Evolutionary patterns in snake mitochondrial genomes

In this dissertation I describe a number of patterns and interesting aspects associated with the evolution of snake mitochondrial genomes (mtDNA). I also attempt to resolve the phylogeny of squamates, focusing on the relationship between the snakes and lizards. The results of this study indicate that snakes and worm lizards (amphisbaenians) appear to share an exclusive common ancestor, and snakes appear to have undergone strong selective pressure that shaped snake mtDNAs. Snake mtDNAs have several unique features, including a compact size, duplicated control regions, and an elevated evolutionary rate. Based on the correlation resulting from the asymmetric replication of mtDNA, the usage of control regions was inferred to be species specific. In snake mtDNAs, the magnitude of the rate acceleration varied considerably among genes and over time, and it appears that these changes at the nucleotide and protein level co-occurred with snake mtDNAs incurring a reduction in size and a duplication of the control region. In snake mtDNA, many unique amino acid substitutions were identified in all protein-coding genes. In the Cytochrome C Oxidase subunit I (COX1) protein, one of three proposed proton transfer channels was enhanced by several unique substitutions. Additionally, strong positive selection was detected on the COX1 gene of alethinophidian snakes. These may be causally related to the energetic demands imposed by the radical energy requirement in the early digestion period of alethinophidian snakes. Observations of change in COX1 gene suggest that, due to the relaxation of selective pressure or a population bottleneck, numerous deleterious substitutions accumulated on snake ancestral lineages. Then the impaired functions were recovered, or even enhanced by adaptation. During this period, the evolutionary rate of snakes was accelerated as well. In this research, the phylogenetic placement of snakes was inferred using the complete mtDNA of 65 vertebrates by maximum likelihood (ML) and partitioned-Bayesian inference. Snakes were placed as the sister taxon to worm lizards, and this branching pattern is strongly supported by Bayesian inference-derived posterior probability. The jackknife simulation also supports the sister relationship between snakes and worm lizards, cumulatively rejecting the hypothesis of marine origins of snakes

Developing a Knowledge-based System for Complex Geometrical Product Specification (GPS) Data Manipulation.

Geometrical product specification and verification (GPS) matrix system is a universal tool for expressing geometrical requirements on product design drawings. It benefits product designers through providing detailed description of functional requirements for geometrical products, and through referring to corresponding manufacturing and verification processes. In order to overcome current implementation problems highlighted in this paper, a GPS knowledge base and a corresponding innovative inference mechanism have been researched, which led to the development of an integrated GPS knowledge-based system to facilitate rapid and flexible manufacturing requirements. This paper starts with a brief introduction of GPS, GPS application problems and the project background. It then moves on to demonstrate a unified knowledge acquisition and representation mechanism based on the category theory (CT) with five selected examples of this project. The paper concludes with a discussion on the future works for this projec

RFWD3 acts as a tumor promotor in the development and progression of bladder cancer

Background. Bladder cancer is one of the most commonly diagnosed malignancies of the urinary system with relatively poor prognosis and insufficient treatment strategies. RFWD3 is an E3 ligase whose function is rarely investigated in malignant tumors. Methods. A tissue microarray was used for evaluating RFWD3 expression in clinical samples and its correlation with tumor characteristics and patients’ prognosis. RFWD3 knockdown and overexpression cell models were constructed for conducting loss-of-function and gain-of-function assays. qPCR and western blotting were used for detecting mRNA and protein levels of RFWD3, respectively. MTT assay, colony formation assay, flow cytometry, wound-healing assay and transwell assay were carried out to demonstrate the change of cell phenotypes upon RFWD3 knockdown. Results. RFWD3 expression was relatively higher in bladder cancer tissues than in normal tissues, which is correlated with higher N stage and poorer prognosis of patients. Knockdown of RFWD3 in bladder cancer cells significantly inhibited cell proliferation, colony formation, promote cell apoptosis and restrained cell migration. Overexpression of RFWD3 induced the opposite effects. Conclusions. It was illustrated that RFWD3 possesses excellent tumor-promoting ability in bladder cancer. Accordingly, RFWD3 may be a promising therapeutic target in the targeted therapy of bladder cancer, which is worth further research

Adiponectin protects against paraquat-induced lung injury by attenuating oxidative/nitrative stress.

The specific mechanisms underlying paraquat (PQ)-induced lung injury remain unknown, which limits understanding of its cytotoxic potential. Although oxidative stress has been established as an important mechanism underlying PQ toxicity, multiple antioxidants have proven ineffective in attenuating the deleterious effects of PQ. Adiponectin, which shows anti-oxidative and antinitrative effects, may have the potential to reduce PQ-mediated injury. The present study determined the protective action of globular domain adiponectin (gAd) on PQ-induced lung injury, and attempted to elucidate the underlying mechanism or mechanisms of action. BALB/c mice were administered PQ, with and without 12 or 36 h of gAd pre-treatment. The pulmonary oxidative/nitrative status was assessed by measuring pulmonary O2(•-), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and 8-hydroxy-2-dydeoxy guanosine (8-OHdG) production, and blood 3-Nitrotyrosine (3-NT). At a dose of 20 mg/kg, PQ markedly increased O2(•-), SOD, MDA, NO and 8-OHdG production 3 h post-administration, but did not significantly increase 3-NT levels until 12 h. gAd inhibited these changes in a dose-dependent manner, via transient activation of MDA, followed by attenuation of MDA formation from 6 h onwards. Histological analysis demonstrated that gAd decreased interstitial edema and inflammatory cell infiltration. These results suggest that gAd protects against PQ-induced lung injury by mitigating oxidative/nitrative stress. Furthermore, gAd may be a potential therapeutic agent for PQ-induced lung injury, and further pharmacological studies are therefore warranted

GenSensor Suite: A Web-Based Tool for the Analysis of Gene and Protein Interactions, Pathways, and Regulation

The GenSensor Suite consists of four web tools for elucidating relationships among genes and proteins. GenPath results show which biochemical, regulatory, or other gene set categories are over- or under-represented in an input list compared to a background list. All common gene sets are available for searching in GenPath, plus some specialized sets. Users can add custom background lists. GenInteract builds an interaction gene list from a single gene input and then analyzes this in GenPath. GenPubMed uses a PubMed query to identify a list of PubMed IDs, from which a gene list is extracted and queried in GenPath. GenViewer allows the user to query one gene set against another in GenPath. GenPath results are presented with relevant P- and q-values in an uncluttered, fully linked, and integrated table. Users can easily copy this table and paste it directly into a spreadsheet or document