Regulation of chromatin positioning in Arabidopsis thaliana

The biochemical environment within the 3D nuclear space is not homogeneous. It has been demonstrated in many studies that the transcriptional activity of a gene is linked to its positioning inside the nuclear space. The NE not only serves as a physical barrier separating the nuclear content from the cytoplasm but also plays crucial roles in mediating the 3D organization of genomic DNA. Following the discovery of LADs, which are transcriptionally repressed chromatin regions, the non-random chromatin positioning at the NP and its biological relevance have been studied intensively in animals. However, it still remains unknown in plants that whether comparable chromatin organizations exist or not. In this study, RE-ChIP was used to reveal the genome-wide identification of non-random organization of chromatin domains positioned at the peripheral zone of Arabidopsis thaliana nuclei. The patterns of chromatin regions positioned at NP were similar across different tissues. These chromatin domains are enriched with silenced protein-coding genes, TE genes and heterochromatic marks, which collectively define a repressed environment at the NP. Furthermore, our results suggest a spatial compartment of different DNA methylation pathways that regulate TE silencing, where the CHH DNA methylation of TEs localized at the NP and in the nuclear interior is preferentially mediated by CMT2 and DRM methyltransferases, respectively. To elucidate how such chromatin positioning patterns at the NP was achieved in plants, dual-color FISH experiments were conducted to compare the difference of chromatin-NP interactions among various mutants. Our results show that in Arabidopsis thaliana, specific chromatin positioning at the NP requires plant lamin proteins CRWN1, CRWN4 and non-CG DNA methylation, which are all plant-specific. The result of chromosome painting indicates global attenuation of chromatin positioning patterns at the NP in both the crwn1 and crwn4 mutants. Moreover, ChIP-seq shows that CRWN1 directly interacts with chromatin regions localized at the NP. In summary, the NP is a functional sub-compartment enriched with heterochromatic domains. In addition, CRWN1 is a key component of lamin-chromatin network in plants. It is functionally equivalent to animals lamins, which play crucial roles in regulating chromatin positioning at the NP

GreatSplicing: A Semantically Rich Splicing Dataset

In existing splicing forgery datasets, the insufficient semantic varieties of spliced regions cause a problem that trained detection models overfit semantic features rather than splicing traces. Meanwhile, because of the absence of a reasonable dataset, different detection methods proposed cannot reach a consensus on experimental settings. To address these urgent issues, GreatSplicing, a manually created splicing dataset with a considerable amount and high quality, is proposed in this paper. GreatSplicing comprises 5,000 spliced images and covers spliced regions with 335 distinct semantic categories, allowing neural networks to grasp splicing traces better. Extensive experiments demonstrate that models trained on GreatSplicing exhibit minimal misidentification rates and superior cross-dataset detection capabilities compared to existing datasets. Furthermore, GreatSplicing is available for all research purposes and can be downloaded from www.greatsplicing.net

GSK3β Is Involved in JNK2-Mediated β-Catenin Inhibition

We have recently reported that mitogen-activated protein kinase (MAPK) JNK1 downregulates beta-catenin signaling and plays a critical role in regulating intestinal homeostasis and in suppressing tumor formation. This study was designed to determine whether JNK2, another MAPK, has similar and/or different functions in the regulation of beta-catenin signaling.We used an in vitro system with manipulation of JNK2 and beta-catenin expression and found that activated JNK2 increased GSK3beta activity and inhibited beta-catenin expression and transcriptional activity. However, JNK2-mediated downregulation of beta-catenin was blocked by the proteasome inhibitor MG132 and GSK3beta inhibitor lithium chloride. Moreover, targeted mutations at GSK3beta phosphorylation sites (Ser33 and Ser37) of beta-catenin abrogated JNK2-mediated suppression of beta-catenin. In vivo studies further revealed that JNK2 deficiency led to upregulation of beta-catenin and increase of GSK3-beta phosphorylation in JNK2-/- mouse intestinal epithelial cells. Additionally, physical interaction and co-localization among JNK2, beta-catenin and GSK3beta were observed by immunoprecipitation, mammalian two-hybridization assay and confocal microscopy, respectively.In general, our data suggested that JNK2, like JNK1, interacts with and suppresses beta-catenin signaling in vitro and in vivo, in which GSK3beta plays a key role, although previous studies have shown distinct functions of JNK1 and JNK2. Our study also provides a novel insight into the crosstalk between Wnt/beta-catenin and MAPK JNKs signaling

Flavonoids and its derivatives from Callistephus chinensis flowers and their inhibitory activities against alpha-glucosidase

Inhibitors of carbohydrate-hydrolysing enzymes play an important role for the treatment of diabetes. One of the therapeutic methods for decreasing of postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate-hydrolysing enzymes, such as α-glucosidase, in the digestive organs. To investigate the therapeutic potential of compounds from natural sources, Callistephus chinensis flowers (CCF) were tested for inhibition of α-glucosidase, and acarboes was used as the positive control. The 70 % ethanol extract of CCF exhibited significant α-glucosidase inhibitory activities with IC50 value of 8.14 μg/ml. The stepwise polarity fractions of CCF were tested further for in vitro inhibition of α-glucosidase. The ethyl acetate (EtOAc) fraction exhibited the most significant inhibitory activity. Eight pure compounds, apigenin, apigenin-7-O-β-D-glucoside, kaempferol, hyperin, naringenin, quercetin, luteolin, and kaempferol-7-O-β-D-glucoside, were isolated (using enzyme assay-guide fractionation method) from the EtOAc fraction. Among these, quercetin was the most active one (IC50 values 2.04 μg/ml), and it appears that the inhibiting percentages are close to acarbose (IC50 values 2.24 μg/ml), the positive control, on α-glucosidase inhibition. HPLC/UV analysis indicated that the major components of CCF are kaempferol, hyperin and quercetin. The presented results revealed that CCF containing these eight flavonoids could be a useful natural source in the development of a novel α-glucosidase inhibitory agent against diabetic complications

