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Biomedical subjects

Li Cai

Publications and source records attributed to Li Cai.

28 records · Page 2Linked to original sources

Genomic analysis of mouse retinal development.

The vertebrate retina is comprised of seven major cell types that are generated in overlapping but well-defined intervals. To identify genes that might regulate retinal development, gene expression in the developing retina was profiled at multiple time points using serial analysis of gene expression (SAGE). The expression patterns of 1,051 genes that showed developmentally dynamic expression by SAGE were investigated using in situ hybridization. A molecular atlas of gene expression in the developing and mature retina was thereby constructed, along with a taxonomic classification of developmental gene expression patterns. Genes were identified that label both temporal and spatial subsets of mitotic progenitor cells. For each developing and mature major retinal cell type, genes selectively expressed in that cell type were identified. The gene expression profiles of retinal Müller glia and mitotic progenitor cells were found to be highly similar, suggesting that Müller glia might serve to produce multiple retinal cell types under the right conditions. In addition, multiple transcripts that were evolutionarily conserved that did not appear to encode open reading frames of more than 100 amino acids in length ("noncoding RNAs") were found to be dynamically and specifically expressed in developing and mature retinal cell types. Finally, many photoreceptor-enriched genes that mapped to chromosomal intervals containing retinal disease genes were identified. These data serve as a starting point for functional investigations of the roles of these genes in retinal development and physiology.

Animals↗

Molecular characterization of the tumor microenvironment in breast cancer.

Here we describe the comprehensive gene expression profiles of each cell type composing normal breast tissue and in situ and invasive breast carcinomas using serial analysis of gene expression. Based on these data, we determined that extensive gene expression changes occur in all cell types during cancer progression and that a significant fraction of altered genes encode secreted proteins and receptors. Despite the dramatic gene expression changes in all cell types, genetic alterations were detected only in cancer epithelial cells. The CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and myofibroblasts, respectively, bind to receptors on epithelial cells and enhance their proliferation, migration, and invasion. Thus, chemokines may play a role in breast tumorigenesis by acting as paracrine factors.

Biomarkers, Tumor↗

Cardiac conductive system excitation maps using intracardiac tissue Doppler imaging.

OBJECTIVE: To precisely visualize cardiac anatomic structures and simultaneously depict electro-mechanical events for the purpose of precise underblood intervention. METHODS: Intracardiac high-resolution tissue Doppler imaging was used to map real time myocardial contractions in response to electrical activation within the anatomic structure of the cardiac conductive system using a canine open-chest model. RESULTS: The detailed inner anatomic structure of the cardiac conductive system at different sites (i.e., sino-atrial, atrial wall, atrial-ventricular node and ventricular wall) with the inside onset and propagation of myocardial velocity and acceleration induced by electrical activation was clearly visualized and quantitatively evaluated. CONCLUSION: The simultaneous single modality visualization of the anatomy, function and electrical events of the cardiac conductive system will foster target pacing and precision ablation.

Animals↗

Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior.

Mechanisms that regulate neuron production in the developing mouse neocortex were examined by using a retroviral lineage marking method to determine the sizes of the lineages remaining in the proliferating population of the ventricular zone during the period of neuron production. The distribution of clade sizes obtained experimentally in four different injection-survival paradigms (E11-E13, E11-E14, E11-E15, and E12-E15) from a total of over 500 labeled lineages was compared with that obtained from three models in which the average behavior of the proliferating population [i.e., the proportion of cells remaining in the proliferative population (P) vs. that exiting the proliferative population (Q)] was quantitatively related to lineage size distribution. In model 1, different proportions of asymmetric, symmetric terminal, and symmetric nonterminal cell divisions coexisted during the entire developmental period. In model 2, the developmental period was divided into two epochs: During the first, asymmetric and symmetric nonterminal cell divisions occurred, but, during the second, asymmetric and symmetric terminal cell divisions occurred. In model 3, the shifts in P and Q are accounted for by changes in the proportions of the two types of symmetric cell divisions without the inclusion of any asymmetric cell divisions. The results obtained from the retroviral experiments were well accounted for by model 1 but not by model 2 or 3. These findings demonstrate that: 1) asymmetric and both types of symmetric cell divisions coexist during the entire period of neurogenesis in the mouse, 2) neuron production is regulated in the proliferative population by the independent decisions of the two daughter cells to reenter S phase, and 3) neurons are produced by both asymmetric and symmetric terminal cell divisions. In addition, the findings mean that cell death and/or tangential movements of cells in the proliferative population occur at only a low rate and that there are no proliferating lineages "reserved" to make particular laminae or cell types.

