76 research outputs found

    Conservation and implications of eukaryote transcriptional regulatory regions across multiple species

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    <p>Abstract</p> <p>Background</p> <p>Increasing evidence shows that whole genomes of eukaryotes are almost entirely transcribed into both protein coding genes and an enormous number of non-protein-coding RNAs (ncRNAs). Therefore, revealing the underlying regulatory mechanisms of transcripts becomes imperative. However, for a complete understanding of transcriptional regulatory mechanisms, we need to identify the regions in which they are found. We will call these transcriptional regulation regions, or TRRs, which can be considered functional regions containing a cluster of regulatory elements that cooperatively recruit transcriptional factors for binding and then regulating the expression of transcripts.</p> <p>Results</p> <p>We constructed a hierarchical stochastic language (HSL) model for the identification of core TRRs in yeast based on regulatory cooperation among TRR elements. The HSL model trained based on yeast achieved comparable accuracy in predicting TRRs in other species, e.g., fruit fly, human, and rice, thus demonstrating the conservation of TRRs across species. The HSL model was also used to identify the TRRs of genes, such as p53 or <it>OsALYL1</it>, as well as microRNAs. In addition, the ENCODE regions were examined by HSL, and TRRs were found to pervasively locate in the genomes.</p> <p>Conclusion</p> <p>Our findings indicate that 1) the HSL model can be used to accurately predict core TRRs of transcripts across species and 2) identified core TRRs by HSL are proper candidates for the further scrutiny of specific regulatory elements and mechanisms. Meanwhile, the regulatory activity taking place in the abundant numbers of ncRNAs might account for the ubiquitous presence of TRRs across the genome. In addition, we also found that the TRRs of protein coding genes and ncRNAs are similar in structure, with the latter being more conserved than the former.</p

    Long Non-coding RNA CASC2 Enhances the Antitumor Activity of Cisplatin Through Suppressing the Akt Pathway by Inhibition of miR-181a in Esophageal Squamous Cell Carcinoma Cells

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    Background: Long non-coding RNA CASC2 (lncRNA CASC2) has been found to be down-regulated in esophageal squamous cell carcinoma (ESCC). However, the effect of CASC2 on cisplatin-treated ESCC was unclear. The present study aimed to evaluate the role of CASC2 in cisplatin-treated ESCC cells.Methods: The expression levels of CASC2 and miR-181a were detected by qRT-PCR. Cell viability was measured by MTT assay. The cytotoxicity effect was detected by lactate dehydrogenase (LDH) release assay. Cell apoptosis was tested by flow cytometry. The protein levels of protein kinase B (Akt) and p-Akt were detected by western blotting.Results: The results showed that CASC2 was low-expressed in ESCC cell lines. Overexpression of CASC2 enhanced the inhibitory effect of cisplatin on cell viability and promoted cisplatin-induced LDH release and apoptosis. We also found that miR-181a expression levels were increased in ESCC cell lines. MiR-181a inhibitor enhanced the antitumor activity of cisplatin, which was similar with the effect of CASC2. CASC2 directly interacted with miR-181a and inhibited the miR-181a expression. MiR-181a reversed the effects of CASC2 on antitumor activity of cisplatin. In addition, we also found that CASC2 suppressed the Akt pathway by inhibiting miR-181a.Conclusions: CASC2 promoted the antitumor activity of cisplatin through inhibiting Akt pathway via negatively regulating miR-181a in ESCC cells. The results provide a new insight for ESCC therapy

    Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast Cancer

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    The off-target activation of photosensitizers is one of the most well-known obstacles to effective photodynamic therapy (PDT). The selected activation of photosensitizers in cancer cells is highly desired to overcome this problem. We developed a strategy that enabled diselenide bonds to link hyaluronic acid (HA) and photosensitizer chlorin e6 (Ce6) to assemble the micelles (HA-sese-Ce6 NPs) that can target cancer and achieve a redox responsive release of drugs to enhance the PDT efficiency in breast cancer. The HA was used to form a hydrophilic shell that can target cluster of differentiation 44 (CD44) on the cancer cells. The selenium-containing core is easily dissembled in a redox environment to release Ce6. The triggered release of Ce6 in a redox condition and the positive feedback release by activated Ce6 were observed in vitro. In cytotoxicity assays and in vitro cellular uptake assays, the increased PDT efficiency and targeted internalization of HA-sese-Ce6 NPs in the cells were verified, compared to a free Ce6 treated group. Similar results were showed in the therapeutic study and in vivo fluorescence imaging in an orthotopic mammary fat pad tumor model. In addition, a significant inhibition of metastasis was found after the HA-sese-Ce6 NPs treatment. In general, this study promises an ingenious and easy strategy for improved PDT efficiency

    A Determination Method of Optimal Customization Degree of Logistics Service Supply Chain with Mass Customization Service

