A MYC INDUCED LONG NON-CODING RNA, DANCR, THAT AFFECTS CELL PROLIFERATION

Long non-coding RNAs (lncRNAs) are pervasively transcribed in the human genome and are known to be functioning in various cellular processes; however, the exact mechanisms involved are not well understood. The MYC proto-oncogene encodes a transcription factor that regulates cellular functions through the activation of its many RNA targets. In this thesis, I address the role of MYC-regulated lncRNAs in cancer. I first utilized experimental methods, such as microarray, RNA-seq, and TCGA analysis, to globally explore the regulatory role of MYC on lncRNAs. One lncRNA, DANCR, was identified as one of the most highly MYC-induced targets in human cancers. To further confirm that DANCR is directly regulated by MYC, I demonstrated by CHIP and CHIP-seq that MYC could bind directly to an E-box motif (CACGTG) in the DANCR promoter sequence. Using existing data and my own experimental analysis, DANCR expression was shown to be upregulated in most primary cancers. I next sought to determine whether DANCR is required for MYC-mediated cellular functions in cancer. Abrogation of DANCR expression using siRNA resulted in defective cell proliferation. Cell cycle analysis showed that the defect triggered by DANCR depletion was a consequence of G1 to S phase transition arrest. To assess the expression of genes responsible for this phenotype, I examined the expression profiles of cancer cells treated with DANCR siRNA. Gene Set Enrichment Analysis (GSEA) showed that a large subset of upregulated genes are common to DANCR- and EZH2-depletion. Moreover, p21, an important G1 phase cell cycle regulator, was found to be among those genes. I later showed that p21 could be suppressed by both DANCR and EZH2. More importantly, a double knock-down experiment of DANCR and p21 resulted in the partial rescue of the proliferation reduction caused by DANCR knock-down alone, providing evidence that p21 is one of the most important targets of DANCR. I proposed that MYC induces DANCR, which suppresses p21 via the EZH2 pathway, and then provided evidence for this model in a series of IP (immunoprecipitation) experiments to establish interactions between pathway components. A 3ʹ-domain of DANCR was shown to bind EZH2, whereas a 5ʹ-domain of DANCR recognized p21 nascent mRNA via RNA–RNA interactions, which guides DANCR–EZH2 complexes to the p21 locus. Finally, using computational approaches, I also attempted to explore whether my proposed mechanism could be generalized to other DANCR targets, and 8 out of 16 genes tested seemed to conform to this model. My findings elucidate an important missing ‘link’ in the MYC regulated gene network, showing active roles for lncRNAs in MYC-mediated cancer, which could be important targets for cancer diagnosis and therapy. Advisor: Dr. Chi Dang Readers: Drs. Stephen Baylin and Chi Dang Other Committee Members: Drs. John Isaacs and James Herma

π-Conjugated molecules with fused rings for organic field-effect transistors: design, synthesis and applications

π-Conjugated molecular materials with fused rings are the focus of considerable interest in the emerging area of organic electronics, since the combination of excellent charge carrier mobility and high stability may lead to their practical applications. This tutorial review discusses the synthesis, properties and applications of π-conjugated organic semiconducting materials, especially those with fused rings. The achievements to date, the remaining problems and challenges, and the key research that needs to be done in the near future are all discussed

Wearable Haptic Interfaces and Systems

The past two decades have seen significant advances in how users interact with machines. Yet nowadays, people are increasingly paying attention to developing new control terminals and interfaces regarding communication between humans and robots, special equipment, or the virtual world. Wearable haptic interfaces offer more comfortable and realistic interactive experiences in human-machine touch and satisfy people’s needs beyond simply controlling objects. They are now applied in various areas, including health, education, virtual reality, object detection, etc... The passage briefly introduces some familiar wearable haptic interfaces, including hand-worn, vest-worn, and foot-worn devices. And then the advantages and disadvantages of the mentioned wearable devices will also be discussed. This passage will provide an overview of the current technology in wearable haptic interfaces and help people understand the strengths and weaknesses of the devices for different body parts

Molecular analysis of Shigella boydii O1 O-antigen gene cluster and its PCR typing

Shigella is an important human pathogen and is closely related to Escherichia coli. O-antigen is the most variable part of the lipopolysaccharide on the cell surface of Gram-negative bacteria and plays an important role in pathogenicity. The O-antigen gene cluster of S. boydii O1 was sequenced. The putative genes encoding enzymes for rhamnose synthesis, transferases, O-unit flippase, and O-unit polymerase were identified on the basis of homology. The O-antigen gene clusters of S. boydii O1 and E. coli O149, which share the same O-antigen form, were found to have the same genes and organization by adjacent gene PCR assay. Two genes specific for S. boydii O1 and E. coli O149 were identified by PCR screening against E. coli- and Shigella-type strains of the 186 known O-antigen forms and 39 E. coli clinical isolates. A PCR sensitivity of 103 to 104 CFU/mL overnight culture of S. boydii O1 and E. coli O149 was obtained. S. boydii O1 and E. coli O149 were differentiated by PCR using lacZ- and cadA-based primers

