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JCI online early table of contents: Jan. 4, 2011
Date:1/4/2011

also known as Lou Gehrig's disease) and frontotemporal lobar degeneration (FTLD) are clinically quite distinct, although a few patients have some overlapping symptoms. However, both conditions are characterized by aggregates that contain the protein TDP-43 in the cytoplasm (the jelly-like substance that fills the cell) of nerve cells in the brain and spinal cord. Surprisingly, Virginia Lee and colleagues, at the University of Pennsylvania School of Medicine, Philadelphia, have now determined, using mice expressing either normal human TDP-43 or a mutant form of human TDP-43 that localized to the cytoplasm rather than the nucleus (the normal location for the protein), that the presence of TDP-43 cytoplasmic aggregates do not correlate with nerve cell death. Rather, nerve cell death correlated with loss of mouse TDP-43 in the nucleus, which led to profound alterations in gene expression. These data provide new insight into the link between TDP-43 and neurological disease.

TITLE: Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice

AUTHOR CONTACT:
Virginia M.-Y. Lee
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: 215.662.6427; Fax: 215.349.5909; E-mail: vmylee@mail.med.upenn.edu.

View this article at: http://www.jci.org/articles/view/44867?key=5fcbdccd59ebc8a3542e


VIROLOGY: The protein A20 an impediment to HIV immunity

Preventing and/or containing HIV transmission requires immune responses throughout the body (i.e., systemic immune responses) and at the site of infection (i.e., mucosal surfaces such as the lining of the vagina). Ideal HIV vaccines should activate both of these immune responses, but approaches currently under development rarely do. A team of researchers, led by Si-Yi Chen an
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Journal of Clinical Investigation
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