu Chang, Shan-Chih Lee, Chia-Yu Li, Hung-Hsiu Liao, Ming-Chang Hsieh, and Nu-Man Tsai. "Extract of Juniperus indica Bertol Synergizes with Cisplatin to Inhibit Oral Cancer Cell Growth via Repression of Cell Cycle Progression and Activation of the Caspase Cascade." Molecules 25, no. 12 (June 13, 2020): 2746. http://dx.doi.org/10.3390/molecules25122746.
Full textAbstract:
Oral cancer—a type of head and neck cancer—is estimated to be the fifth most common cancer in Taiwan. However, efficacious therapies for oral cancer are still lacking due to drug resistance and recurrence. Consequently, the identification of new anticancer agents for clinical treatment is needed. Juniperus indica Bertol is a plant of the Juniperus genus often used as a treatment in traditional medicine due to its anti-inflammatory, antibacterial and diuretic functions. The biofunctions of Juniperus indica Bertol including its anticancer potential, have not been fully explored. As a result, the aim of this research was to investigate the anticancer activity of Juniperus indica Bertol extract (JIB extract) and determine whether JIB extract has synergistic effects with cisplatin in oral cancer. These results are the first to demonstrate that JIB extract exhibits anticancer capacity and synergizes with cisplatin to treat oral cancer. Our findings indicate that JIB extract has a potential to develop anticancer agent and chemo therapeutic adjuvant for oral cancer.
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Tobias, Nicholas J., Tilman Ahrendt, Ursula Schell, Melissa Miltenberger, Hubert Hilbi, and Helge B. Bode. "Legionellashows a diverse secondary metabolism dependent on a broad spectrum Sfp-type phosphopantetheinyl transferase." PeerJ 4 (November 24, 2016): e2720. http://dx.doi.org/10.7717/peerj.2720.
Full textAbstract:
Several members of the genusLegionellacause Legionnaires’ disease, a potentially debilitating form of pneumonia. Studies frequently focus on the abundant number of virulence factors present in this genus. However, what is often overlooked is the role of secondary metabolites fromLegionella. Following whole genome sequencing, we assembled and annotated theLegionella parisiensisDSM 19216 genome. Together with 14 other members of theLegionella, we performed comparative genomics and analysed the secondary metabolite potential of each strain. We found thatLegionellacontains a huge variety of biosynthetic gene clusters (BGCs) that are potentially making a significant number of novel natural products with undefined function. Surprisingly, only a single Sfp-like phosphopantetheinyl transferase is found in allLegionellastrains analyzed that might be responsible for the activation of all carrier proteins in primary (fatty acid biosynthesis) and secondary metabolism (polyketide and non-ribosomal peptide synthesis). Using conserved active site motifs, we predict some novel compounds that are probably involved in cell-cell communication, differing to known communication systems. We identify several gene clusters, which may represent novel signaling mechanisms and demonstrate the natural product potential ofLegionella.
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Koumoutsi, Alexandra, Xiao-Hua Chen, Joachim Vater, and Rainer Borriss. "DegU and YczE Positively Regulate the Synthesis of Bacillomycin D by Bacillus amyloliquefaciens Strain FZB42." Applied and Environmental Microbiology 73, no. 21 (September 7, 2007): 6953–64. http://dx.doi.org/10.1128/aem.00565-07.
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ABSTRACT Environmental strain Bacillus amyloliquefaciens FZB42 differs from the domesticated model organism of the same genus, Bacillus subtilis 168, in its ability to promote plant growth and suppress plant-pathogenic organisms present in the rhizosphere. This behavior is exerted mainly through the production of several nonribosomal cyclic lipopeptides and polyketides, which exhibit a broad range of action against phytopathogenic bacteria, fungi, and nematodes. Here, we provide evidence that the synthesis of the main antifungal agent of B. amyloliquefaciens FZB42, bacillomycin D, is regulated in multiple layers. Expression of the bacillomycin D operon (bmy) is dependent on a single σA-dependent promoter, Pbmy and is favored in its natural host by the small regulatory protein DegQ. The global regulators DegU and ComA are required for the full transcriptional activation of bmy. DegU retains a key role since it binds directly to two sites located upstream of the bacillomycin D promoter. Moreover, both DegU and a transmembrane protein of unknown function, YczE, act on a later level of gene expression, exerting their posttranscriptional effects in a hitherto-unknown manner.