A Novel Dataset and a Deep Learning Method for Mitosis Nuclei Segmentation and Classification

Mitosis nuclei count is one of the important indicators for the pathological diagnosis of breast cancer. The manual annotation needs experienced pathologists, which is very time-consuming and inefficient. With the development of deep learning methods, some models with good performance have emerged, but the generalization ability should be further strengthened. In this paper, we propose a two-stage mitosis segmentation and classification method, named SCMitosis. Firstly, the segmentation performance with a high recall rate is achieved by the proposed depthwise separable convolution residual block and channel-spatial attention gate. Then, a classification network is cascaded to further improve the detection performance of mitosis nuclei. The proposed model is verified on the ICPR 2012 dataset, and the highest F-score value of 0.8687 is obtained compared with the current state-of-the-art algorithms. In addition, the model also achieves good performance on GZMH dataset, which is prepared by our group and will be firstly released with the publication of this paper. The code will be available at: https://github.com/antifen/mitosis-nuclei-segmentation.Comment: 19 pages,11 figures, 4 table

Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Activator protein 2 gamma (AP-2γ) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2γ has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis.</p> <p>Methods</p> <p>To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2γ binding sites on genomic DNA from human breast cancer cell line MDA-MB-453.</p> <p>Results</p> <p>20 novel DNA fragments proximal to potential AP-2γ targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2γ target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2γ. Decreased expression and overexpression of AP-2γ in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2γ directly regulates them.</p> <p>Conclusion</p> <p>This suggested that AP-2γ can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future.</p

Modulation of B cell activation threshold mediated by BCR/CD40 costimulation by targeting Cbl-b for ubiquitination

It has been shown that CD40 is required for optimal B cell activation. Casitas-B-lineage lymphoma-b (Cbl-b), a RING finger E3 ubiquitin ligase, inhibits B cell activation. In this report, we demonstrate that CD40 stimulation markedly enhances IgM-induced B cell proliferation in wild-type (WT) mice, whereas this cell proliferation was reduced in CD40-deficient (Cd40−/−) mice. Interestingly, CD40 ligation strongly augments IgM-induced Cbl-b ubiquitination and degradation in primary mouse B cells, which closely correlates with their proliferation capacity. Cbl-b deficiency uncouples BCR-induced B cell proliferation from CD40 costimulation. Our results indicate that Cbl-b negatively regulates costimulation of BCR and CD40, possibly by setting the threshold for B cell activation via controlling Cbl-b expression

FDMLNet: A Frequency-Division and Multiscale Learning Network for Enhancing Low-Light Image

Low-illumination images exhibit low brightness, blurry details, and color casts, which present us an unnatural visual experience and further have a negative effect on other visual applications. Data-driven approaches show tremendous potential for lighting up the image brightness while preserving its visual naturalness. However, these methods introduce hand-crafted holes and noise enlargement or over/under enhancement and color deviation. For mitigating these challenging issues, this paper presents a frequency division and multiscale learning network named FDMLNet, including two subnets, DetNet and StruNet. This design first applies the guided filter to separate the high and low frequencies of authentic images, then DetNet and StruNet are, respectively, developed to process them, to fully explore their information at different frequencies. In StruNet, a feasible feature extraction module (FFEM), grouped by multiscale learning block (MSL) and a dual-branch channel attention mechanism (DCAM), is injected to promote its multiscale representation ability. In addition, three FFEMs are connected in a new dense connectivity meant to utilize multilevel features. Extensive quantitative and qualitative experiments on public benchmarks demonstrate that our FDMLNet outperforms state-of-the-art approaches benefiting from its stronger multiscale feature expression and extraction ability

El laboratorio de hidráulica "Jorge Ramírez Giraldo" en sus 30 años

El Laboratorio de Hidráulica de la Universidad Nacional de Colombia Sede Manizales nació en 1987 al calor de los estudios en modelos hidráulicos que requería el proyecto Miel I. El espacio que ocupa detrás del Museo SAMOGA -Campus Palogrande-, era entonces, un área con viejos árboles de eucalipto y una cancha de tejo que se despejó para construir los modelos de Miel I. Una vez construidos estos, y durante su estudio -año 1987 a 1989- se definió la nueva infraestructura académica de la Universidad, que ocupaba 2.000 m2 con laboratorio, oficina y zona verde, rodeada por un cerramient

