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Articles by Wenling Li in JoVE

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Whole-mount עבור ניתוח immunohistochemical vasculature לימב עובריים עור: מערכת מודל לחקר המורפוגנזה מסעף דם בעובר


JoVE 2620 5/20/2011

Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health

אנחנו מציגים אימונוהיסטוכימיה כל הר לייזר מיקרוסקופיית confocal עם תיוג מרובים לניתוח רשת סבוכה היווצרות כלי דם בעור איבר עכבר עובריים.

Other articles by Wenling Li on PubMed

[Examining Consecutively Serum Leptin Levels in Normal Pregnant and Pregnancy-induced Hypertension Women]

To detect successsively serum leptin levels in normal, pregnancy-induced hypertension (PIH) pregnant women.

Total Synthesis of (+/-)-quadrangularin A

Development of Phonological Awareness in Bilingual Chinese Children

This study investigated the phonological awareness of 219 first, second, and fourth grade Cantonese-speaking children from the south of China, who received immersion Mandarin instruction beginning in the first grade. Children received onset, rime and tone awareness tasks in Cantonese and Mandarin. Children performed better on the Cantonese onset awareness task in grade one, but the difference disappeared in higher grades. However, their performance on the rime and tone awareness tasks was better in Mandarin. These results reflect the phonological structure of the two languages: Mandarin has a more complex onset system, whereas Cantonese has more complex tone and rime systems. Moreover, children's phonological awareness increased faster in Mandarin, which likely resulted from Mandarin instruction. Confirmatory factor analysis suggested that onset-rime awareness is a universal construct, whereas tone awareness is a language-specific construct.

Nf1 Mutation Expands an EGFR-dependent Peripheral Nerve Progenitor That Confers Neurofibroma Tumorigenic Potential

Defining growth factor requirements for progenitors facilitates their characterization and amplification. We characterize a peripheral nervous system embryonic dorsal root ganglion progenitor population using in vitro clonal sphere-formation assays. Cells differentiate into glial cells, smooth muscle/fibroblast (SM/Fb)-like cells, and neurons. Genetic and pharmacologic tools revealed that sphere formation requires signaling from the EGFR tyrosine kinase. Nf1 loss of function amplifies this progenitor pool, which becomes hypersensitive to growth factors and confers tumorigenesis. DhhCre;Nf1(fl/fl) mouse neurofibromas contain a progenitor population with similar growth requirements, potential, and marker expression. In humans, NF1 mutation predisposes to benign neurofibromas, incurable peripheral nerve tumors. Prospective identification of human EGFR(+);P75(+) neurofibroma cells enriched EGF-dependent sphere-forming cells. Neurofibroma spheres contain glial-like progenitors that differentiate into neurons and SM/Fb-like cells in vitro and form benign neurofibroma-like lesions in nude mice. We suggest that expansion of an EGFR-expressing early glial progenitor contributes to neurofibroma formation.

Probing a Sialyltransferase's Recognition Domain to Prepare Alpha(2,8)-linked Oligosialosides and Analogs

We report the first observation that a monosialyl residue is the essential structural element recognized by the enzyme CST-II; this has resulted in an attractive route to synthesize a series of alpha(2,8)-linked oligosialic acids and their thioanalogs in one step.

Genistein Inhibition of Topoisomerase IIalpha Expression Participated by Sp1 and Sp3 in HeLa Cell

Genistein (4', 5, 7-trihydroxyisoflavone) is an isoflavone compound obtained from plants that has potential applications in cancer therapy. However, the molecular mechanism of the action of genistein on cancer cell apoptosis is not well known. In this study, we investigated the effect of genistein on topoisomerase II-alpha (Topo IIalpha), an important protein involved in the processes of DNA replication and cell proliferation. The results revealed that inhibition of Topo IIalpha expression through the regulation of Specificity protein 1 and Specificity protein 3 may be one of the reasons for genistein's induction of HeLa cell apoptosis.

