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JCI online early table of contents: Jan. 18, 2011

2011-01-19
(Press-News.org) EDITOR'S PICK: Selective estrogen signaling key to postmenopausal risk of obesity

The hormone estradiol-17-beta is a key reproductive hormone. However, it also contributes to the regulation of energy balance and body weight. As a result, estrogen deficiency following menopause is associated with an increased probability of obesity and increased risk for developing type 2 diabetes. A team of researchers, led by Jon Levine, at Northwestern University, Evanston, has now generated new insight into the mechanisms by which ER-alpha signaling maintains normal energy balance. Specifically, the team found that nonclassical ER-alpha signaling is key to the effects of estradiol-17-beta on energy balance. These data lead them to suggest that it might be possible to develop drugs that selectively activate nonclassical ER-alpha signaling to reduce the risks of obesity and metabolic disturbances in postmenopausal women.

TITLE: Genetic rescue of nonclassical ER-alpha signaling normalizes energy balance in obese Er-alpha-null mutant mice

AUTHOR CONTACT:
Jon E. Levine
Northwestern University, Evanston, Illinois, USA.
Phone: 847.491.7180; Fax: 847.491.5211; E-mail: jlevine@northwestern.edu.

View this article at: http://www.jci.org/articles/view/41702?key=e6c0c5e6b4574e440bcb

NEUROBIOLOGY: Propagating a characteristic of Parkinson disease

The nerve cells affected in individuals with Parkinson disease are characterized by the presence of structures known as Lewy bodies, which are primarily composed of aggregated α-synuclein (α-syn). Recent data, have suggested that α-syn can be transferred between neurons and that this propagates disease. A team of researchers, led by Patrik Brundin, at Lund University, Sweden, has now tested this hypothesis in several coculture systems and in vivo models, generating data that indicate that it is a key element in the progression of Parkinson disease pathology.

TITLE: Alpha-synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells

AUTHOR CONTACT:
Patrik Brundin
Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Phone: 46.46.222.05.29; Fax: 46.46.222.05.31; E-mail: patrik.brundin@med.lu.se.

View this article at: http://www.jci.org/articles/view/43366?key=468fe7ace80555577388

TRANSPLANTATION: Identifying the immune cell barrier to fetal stem cell transplantation

It is hoped that stem cell transplantation might provide a new approach to treat inherited disorders. However, this approach is currently limited by graft rejection and the need to persistently use immunosuppressive drugs to prevent graft rejection. Transplantation of genetically correct stem cells from a genetically nonidentical individual into the early gestational fetus, a treatment termed in utero hematopoietic cell transplantation (IUHCTx), could potentially overcome these limitations. However, clinical use of IUHCTx has been hampered by poor engraftment. Tippi MacKenzie, Qizhi Tang, and colleagues, at UCSF, San Francisco, have now determined that in mice maternal immune cells known as T cells are the main barrier to engraftment following IUHCTx. When the graft used for the IUHCTx was matched to the mother, engraftment was markedly enhanced, leading the authors to suggest that the clinical success of IUHCTx may be improved by transplanting cells matched to the mother.

TITLE: Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice

AUTHOR CONTACT:
Tippi C. MacKenzie
University of California, San Francisco, San Francisco, California, USA.
Phone: 415.476.4086; Fax: 415.476.2314; E-mail: Tippi.Mackenzie@ucsfmedctr.org.

Qizhi Tang
University of California, San Francisco, San Francisco, California, USA.
Phone: 415.476.1739; Fax: 415.502.8326; E-mail: Qizhi.Tang@ucsfmedctr.org.

View this article at: http://www.jci.org/articles/view/44907?key=03da42265642f0ef600c

TUMOR IMMUNOLOGY: New immune cell activator protects mice from cancer

Activation of immune cells known as iNKT cells has been shown to protect against cancer in animal models. In these studies, iNKT cell activation is achieved using a molecule known as alpha-GalCer and protection is mediated primarily by the immune molecule IFN-gamma. However, a team of researchers, led by Jay Berzofsky and Masaki Terabe, at the National Institutes of Health, Bethesda, has now identified a new iNKT cell activator that protects mice from tumors through an IFN-gamma–independent mechanism. As this new activator (beta-ManCer) synergized with alpha-GalCer to protect mice against tumors, the authors suggest that similar treatments may provide protection against tumors in humans.

TITLE: Mouse and human iNKT cell agonist beta-mannosylceramide reveals a distinct mechanism of tumor immunity

AUTHOR CONTACT:
Jay A. Berzofsky
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Phone: 301.496.6874; Fax: 301.480.0681; E-mail: berzofsk@helix.nih.gov.

Masaki Terabe
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Phone: 301.435.8349; Fax: 301.402.0549; E-mail: terabe@mail.nih.gov.

View this article at: http://www.jci.org/articles/view/42314?key=1e385deea396d3927571

VIROLOGY: Homing in on the virus-infected cells that cause a fatal B cell tumor

Multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL) are fatal tumors; current treatments prolong survival by a few years at best. These tumors arise from immune cells known as B cells and are caused by Kaposi sarcoma–associated herpesvirus (KSHV). Little is known about the identity of the B cell subtypes most susceptible to infection by KSHV, information that would provide invaluable insight into the development of these fatal tumors. In this context, Dean Kedes and colleagues, at the University of Virginia Health Systems, Charlottesville, have now identified a subset of human tonsillar cells as susceptible to infection with KSHV. Their data lead them to suggest that KSHV latently (silently) infects tonsillar IgM-lambda-expressing B cells, which then proliferate and acquire characteristics similar to those of the tumor cells in individuals with MCD.

TITLE: KSHV infects a subset of human tonsillar B cells, driving proliferation and plasmablast differentiation

AUTHOR CONTACT:
Dean H. Kedes
University of Virginia Health Systems, Charlottesville, Virginia, USA.
Phone: 434.243.2758; Fax: 434.982.1071; E-mail: kedes@virginia.edu.

View this article at: http://www.jci.org/articles/view/44185?key=890327e6501c6461d6e7

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[Press-News.org] JCI online early table of contents: Jan. 18, 2011