Hybrid membrane camouflaged Prussian blue nanoparticles with cinobufagin loading for chemo/photothermal therapy of colorectal cancer

The natural compound of cinobufagin (CS-1) has showed potential application for colorectal cancer therapy. However, the limitation of hydrophobicity and cardiotoxicity appealed for the improvement of compound formulation. Meanwhile, sole chemotherapy for colorectal cancer (CRC) is facing the challenges of finite accumulation of drugs in tumor sites and nonspecific toxicity. In order to overcome these limitations, cinobufagin loaded in Prussian Blue nanoparticles (PC NPs) were prepared for CRC therapy by combining with photothermal therapy (PTT). The hybrid cell membranes coating was adopted to endow immune escape and tumor homing capacity of PC@M NPs. Both in vitro and in vivo assay demonstrated that the chemo/photothermal therapy not only suppressed CRC growth, but also inhibited the metastasis of primary by downregulating the expression of Vimentin, matrix metalloproteinase-9 (MMP-9) and hypoxia-inducible factor1-alpha (HIF-1α). Moreover, this strategy modulated the intestinal microbiota of CRC-bearing mice to a normal level in some extent. Taken together, this proposed nanoplatform presents a potential strategy for CRC therapy

Bone Marrow Mesenchymal Stromal Cell-Derived Periostin Promotes B-ALL Progression by Modulating CCL2 in Leukemia Cells

Summary: Periostin (POSTN) is a multifunctional extracellular component that regulates cell-matrix interactions and cell-cell crosstalk. POSTN deletion significantly decreases leukemia burden in mice; however, the underlying mechanisms by which POSTN promotes B cell acute lymphoblastic leukemia (B-ALL) progression remain largely unknown. Here, we demonstrate that bone marrow (BM)-derived mesenchymal stromal cells (BM-MSCs) express higher levels of POSTN when co-cultured with B-ALL cells in vitro and in vivo. POSTN deficiency in BM-MSCs significantly decreases CCL2 expression in co-cultured B-ALL cells in vitro and in vivo. Moreover, POSTN treatment increases expression of CCL2 in B-ALL cells by activating the integrin-ILK-NF-κB pathway. Conversely, CCL2 treatment upregulates expression of POSTN in BM-MSCs via STAT3 activation. Furthermore, there is a positive correlation between POSTN expression and CCL2 level in the BM of mice and patients with B-ALL. These findings suggest that B-ALL cell-derived CCL2 contributes to the increased leukemia burden promoted by BM-MSC-derived POSTN. : Ma et al. show that BM-MSC-derived periostin promotes leukemia progression by activating the integrin-ILK-NF-κB-CCL2 pathway in leukemia cells and that leukemia cell-derived CCL2 increases periostin expression in BM-MSCs by activating STAT3. This work identifies critical crosstalk between leukemia cells and stromal cells via periostin and CCL2 in B-ALL progression. Keywords: periostin, CCL2, MSC, B-ALL, leukemia, bone marrow, extracellular matrix, matricellular protei

Characterization of genotype IV hepatitis E virus-like particles expressed in E.coli

HEV (Hepatitis E virus) is an infectious disease transmitted between humans and animals, which poses a severe threat to the biological safety and property throughout the world. The disease is especially severe in patients with potential liver cirrhosis and women during pregnancy. There is no specific and thorough HEV treatment at present. The development of hepatitis E virus vaccine is vital to the prevention of viral hepatitis worldwide. Since HEV cannot grow adequately in vitro, vaccine developed by devitalized virus particles does not work. Exploration of HEV-like structures is essential for the development of functional vaccines against HEV infection. ORF2 encodes the structural proteins of HEV, some of which can automatically assemble into virus-like particles (VLP) in this experiment, the recombinant capsid protein p27 was expressed in E. coli and the VLP formed by p27 was used to immunize mice. The results showed that the VLP formed by recombinant P27 had similar particle size to that of HEV; the immune dose produced by p27 was positively correlated with the immune effect. Compared with other genetic engineering subunit vaccines, P27 protein has a better application prospect