Transcriptional Regulation and Biological Functions of Selenium-Binding Protein 1 in Colorectal Cancer In Vitro and in Nude Mouse Xenografts

It has been shown that selenium-binding protein 1 (SBP1) is significantly downregulated in different human cancers. Its regulation and function have not yet been established.We show that the SBP1 promoter is hypermethylated in colon cancer tissues and human colon cancer cells. Treatment with 5'-Aza-2'-deoxycytidine leads to demethylation of the SBP1 promoter and to an increase of SBP1 promoter activity, rescues SBP1 mRNA and protein expression in human colon cancer cells. Additionally, overexpression of SBP1 sensitizes colon cancer cells to H2O2-induced apoptosis, inhibits cancer cell migration in vitro and inhibits tumor growth in nude mice.These data demonstrate that SBP1 has tumor suppressor functions that are inhibited in colorectal cancer through epigenetic silencing

Detecting Generated Images by Real Images Only

As deep learning technology continues to evolve, the images yielded by generative models are becoming more and more realistic, triggering people to question the authenticity of images. Existing generated image detection methods detect visual artifacts in generated images or learn discriminative features from both real and generated images by massive training. This learning paradigm will result in efficiency and generalization issues, making detection methods always lag behind generation methods. This paper approaches the generated image detection problem from a new perspective: Start from real images. By finding the commonality of real images and mapping them to a dense subspace in feature space, the goal is that generated images, regardless of their generative model, are then projected outside the subspace. As a result, images from different generative models can be detected, solving some long-existing problems in the field. Experimental results show that although our method was trained only by real images and uses 99.9\% less training data than other deep learning-based methods, it can compete with state-of-the-art methods and shows excellent performance in detecting emerging generative models with high inference efficiency. Moreover, the proposed method shows robustness against various post-processing. These advantages allow the method to be used in real-world scenarios

D-Unet: A Dual-encoder U-Net for Image Splicing Forgery Detection and Localization

Recently, many detection methods based on convolutional neural networks (CNNs) have been proposed for image splicing forgery detection. Most of these detection methods focus on the local patches or local objects. In fact, image splicing forgery detection is a global binary classification task that distinguishes the tampered and non-tampered regions by image fingerprints. However, some specific image contents are hardly retained by CNN-based detection networks, but if included, would improve the detection accuracy of the networks. To resolve these issues, we propose a novel network called dual-encoder U-Net (D-Unet) for image splicing forgery detection, which employs an unfixed encoder and a fixed encoder. The unfixed encoder autonomously learns the image fingerprints that differentiate between the tampered and non-tampered regions, whereas the fixed encoder intentionally provides the direction information that assists the learning and detection of the network. This dual-encoder is followed by a spatial pyramid global-feature extraction module that expands the global insight of D-Unet for classifying the tampered and non-tampered regions more accurately. In an experimental comparison study of D-Unet and state-of-the-art methods, D-Unet outperformed the other methods in image-level and pixel-level detection, without requiring pre-training or training on a large number of forgery images. Moreover, it was stably robust to different attacks.Comment: 13 pages, 13 figure

Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice.

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin in human colorectal cancer cells, we found that E-cadherin, a protein that regulates cell-cell adhesion, epithelial-mesenchymal transition and metastasis, was almost completely lost in Dcn(-/-) mouse intestine, and loss of decorin and E-cadherin accelerated colon cancer cell growth and invasion in Dcn(-/-) mice. However, increasing decorin expression in colorectal cancer cells attenuated cancer cell malignancy, including inhibition of cancer cell proliferation, promotion of apoptosis and importantly, attenuation of cancer cell migration. All these changes were linked to the regulation of E-cadherin by decorin. Moreover, overexpression of decorin upregulated E-cadherin through increasing of E-cadherin protein stability as E-cadherin messenger RNA and promoter activity were not affected. Co-immunoprecipitation assay showed a physical binding between decorin and E-cadherin proteins. Taken together, our results provide direct evidence that decorin-mediated inhibition of colorectal cancer growth and migration are through the interaction with and stabilization of E-cadherin

Precision delivery of RAS-inhibiting siRNA to KRAS driven cancer via peptide-based nanoparticles

Over 95% of pancreatic adenocarcinomas (PDACs), as well as a large fraction of other tumor types, such as colorectal adenocarcinoma, are driven by KRAS activation. However, no direct RAS inhibitors exist for cancer therapy. Furthermore, the delivery of therapeutic agents of any kind to PDAC in particular has been hindered by the extensive desmoplasia and resultant drug delivery challenges that accompanies these tumors. Small interfering RNA (siRNA) is a promising modality for anti-neoplastic therapy due to its precision and wide range of potential therapeutic targets. Unfortunately, siRNA therapy is limited by low serum half-life, vulnerability to intracellular digestion, and transient therapeutic effect. We assessed the ability of a peptide based, oligonucleotide condensing, endosomolytic nanoparticle (NP) system to deliver siRNA to KRAS-driven cancers. We show that this peptide-based NP is avidly taken up by cancer cell