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    Customization degree is a very important field of mass customization. Its improvement could enhance customer satisfaction and further increase customer demand while correspondingly it will increase service price and decrease customer satisfaction and demand. Therefore this paper discusses how to deal with such issues in logistics service supply chain (LSSC) with a logistics service integrator (LSI) and a customer. With the establishment of customer demand function for logistics services and profit functions of the LSI and the customer, three different decision modes are proposed (i.e., customization degree dominated by LSI, customization degree dominated by customer, and customization degree decided by concentrated supply chain); many interesting findings are achieved. Firstly, to achieve customization cooperation between LSI and customer, measures should be taken to make the unit increase cost of the customized logistics services lower than a certain value. Secondly, there are differences between the optimal customization degree dominated by LSI and that dominated by customer. And in both cases, the dominator could realize more profit than the follower. Thirdly, with the profit secondary distribution strategy, the modified decentralized decision mode could accomplish the maximum profit achieved in centralized decision mode and meanwhile get the optimal customization degree

    Innovative Mechanisms for Precision Assembly and Actuation of Arrays of Nanowire Oscillators

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    Bottom-up assembling of Micro/Nano Electromechanical System (MEMS/NEMS) devices from nanoscale building blocks is highly desirable but extremely difficult to achieve. In this work, we report innovative mechanisms for precision assembly and actuation of arrays of nanowire NEMS devices that can synchronously oscillate between two designated positions for over 4000 cycles. The assembly and actuation mechanisms are based on unique magnetic interactions between nanoentities with perpendicular magnetic anisotropy (PMA) and electric-tweezer manipulation, our recent invention. Quantitative analysis of the dynamics of torques involved in the nano-oscillators reveals that the induced electrostatic torques due to the external electric fields between metallic NEMS components play a significant role in the mechanical actuation. These new findings are expected to inspire new in situ assembly and actuation strategies in the general field of NEMS devices such as nanomechanical switches for toggling on/off circuits and nanoresonators for biochemical sensors and radio frequency communication

    Innovative Mechanisms for Precision Assembly and Actuation of Arrays of Nanowire Oscillators

    No full text
    Bottom-up assembling of Micro/Nano Electromechanical System (MEMS/NEMS) devices from nanoscale building blocks is highly desirable but extremely difficult to achieve. In this work, we report innovative mechanisms for precision assembly and actuation of arrays of nanowire NEMS devices that can synchronously oscillate between two designated positions for over 4000 cycles. The assembly and actuation mechanisms are based on unique magnetic interactions between nanoentities with perpendicular magnetic anisotropy (PMA) and electric-tweezer manipulation, our recent invention. Quantitative analysis of the dynamics of torques involved in the nano-oscillators reveals that the induced electrostatic torques due to the external electric fields between metallic NEMS components play a significant role in the mechanical actuation. These new findings are expected to inspire new in situ assembly and actuation strategies in the general field of NEMS devices such as nanomechanical switches for toggling on/off circuits and nanoresonators for biochemical sensors and radio frequency communication

    Innovative Mechanisms for Precision Assembly and Actuation of Arrays of Nanowire Oscillators

    No full text
    Bottom-up assembling of Micro/Nano Electromechanical System (MEMS/NEMS) devices from nanoscale building blocks is highly desirable but extremely difficult to achieve. In this work, we report innovative mechanisms for precision assembly and actuation of arrays of nanowire NEMS devices that can synchronously oscillate between two designated positions for over 4000 cycles. The assembly and actuation mechanisms are based on unique magnetic interactions between nanoentities with perpendicular magnetic anisotropy (PMA) and electric-tweezer manipulation, our recent invention. Quantitative analysis of the dynamics of torques involved in the nano-oscillators reveals that the induced electrostatic torques due to the external electric fields between metallic NEMS components play a significant role in the mechanical actuation. These new findings are expected to inspire new in situ assembly and actuation strategies in the general field of NEMS devices such as nanomechanical switches for toggling on/off circuits and nanoresonators for biochemical sensors and radio frequency communication

    Innovative Mechanisms for Precision Assembly and Actuation of Arrays of Nanowire Oscillators

    No full text
    Bottom-up assembling of Micro/Nano Electromechanical System (MEMS/NEMS) devices from nanoscale building blocks is highly desirable but extremely difficult to achieve. In this work, we report innovative mechanisms for precision assembly and actuation of arrays of nanowire NEMS devices that can synchronously oscillate between two designated positions for over 4000 cycles. The assembly and actuation mechanisms are based on unique magnetic interactions between nanoentities with perpendicular magnetic anisotropy (PMA) and electric-tweezer manipulation, our recent invention. Quantitative analysis of the dynamics of torques involved in the nano-oscillators reveals that the induced electrostatic torques due to the external electric fields between metallic NEMS components play a significant role in the mechanical actuation. These new findings are expected to inspire new in situ assembly and actuation strategies in the general field of NEMS devices such as nanomechanical switches for toggling on/off circuits and nanoresonators for biochemical sensors and radio frequency communication
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