Facile synthesis of azobenzene‐embedded conjugated macrocycles for optically switchable single‐crystal transistors and tunable supramolecular assemblies

Abstract A series of new π‐conjugated macrocycles (AzoM‐n‐E, n = 1–3) incorporating azobenzene units have been synthesized by a facile strategy in one‐pot reaction. The resultant azobenzene‐embedded macrocycles feature intrinsic photoresponsive behaviors and intriguing supramolecular assembling properties. The smallest macrocycle AzoM‐1‐E with a rigid planar conjugated backbone structure is used to prepare the single crystal transistors, showing reversible optical tunability. The moderate size macrocycle AzoM‐2‐E assembles into a dimer in the form of interpenetration through π‐π stacking between azobenzene units. The largest macrocycle AzoM‐3‐E with enhanced flexibility can adaptively assemble with various types of electron‐deficient guests accompanied by distortion of azobenzene. Typically, AzoM‐3‐E assembles with the planar F4‐TCNQ to form a tetragonal geometry by C‐F···π and π‐π interactions, while the assembly with ellipsoidal C70 via π‐π interactions induces AzoM‐3‐E to form a boat‐shaped geometry. This work will shed new light on the development of functional conjugated macrocycles in organic electronics

Using depression deposits to reconstruct human impact on sediment yields from a small karst catchment over the past 600 years

Assessment of long-term human impact on sediment yields from karst settings can improve our understanding of the pattern of soil erosion causing rocky desertification in the historical context of environmental change influenced by human activity. Few previous investigations have estimated this impact over time-scales longer than 50 years. This study used dated depression deposits to reconstruct human impact on sediment yields from a small karst catchment in the Three Gorges Reservoir Region, China, over the past 600 years. Cs-137, Pb-210(ex), and C-14 techniques were used to determine short-term (similar to 50 yr), medium-term (similar to 100 yr), and long-term (similar to 600 yr) sedimentation in the karst depression, respectively. Sedimentation rates and specific sediment yields in the catchment during six distinct stages (1351-1462, 1463-1701, 1702-1809, 1810-1916, 1917-1962, and 1963-2017) were determined from core samples. The results indicate that soil loss during the period 1351-1962 was more intensive than that since 1963, which reveals changing sediment yields impacted by human activity over the past 600 years. The high values during the three stages before 1810 can be attributed to the impacts of large-scale migration of people from Huguang to Sichuan during the Ming and Qing dynasties; the higher values during 1810-1916 might reflect increasing disturbance related to rapid population expansion; the highest values (1917-1962) were caused by large-scale deforestation in 1958 and a consistently increasing population; and low values since 1963 reflect constraints on the supply of sediment source materials. These results suggest that rocky desertification might be a long-term land-surface process induced by human activity over timescales of > 100 years rather than a short-term modern process occurring over a number of decades. This is the first attempt to examine the long-term history of human impact on sediment yields from a karat catchment using depression deposits. This work improves our understanding of the influence of human activities on soil loss at a depression-catchment scale, and of the evolution and dynamics of rocky desertification in karst areas

The clutch size, incubation behavior of Reeves's Pheasant (Syrmaticus reevesii) and their responses to ambient temperature and precipitation

Weather conditions play a pivotal role in embryo development and parental incubation costs, potentially impacting the clutch size and incubation behavior of birds. Understanding these effects is crucial for bird conservation. Reeves's Pheasant (Syrmaticus reevesii) is a threatened species endemic to China, which is characterized by female-only incubation. However, there is a lack of information regarding the impact of weather conditions on clutch size and incubation behavior in this species. Using satellite tracking, we tracked 27 wild female Reeves's Pheasants from 2020 to 2023 in Hubei Province, China. We explored their clutch size and incubation behavior, as well as their responses to ambient temperature and precipitation. Clutch size averaged 7.75 ± 1.36, had an association with average ambient temperature and average daily precipitation during the egg-laying period, and was potentially linked to female breeding attempts. Throughout the incubation period, females took an average of 0.73 ± 0.46 recesses every 24 h, with an average recess duration of 100.80 ± 73.37 min and an average nest attendance of 92.98 ± 5.27%. They showed a unimodal recess pattern in which nest departures peaked primarily between 13:00 and 16:00. Furthermore, females rarely left nests when daily precipitation was high. Recess duration and nest attendance were influenced by the interaction between daily mean ambient temperature and daily precipitation, as well as day of incubation. Additionally, there was a positive correlation between clutch size and recess duration. These results contribute valuable insights into the life-history features of this endangered species