Dissecting the Molecular Mechanisms Underlying Synpase Development and Neuronal Functions in Caenorhabditis elegans

The development and function of the nervous system is under delicate regulation of diverse tissue-derived signals in multi-cellular organisms. In Dr. Nonet\u27s lab, I am using the model organism Caenorhabditis elegans to ask two basic questions: 1) How do different tissues in an organism coordinate to regulate neural functions and behaviors? 2) What controls the development of synapse, the basic unit of the nervous system? These questions divide my dissertation into three parts, with the first two parts related to the first question and the third part to the second question. In the first part of this dissertation, I present work that demonstrates the role of the C. elegans intestine as an endocrine organ in regulating the rhythmic defecation behavior: Chapter 2). The C. elegans defecation behavior consists of three well-coordinated muscle contractions that enable the nematode to expel intestinal contents out to the environment. Genetic and cell biology analyses showed that the early and late muscle contractions involve activities in the intestine and GABAergic neurons: AVL and DVB), respectively, while it remains unclear how the intestinal event is coordinated with later activation of GABAergic neurons. Using molecular genetics and cell biology approaches, we demonstrate that the exocytic protein AEX-4 and proprotein convertase AEX-5 function in the worm intestine to control the defecation motor program. When expressed in the intestine, AEX-5 is secreted into the pseudocoelom, and this secretion is blocked by AEX-4 disruption. Moreover, we show that the G-protein coupled receptor: GPCR) AEX-2 functions in GABAergic neurons to regulate defecation behavior, and it is genetically downstream of intestinal AEX-4 and AEX-5 signals. We also demonstrate that the stimulatory Gα pathway relays the AEX-2 signal in GABAergic neurons. Together, our results provide evidence that the C. elegans intestine is able to modulate neuronal function by secretory signals. In the second part of this dissertation, I present work that demonstrates the role of the C. elegans intestine in modulating the cholinergic neurotransmission: Chapter 3). C. elegans utilizes acetylcholine as a neurotransmitter at its neuromuscular junctions: NMJs) to control muscle contractions and locomotion related behaviors. Using molecular genetics, pharmacological, and physiological approaches, we show that the proprotein convertase AEX-5 is required in the intestine to maintain normal cholinergic transmission in the nematode. In addition, we find that the GPCR AEX-2 functions in the GABAergic neurons to maintain cholinergic transmission level, and the stimulatory Gα pathway is genetically downstream of AEX-2. Interestingly, we find that although both the defecation motor program and the cholinergic transmission modulation involve intestinal signals and neuronal G-protein pathways, they depend on different downstream molecules: while the defecation requires GABA to activate the enteric muscle contraction in the last step of the defecation, the modulation of cholinergic transmission depends on neuropeptide processing enzymes EGL-3 and EGL-21. As GABAergic neurons do not directly synapse on cholinergic neurons in C. elegans, we speculate that the peptide signals act in a paracrine manner on cholinergic neurons. This suggests the C. elegans intestine could function as an endocrine organ to modulate multiple aspects of neuronal functions. In the last part of this dissertation, I focus on the early neural development of C. elegans and I present the preliminary work on the focal adhesion complex molecule ZYX-1 for its role in mechanosensory synapse development: Chapter 4). We cloned the zyx-1 allele from the genetic screen that looked for worms defective in PLM synaptic patch formation. Using time course imaging analysis of fluorescence labeled PLM neurons, we showed that zyx-1 mutants are able to form synapses during early development, while they fail to maintain the synapse to adulthood. In addition, we demonstrated that ZYX-1 acts cell-autonomously in mechanosensory neurons to regulate PLM synapse maintenance. I expect the identification of additional molecular players in the ZYX-1 pathway will shed light onto our understanding of the molecular mechanisms underlying synapse development