Animals↗

Efficacy of SSH PCR in isolating differentially expressed genes.

BACKGROUND: Suppression Subtractive Hybridization PCR (SSH PCR) is a sophisticated cDNA subtraction method to enrich and isolate differentially expressed genes. Despite its popularity, the method has not been thoroughly studied for its practical efficacy and potential limitations. RESULTS: To determine the factors that influence the efficacy of SSH PCR, a theoretical model, under the assumption that cDNA hybridization follows the ideal second kinetic order, is proposed. The theoretical model suggests that the critical factor influencing the efficacy of SSH PCR is the concentration ratio (R) of a target gene between two cDNA preparations. It preferentially enriches "all or nothing" differentially expressed genes, of which R is infinite, and strongly favors the genes with large R. The theoretical predictions were validated by our experiments. In addition, the experiments revealed some practical limitations that are not obvious from the theoretical model. For effective enrichment of differentially expressed genes, it requires fractional concentration of a target gene to be more than 0.01% and concentration ratio to be more than 5 folds between two cDNA preparations. CONCLUSION: Our research demonstrated theoretical and practical limitations of SSH PCR, which could be useful for its experimental design and interpretation.

Journal Article↗

Ena/VASP proteins regulate cortical neuronal positioning.

Development of the multilayered cerebral cortex involves extensive regulated migration of neurons arising from the deeper germinative layers of the mammalian brain. The anatomy and formation of the cortical layers has been well characterized; however, the underlying molecular mechanisms that control the migration and the final positioning of neurons within the cortex remain poorly understood. Here, we report evidence for a key role of Ena/VASP proteins, a protein family implicated in the spatial control of actin assembly and previously shown to negatively regulate fibroblast cell speeds, in cortical development. Ena/VASP proteins are highly expressed in the developing cortical plate in cells bordering Reelin-expressing Cajal-Retzius cells and in the intermediate zone through which newly born cells migrate. Inhibition of Ena/VASP function through retroviral injections in utero led to aberrant placement of early-born pyramidal neurons in the superficial layers of both the embryonic and the postnatal cortex in a cell-autonomous fashion. The abnormally placed pyramidal neurons exhibited grossly normal morphology and polarity. Our results are consistent with a model in which Ena/VASP proteins function in vivo to control the position of neurons in the mouse neocortex.

Animals↗

[Prevention and control of intestinal nematode infection in Shanghai].

OBJECTIVE: To evaluate the current status of intestinal nematode infection in Shanghai and make recommendations for further control activities. METHODS: Retrospective review of the control program was made based on the change of nematode prevalence in Shanghai area since the 1950s, and challenges under the current situation were analysed. RESULTS: The intervention measures included chemotherapy, health education, sanitary disposal of human excreta and safe water supply. With the control strategy, socio-economical development and the change of farming patterns, the prevalence of intestinal nematode infection in population was reduced by 88.5%, from 62.6% in 1955 to 8.2% in 2000. Among them, ascaris infection decreased by 89.0%, from 52.1% to 6.3%, hookworm infection decreased by 99.0%, from 12.9% to 0.1%, but pinworm infection was still as high as 18.9% in 1999. CONCLUSION: Prevalence of nematode infection in Shanghai was considerably reduced. To match it with the current socio-economical development in the Municipality, however, more needs to be done. Sustainable control activities and surveillance are recommended.

China↗