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   Web address:
     http://www.sciencedaily.com/releases/2008/11/
     081110153621.htm     
Key Mechanism That Regulates Development Of Stem Cells Into Neurons Identified

Researchers are now expanding their work to include studies of differentiation 
of human embryonic stem cells into neural stem cells and neurons. (Credit: 
iStockphoto/Chris Dascher)

ScienceDaily (Nov. 11, 2008) — Researchers at the University of Southern 
California (USC) have identified a novel mechanism in the regulation and 
differentiation of neural stem cells.

Researchers found that the protein receptor Ryk has a key role in the 
differentiation of neural stem cells, and demonstrated a signaling mechanism 
that regulates neuronal differentiation as stem cells begin to grow into 
neurons. The study will be published in the Nov. 11 issue of the journal 
Developmental Cell, and is now available online.

The findings could have important implications for regenerative medicine and 
cancer therapies, says Wange Lu, Ph.D., assistant professor of biochemistry and 
molecular biology at the Keck School of Medicine of USC, and the principal 
investigator on the study.

"Neural stem cells can potentially be used for cell-replacement therapy for 
neurodegenerative diseases such as Alzheimer's and Parkinson's Disease, as well 
as spinal cord injury," Lu says. "Knowledge gained from this study will 
potentially help to generate neurons for such therapy. This knowledge can also 
be used to inhibit the growth of brain cancer stem cells."

During brain development, neural stem cells respond to the surrounding 
environment by either proliferation or differentiation, but the molecular 
mechanisms underlying the development of neural stem cells and neurons are 
unclear, Lu notes.

Ryk functions as a receptor of Wnt proteins required for cell-fate 
determination, axon guidance and neurite outgrowth in organisms. Researchers at 
the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell 
Research at USC analyzed sections of the forebrain in animal model embryos to 
investigate Ryk's function in vivo.

They found that during neurogenesis, when neural stem cells start to grow into 
neurons, Ryk protein is cleaved and translocates to the cell nucleus to 
regulate neuronal differentiation.

This finding is extremely important for understanding the regulation of 
self-renewal and differentiation of neural stem cells, Lu says. Previous 
research has shown that Ryk functions as a receptor of Wnt proteins. However, 
the role of Ryk in neural stem cells and the molecular mechanism of Ryk 
signaling have not previously been known.

"This study will help in our efforts to produce nerve cells from embryonic stem 
cells, and may lead to the development of new strategies for the repair of the 
nervous system, using protein or small molecule therapeutic agents," says 
Martin Pera, Ph.D., director of the Eli and Edythe Broad Center for 
Regenerative Medicine and Stem Cell Research at USC.

Further research is needed to explore how Ryk regulates neuronal gene 
expression, Lu says. Researchers are now expanding their research to studies of 
differentiation of human embryonic stem cells into neural stem cells and 
neurons. These studies are very important for regenerative medicine and drug 
discovery for therapy of neurodegenerative diseases.

The study was funded by the Baxter Foundation and the American Cancer Society. 
The current studies using human ES cells are being funded by a CIRM SEED grant.

Journal reference:

   1. Jungmook Lyu, Vicky Yamamoto and Wange Lu. Cleavage of Wnt Receptor Ryk 
Regulates Neuronal Differentiation during Cortical Neurogenesis. Developmental 
Cell, Nov. 2008

Adapted from materials provided by University of Southern California. Original 
article written by Meghan Lewit.
Need to cite this story in your essay, paper, or report? Use one of the 
following formats:
APA

MLA
University of Southern California (2008, November 11). Key Mechanism That 
Regulates Development Of Stem Cells Into Neurons Identified. ScienceDaily. 
Retrieved November 12, 2008, from http://www.sciencedaily.com­ 
/releases/2008/11/081110153621.htm


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