Concise Synthesis of Cannabisin G

Cannabisin G (1), a naturally occurring lignanamide, was synthesized in 45% overall yield starting from 3-tert-butyl ethyl ferulate (6). An oxidative coupling by potassium ferricyanide in an alkaline media serves as the key step to construct the biphenylbutadiene skeleton of 1 with high regioselectivity.

Conditional Deletion of Ccm2 Causes Hemorrhage in the Adult Brain: a Mouse Model of Human Cerebral Cavernous Malformations

Cerebral cavernous malformations (CCM) are irregularly shaped and enlarged capillaries in the brain that are prone to hemorrhage, resulting in headaches, seizures, strokes and even death in patients. The disease affects up to 0.5% of the population and the inherited form has been linked to mutations in one of three genetic loci, CCM1, CCM2 and CCM3. To understand the pathophysiology underlying the vascular lesions in CCM, it is critical to develop a reproducible mouse genetic model of this disease. Here, we report that limited conditional ablation of Ccm2 in young adult mice induces observable neurological dysfunction and reproducibly results in brain hemorrhages whose appearance is highly reminiscent of the lesions observed in human CCM patients. We first demonstrate that conventional or endothelial-specific deletion of Ccm2 leads to fatal cardiovascular defects during embryogenesis, including insufficient vascular lumen formation as well as defective arteriogenesis and heart malformation. These findings confirm and extend prior studies. We then demonstrate that the inducible deletion of Ccm2 in adult mice recapitulates the CCM-like brain lesions in humans; the lesions display disrupted vascular lumens, enlarged capillary cavities, loss of proper neuro-vascular associations and an inflammatory reaction. The CCM lesions also exhibit damaged neuronal architecture, the likely cause of neurologic defects, such as ataxia and seizure. These mice represent the first CCM2 animal model for CCM and should provide the means to elucidate disease mechanisms and evaluate therapeutic strategies for human CCM.

CST-II's Recognition Domain for Acceptor Substrates in α-(2→8)-sialylations

CST-II is a bacterial sialyltransferase known for its ability to perform α-(2→8)-sialylations using GM(3) related trisaccharide substrates. Previously, we probed the enzyme's substrate specificity and developed an efficient synthesis for α-(2→8)-oligosialosides, and we suggested that CST-II could have a very small substrate recognition domain. Here we report our full studies on CST-II's recognition feature for acceptor substrates. The current study further demonstrates the versatility of CST-II in preparing complex oligosaccharides that contain α-(2→8)-oligosialyl moieties.

Synthesis of a Novel Class of Cyclodextrin-based Nanotubes

The synthesis and characterization of a novel class of structurally well-defined nanotubes from β-cyclodextrin are described. These new hosts were formed using disulfide linkages that substitute all the primary hydroxyl groups of a β-cyclodextrin. A deep and rigid hydrophobic channel with a size of more than 1.5 nm is found in the molecules. Because of their unique geometry and the potential biodegradability of the disulfide bond, this class of molecules could find broad applications in biology and other areas of research.

Rspo1/Wnt Signaling Promotes Angiogenesis Via Vegfc/Vegfr3

Here, we show that a novel Rspo1-Wnt-Vegfc-Vegfr3 signaling pathway plays an essential role in developmental angiogenesis. A mutation in R-spondin1 (rspo1), a Wnt signaling regulator, was uncovered during a forward-genetic screen for angiogenesis-deficient mutants in the zebrafish. Embryos lacking rspo1 or the proposed rspo1 receptor kremen form primary vessels by vasculogenesis, but are defective in subsequent angiogenesis. Endothelial cell-autonomous inhibition of canonical Wnt signaling also blocks angiogenesis in vivo. The pro-angiogenic effects of Rspo1/Wnt signaling are mediated by Vegfc/Vegfr3(Flt4) signaling. Vegfc expression is dependent on Rspo1 and Wnt, and Vegfc and Vegfr3 are necessary to promote angiogenesis downstream from Rspo1-Wnt. As all of these molecules are expressed by the endothelium during sprouting stages, these results suggest that Rspo1-Wnt-VegfC-Vegfr3 signaling plays a crucial role as an endothelial-autonomous permissive cue for developmental angiogenesis.

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