Clues to Mechanism of Lithium Action in Bipolar Disease

New research provides insights into how lithium works in the treatment of bipolar mood disorder, and may lay the groundwork for advances in the treatment of this disease. Scientists from Cardiff University, together with colleagues, have shown that lithium inhibits the enzyme inositol monophosphatase, and this leads to the inhibition of the production of PIP3, a molecule that is important in controlling brain cell signaling. Professor Adrian Harwood of Cardiff School of Biosciences, who led the research, said “We still cannot say definitively how lithium can help stabilize bipolar disorder. However, our research does suggest a possible pathway for its operation. By better understanding lithium, we can learn about the genetics of bipolar disorder and develop more potent and selective drugs. Further, altered PIP3 signalling is linked to other disorders, including epilepsy and autism, so this well established drug could be used to treat other conditions.” The research was published in Disease Models & Mechanisms. [Press release]

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DICER1 Mutations Implicated in Rare Childhood Cancer

Mutations in the microRNA processing enzyme DICER1 appear to the cause of the inherited form of a rare, aggressive childhood cancer called pleuropulmonary blastoma (PPB). “PPB is the first malignancy found to be directly associated with inherited DICER1 mutations, making the cancer an important model for understanding how mutations and loss of DICER1 function lead …

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Possible New Avenue for Huntington Disease Treatment

Increasing the levels of a key protein (RCAN1-1L) can, in vitro, rescue cells from the toxic effects of mutant huntingtin proteins that cause Huntington disease. “Our findings allow for the possibility that controlled over-expression of RCAN1-1L might in the future be a viable avenue for therapeutic intervention in Huntington disease patients,” said Kelvin J. A. …

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Novel Drug Targeted at Cancer Stem Cells Shows Promise in Pancreatic Cancer

The combination of a novel drug (tigatuzumab) directed against pancreatic cancer stem cells, and the drug (gemcitabine) currently used for the treatment of pancreatic cancer, has shown promising results in achieving tumor remission and preventing recurrence. Tigatuzumab is a humanized antibody directed against death receptor-5, which the researchers showed is overexpressed in pancreatic cancer stem …

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Nine New X-Chromosome Genes Associated with Learning Disabilities

Researchers have identified nine new genes on the X-chromosome that, when mutated, are associated with learning disabilities. “We sequenced 720 out of the approximately 800 known genes on the X chromosome in more than 200 families affected by X-linked learning disabilities,” explained Professor Michael Stratton, from the Wellcome Trust Sanger Institute. “This is the largest …

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Synthesis of Anti-Leukemia Compounds from South Pacific Sponge

Scientists at the Scripps Research Institute have succeeded in synthesizing kapakahines, compounds with anti-leukemia potential that are normally produced in vanishingly small quantities by the South Pacific tube-type sponge Cripbrochalina olemda. With the synthetic process in hand, it will be possible, for the first time, to produce kapakahines in quantities sufficient for thorough study of …

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Origins of Deadly Prostate Cancer Traced to Single Aberrant Cell

The origins of metastatic prostate cancer cells can be traced to a single original cancer cell in individuals. This is the conclusion of a 14-year autopsy-based study of copy number variation in the cells of prostate cancer victims. The study was carried out by researchers at Johns Hopkins and collaborating institutions. The findings call into …

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Possible Cell Adhesion Role for Normal Prion Protein

Scientist have reported the creation of a strong loss-of-function phenotype for the normal prion protein (PrP) in zebrafish embryos. This phenotype is characterized by the loss of embryonic cell adhesion and arrested gastrulation. The results of additional experiments indicate that the normal prion protein (1) mediates Ca+2-independent homophilic cell adhesion and signaling; and (2) modulates …

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Inbreeding Role in Extinction of the Spanish Habsburg Dynasty

Statistical genetic evidence supports the history-based theory that inbreeding may have played a role in the extinction of the Spanish Habsburg dynasty (1516-1700). This is the conclusion of research reported in an April 15 article in PLoS. The Spanish Habsburg dynasty was characterized by the frequent marrige of close relatives, in such a way that uncle-niece, first cousin, and other consanguineous unions were common. The dynasty ended with the childless death of the physically and mentally disabled Charles II at the age of 39. [PLoS article]

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Molecular Switch Inhibition May Aid Treatment of Deadly Brain Cancers

Inhibition of the expression of a gene called NHERF-1 may be useful in the treatment of deadly brain cancers in the class glioblastoma multiforme (GBM), according to findings published by researchers at the Translational Genomics Research Institute (TGen) and Barrow Neurological Institute in the April issue of Neoplasia. “Our findings suggest a novel mechanism defining NHERF-1 as a ‘molecular switch’ that regulates the GBM tumor cell’s ability to migrate or divide,” said Dr. Kerri Kislin, the lead author of the study. The findings will be presented during the AACR annual meeting April 18-22. [Press release]

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