Colour Design for Carton-Packed Fruit Juice Packages

The present research studies the relationships between observers’ expectations for 7 fruit juice packages and the colour design of the package. To do this, a two-stage experiment was conducted. At the first stage, we studied perceived colours for the fruit images shown on each package. At the second stage, fruit juice packages with 20 package colours were rated using 5 bipolar scales: colour harmony, preference, freshness, naturalness and product quality. The experimental results show that the observers tended to perceive fruit image colours lighter and more saturated than those measured using colour measuring instruments. Using factor analyses, we classified the 5 bipolar scales into 2 factors: Product Preference and Freshness. Package colour design was found to have significant impacts on both factors: similarity in chroma and hue between package colour and perceived fruit colour would lead to high product expectations. Keywords: colour design; colour harmony; product expectation; perceived image colour</p

From Facial Parts Responses to Face Detection: A Deep Learning Approach

In this paper, we propose a novel deep convolutional network (DCN) that achieves outstanding performance on FDDB, PASCAL Face, and AFW. Specifically, our method achieves a high recall rate of 90.99% on the challenging FDDB benchmark, outperforming the state-of-the-art method by a large margin of 2.91%. Importantly, we consider finding faces from a new perspective through scoring facial parts responses by their spatial structure and arrangement. The scoring mechanism is carefully formulated considering challenging cases where faces are only partially visible. This consideration allows our network to detect faces under severe occlusion and unconstrained pose variation, which are the main difficulty and bottleneck of most existing face detection approaches. We show that despite the use of DCN, our network can achieve practical runtime speed.Comment: To appear in ICCV 201

Technology Fitness Landscape for Design Innovation: A Deep Neural Embedding Approach Based on Patent Data

Technology is essential to innovation and economic prosperity. Understanding technological changes can guide innovators to find new directions of design innovation and thus make breakthroughs. In this work, we construct a technology fitness landscape via deep neural embeddings of patent data. The landscape consists of 1,757 technology domains and their respective improvement rates. In the landscape, we found a high hill related to information and communication technologies (ICT) and a vast low plain of the remaining domains. The landscape presents a bird's eye view of the structure of the total technology space, providing a new way for innovators to interpret technology evolution with a biological analogy, and a biologically-inspired inference to the next innovation.Comment: 10 pages, 7 figure

Improving the Lattice QCD Hamiltonian

Improvement of the Hamiltonian in lattice gauge theory is considered. We give explicit expressions for classical improvement and discuss also quantum corrections.Comment: 3 pages, Latex. Presented at Lattice 97: 15th International Symposium on Lattice Field Theory, Edinburgh, Scotland, 22-26 Jul 1997, to appear in Nucl. Phys. B(Proc. Suppl.

The CDK8 Complex and Proneural Proteins Together Drive Neurogenesis from a Mesodermal Lineage

© 2017 Elsevier Ltd At least some animal species can generate neurons from mesoderm or endoderm, but the underlying mechanisms remain unknown. We screened for C. elegans mutants in which the presumptive mesoderm-derived I4 neuron adopts a muscle-like cell fate. From this screen, we identified HLH-3, the C. elegans homolog of a mammalian proneural protein (Ascl1) used for in vitro neuronal reprogramming, as required for efficient I4 neurogenesis. We discovered that the CDK-8 Mediator kinase module acts together with a second proneural protein, HLH-2, and in parallel to HLH-3 to promote I4 neurogenesis. Genetic analysis revealed that CDK-8 most likely promotes I4 neurogenesis by inhibiting the CDK-7/CYH-1 (CDK7/cyclin H) kinase module of the transcription initiation factor TFIIH. Ectopic expression of HLH-2 and HLH-3 together promoted expression of neuronal features in non-neuronal cells. These findings reveal that the Mediator CDK8 kinase module can promote non-ectodermal neurogenesis and suggest that inhibiting CDK7/cyclin H might similarly promote neurogenesis.National Institutes of Health (U.S.). Intramural Research Program (P40 OD010440)National Institutes of Health (U.S.) (GM24663)National Institutes of Health (U.S.) (HD75076