Chi-Tin Shih

Three-Dimensional Reconstruction of Brain-wide Wiring Networks in Drosophila at Single-Cell Resolution

BACKGROUND Animal behavior is governed by the activity of interconnected brain circuits. Comprehensive brain wiring maps are thus needed in order to formulate hypotheses about information flow and also to guide genetic manipulations aimed at understanding how genes and circuits orchestrate complex behaviors. RESULTS To assemble this map, we deconstructed the adult Drosophila brain into approximately 16,000 single neurons and reconstructed them into a common standardized framework to produce a virtual fly brain. We have constructed a mesoscopic map and found that it consists of 41 local processing units (LPUs), six hubs, and 58 tracts covering the whole Drosophila brain. Despite individual local variation, the architecture of the Drosophila brain shows invariance for both the aggregation of local neurons (LNs) within specific LPUs and for the connectivity of projection neurons (PNs) between the same set of LPUs. An open-access image database, named FlyCircuit, has been constructed for online data archiving, mining, analysis, and three-dimensional visualization of all single neurons, brain-wide LPUs, their wiring diagrams, and neural tracts. CONCLUSION We found that the Drosophila brain is assembled from families of multiple LPUs and their interconnections. This provides an essential first step in the analysis of information processing within and between neurons in a complete brain.

Connectomics-Based Analysis of Information Flow in the Drosophila Brain

Understanding the overall patterns of information flow within the brain has become a major goal of neuroscience. In the current study, we produced a first draft of the Drosophila connectome at the mesoscopic scale, reconstructed from 12,995 images of neuron projections collected in FlyCircuit (version 1.1). Neuron polarities were predicted according to morphological criteria, with nodes of the network corresponding to brain regions designated as local processing units (LPUs). The weight of each directed edge linking a pair of LPUs was determined by the number of neuron terminals that connected one LPU to the other. The resulting network showed hierarchical structure and small-world characteristics and consisted of five functional modules that corresponded to sensory modalities (olfactory, mechanoauditory, and two visual) and the pre-motor center. Rich-club organization was present in this network and involved LPUs in all sensory centers, and rich-club members formed a putative motor center of the brain. Major intra- and inter-modular loops were also identified that could play important roles for recurrent and reverberant information flow. The present analysis revealed whole-brain patterns of network structure and information flow. Additionally, we propose that the overall organizational scheme showed fundamental similarities to the network structure of the mammalian brain.

Point-mutation effects on charge-transport properties of the tumor-suppressor gene p53

We report on a theoretical study of point mutations effects on charge transfer properties in the DNA sequence of the tumor-suppressor p53 gene. On the basis of effective tight-binding models which simulate hole propagation along the DNA, a statistical analysis of mutation-induced charge transfer modifications is performed. In contrast to noncancerous mutations, mutation hot spots tend to result in significantly weaker changes of transmission properties. This suggests that charge transport could play a significant role for DNA-repairing deficiency yielding carcinogenesis.

Low-energy physical properties of high-T-c superconducting Cu oxides: A comparison between the resonating valence bond and experiments

In a recent review by Anderson and co-workers, it was pointed out that an early resonating valence bond (RVB) theory is able to explain a number of unusual properties of high-temperature superconducting (SC) Cu oxides. Here we extend previous calculations to study more systematically the low-energy physical properties of the plain vanilla d-wave RVB state, and to compare the results with the available experiments. We use a renormalized mean-field theory combined with variational Monte Carlo and power Lanczos methods to study the RVB state of an extended t-J model in a square lattice with parameters suitable for the hole-doped Cu oxides. The physical observable quantities we study include the specific heat, the linear residual thermal conductivity, the in-plane magnetic penetration depth, the quasiparticle energy at the antinode (pi,0), the superconducting energy gap, the quasiparticle spectra, and the Drude weights. The traits of nodes (including k(F), the Fermi velocity v(F), and the velocity along Fermi surface v(2)), and the SC order parameter are studied. Comparisons of the theory and the experiments in cuprates show an overall qualitative agreement, especially on their doping dependences.

D-WAVE PAIRING CORRELATION IN THE TWO-DIMENSIONAL T-J MODEL

The pair-pair correlation function of the two-dimensional t-J model is studied by using the power-Lanczos method and an assumption of monotonic behavior. In comparison with the results of the ideal Fermi gas, we conclude that the 2D t-J model does not have long range d-wave superconducting correlation in the interesting parameter range of

MODELLING CHARGE TRANSPORT IN DNA USING TRANSFER MATRICES WITH DIAGONAL TERMS

J/t \leq 0.5

Antiferromagnetism and superconductivity of the two-dimensional extended t-J model

. Implications of this result will also be discussed.

The interplay of mutations and electronic properties in disease-related genes

There is increasing evidence that DNA can support a considerable degree of charge transport along the strand by hopping of holes from one base to another, and that this charge transport may be relevant to DNA regulation, damage detection and repair. A surprisingly useful amount of insight can be gained from the construction of simple tight-binding models of charge transport, which can be investigated using the transfer-matrix method. The data thus obtained indicate a correlation between DNA charge-transport properties and the locations of cancerous mutation. We review models for DNA charge transport and their extension to include more physically realistic diagonal-hopping terms.

Charge Transport in Cancer-Related Genes and Early Carcinogenesis

The mechanism of high-temperature superconductivity (HTS) and the correlation between the antiferromagnetic long-range order (AFLRO) and superconductivity (SC) are the central issues of the study of HTS theory. SC and AFLRO of the hole-doped two-dimensional extended t-J model are studied by the variational Monte Carlo method. The results show that SC is greatly enhanced by the long-range hopping terms t′ and t″ for the optimal and overdoped cases. The phase of coexisting SC and AFM in the t-J model disappears when t′ and t″ are included. It is concluded that the extended t-J model provides a more accurate description for HTS than the traditional t-J model does. The momentum distribution function n(k) and the shape of Fermi surface play critical roles for establishing the phase diagram of HTS materials.

The Topographical Mapping in Drosophila Central Complex Network and Its Signal Routing

Electronic properties of DNA are believed to play a crucial role in many phenomena in living organisms, for example the location of DNA lesions by base excision repair (BER) glycosylases and the regulation of tumor-suppressor genes such as p53 by detection of oxidative damage. However, the reproducible measurement and modelling of charge migration through DNA molecules at the nanometer scale remains a challenging and controversial subject even after more than a decade of intense efforts. Here we show, by analysing 162 disease-related genes from a variety of medical databases with a total of almost 20,000 observed pathogenic mutations, a significant difference in the electronic properties of the population of observed mutations compared to the set of all possible mutations. Our results have implications for the role of the electronic properties of DNA in cellular processes, and hint at the possibility of prediction, early diagnosis and detection of mutation hotspots.