Identification and characterization of novel components in brassinosteroid signaling and biosynthetic pathways in Arabidopsis thaliana

Brassinosteroids (BRs) are steroidal hormones essential for normal plant growth and development. To dissect the essential role of BRs in plants, a gain-of-function approach, activation tagging, was used to identify components functioning in BR signaling and biosynthetic pathways in the model plant, Arabidopsis thaliana. In the dissertation research, two molecules were identified and characterized to be the novel regulators of the BR pathways. TCP1 was identified as a suppressor of a weak allele of BR receptor mutant. And TCP1 was identified as the first positive regulator of BR biosynthesis by regulating the expression of DWF4, a rate-limiting BR biosynthetic enzyme. CUR was identified as an enhancer of the weak allele of BR receptor mutant. CUR regulates leaf morphogenesis by controlling the expression of homeotic genes. CUR may connect the leaf development with BR signaling pathway in plant growth and development

An Ethereum-compatible blockchain that explicates and ensures design-level safety properties for smart contracts

Smart contracts are crucial elements of decentralized technologies, but they face significant obstacles to trustworthiness due to security bugs and trapdoors. To address the core issue, we propose a technology that enables programmers to focus on design-level properties rather than specific low-level attack patterns. Our proposed technology, called Theorem-Carrying-Transaction (TCT), combines the benefits of runtime checking and symbolic proof. Under the TCT protocol, every transaction must carry a theorem that proves its adherence to the safety properties in the invoked contracts, and the blockchain checks the proof before executing the transaction. The unique design of TCT ensures that the theorems are provable and checkable in an efficient manner. We believe that TCT holds a great promise for enabling provably secure smart contracts in the future. As such, we call for collaboration toward this vision

Evaluation of Anti-tumor and Chemoresistance-lowering Effects of Pectolinarigenin from Cirsium japonicum Fisch ex DC in Breast Cancer

Purpose: To investigate the antitumor and chemoresistance-lowering effects of pectolinarigenin on breast cancer cells.Methods: Pectolinarigenin was purified by a combination of silica gel and Sephadex LH-20 column chromatography from ethanol extracts of the aerial parts of C. japonicum DC. Breast cancer selfrenewal properties were tested by colony formation and tumor sphere formation assays. Thereafter, real-time polymerase chain reaction (PCR) was used to detect breast cancer stem cell markers. Furthermore, the effect of pectolinarigenin on breast cancer cell was evaluated by chemoresistance using 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Finally, tumor formation in nude mice was used to test the effect of pectolinarigenin on tumorigenicity of breast cancer cells in vivo.Results: The results showed that pectolinarigenin, extracted from Cirsium japonicum Fisch. ex DC., inhibited tumor cell self-renewal in MCF-7 breast cancer cells. Pectolinarigenin (25 μM) caused significant inhibition of colony formation (61.23 %, p < 0.001) and tumor sphere formation (59.49 %, p < 0.01) in MCF-7. The inhibitory effects were associated with changes in breast cancer stem cell markers. Treatment of breast cancer cells with pectolinarigenin reduced the chemoresistance of the cells to doxorubicin. At the same time, mRNA expression of chemoresistance genes (ATP binding cassette subfamily G member 2, ABCG2 and ATP binding cassette subfamily B member 1, MDR1) was repressed by pectolinarigenin. The inhibition efficiency of MDR1 and ABCG2 by 10 μM pectolinarigenin treatment was about 59.29 (p < 0.01) and 46.48 % (p < 0.01), respectively. Furthermore, pectolinarigenin reduced tumor mass in nude mice xenograft model.Conclusion: Pectolinarigenin inhibits breast cancer stem cell-like properties and lowers the chemoresistance of the cancer cells to chemotherapy. The results provide an insight into the mechanism of the anti-breast tumor effects and an experimental basis for the use of pectolinarigenin to enhance treatment of patients with breast cancer.Keywords: Pectolinarigenin, Cancer stem cells, Breast cancer, Chemoresistance, Cirsium japonicum Fisch. ex D

RDAD: A Machine Learning System to Support Phenotype-Based Rare Disease Diagnosis

DNA sequencing has allowed for the discovery of the genetic cause for a considerable number of diseases, paving the way for new disease diagnostics. However, due to the lack of clinical samples and records, the molecular cause for rare diseases is always hard to identify, significantly limiting the number of rare Mendelian diseases diagnosed through sequencing technologies. Clinical phenotype information therefore becomes a major resource to diagnose rare diseases. In this article, we adopted both a phenotypic similarity method and a machine learning method to build four diagnostic models to support rare disease diagnosis. All the diagnostic models were validated using the real medical records from RAMEDIS. Each model provides a list of the top 10 candidate diseases as the prediction outcome and the results showed that all models had a high diagnostic precision (≥98%) with the highest recall reaching up to 95% while the models with machine learning methods showed the best performance. To promote effective diagnosis for rare disease in clinical application, we developed the phenotype-based Rare Disease Auxiliary Diagnosis system (RDAD) to assist clinicians in diagnosing rare diseases with the above four diagnostic models. The system is freely accessible through http://www.unimd.org/RDAD/

The intermediary players affect the altruism behavior on the bipartite network

A myriad of participants in the market without direct interactions could act in a coordinated way thanks to the extremely hierarchical and diversified social structures developed spontaneously based on the economic mechanism. This paper investigates the function of the intermediary nodes on the network that may affect the altruistic behavior of the neighbours in the evolutionary games. To achieve this, a pairwise game is proposed on the bipartite graph inspired by the public goods game, where two layers of nodes are defined: the player nodes as the game participants, and the group nodes as the intermediary hubs. Specifically, a tolerance parameter is introduced to modify the behavior of the group nodes, which theoretically raises the surviving threshold of cooperators if sufficiently large. However, a double-edged effect is observed in the experiments where large values of the parameter are applied, which on the one hand helps the cooperators to survive, while it prevents the total elimination of exploiters, indicating the complex relevance between the roles of the intermediary nodes and the system behavior

Small RNA-based antimicrobial immunity.

Protection against microbial infection in eukaryotes is provided by diverse cellular and molecular mechanisms. Here, we present a comparative view of the antiviral activity of virus-derived small interfering RNAs in fungi, plants, invertebrates and mammals, detailing the mechanisms for their production, amplification and activity. We also highlight the recent discovery of viral PIWI-interacting RNAs in animals and a new role for mobile host and pathogen small RNAs in plant defence against eukaryotic pathogens. In turn, viruses that infect plants, insects and mammals, as well as eukaryotic pathogens of plants, have evolved specific virulence proteins that suppress RNA interference (RNAi). Together, these advances suggest that an antimicrobial function of the RNAi pathway is conserved across eukaryotic kingdoms