NEWs FROM EMBO scIENTIFIc pUBlIcATIONs
Fragile X and Down syndromes share signalling pathway for intellectual disability
Intellectual disability due to Fragile X and Down syndromes involves similar molecular pathways. The two disorders share disturbances in the molecular events that regu-
late the way nerve cells develop dendritic spines, the small exten- sions found on the surface of nerve cells that are crucial for communi- cation in the brain.
“We have shown for the first time that some of the proteins altered in Fragile X and Down syndromes are common molecular triggers
of intellectual disability in both disorders,” said Kyung-Tai Min, one of the lead authors of the study and a professor at Indiana University and the Ulsan National Institute of Science and Technology in Korea.
“Specifically, two proteins interact with each other in a way that limits the formation of spines or protru- sions on the surface of dendrites.” He added: “These outgrowths of the cell are essential for the forma- tion of new contacts with other nerve cells and for the success-
ful transmission of nerve signals. When the spines are impaired, information transfer is impeded and mental retardation takes hold.”
DSCR1 interacts with FMRP and is required for spine morphogenesis and local protein synthesis
Wei Wang, John Z. Zhu, Karen T. Chang, Kyung-Tai Min
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No evidence for 30-nm chromatin fibres in the mouse genome
Scientists in Canada and the United States have used three-dimensional imaging techniques to settle a long-standing debate about how DNA and structural proteins are packaged into chromatin fibres. The researchers reveal that the mouse genome consists of 10-nm chromatin fibres but did not find evidence for the wider 30-nm fibres that were previously thought to be important components of the DNA architecture.
“DNA is an exceptionally long molecule that can reach several metres in length. This means it needs to be packaged into a highly compact state to fit within the limit- ed space of the cell nucleus,” said David Bazett-Jones, Senior Scientist at the Hospital for Sick Children, Toronto, and the Professor at the University of Toronto, Canada. “For the past few decades, scientists have favoured structural models for chromatin organization where DNA is first wrapped around proteins
in nucleosomes. In one possible model, the strand of repeating nucleosomes is wrapped further into a higher-order thick 30-nm fibre. In a second model, the 30-nm fibre is not required to compact the DNA. Differences between these models have implications for the way the cell regulates the transcrip- tion of genes.”
Open and closed domains in the mouse genome are configured as 10 nm chroma- tin fibres
Eden Fussner, Mike Strauss, Ugljesa Djuric, Ren Li, Kashif Ahmed, Michael Hart, James Ellis, and David P. Bazett-Jones
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Computational analysis identifies drugs to treat drug-resistant breast cancer
Researchers have used computa- tional analysis to identify a new Achilles heel for the treatment of drug-resistant breast cancer. The results reveal that the disruption of glucose metabolism is an effective therapeutic strategy for the treat- ment of tumours that have acquired resistance to front-line cancer drugs such as Lapatinib.
“The growth and survival of cancer cells can often be impaired by treatment with drugs that interfere with the actions of one or more oncogenes,” said Prahlad Ram, the senior author of the study
and Professor at the University of Texas MD Anderson Cancer Center, Houston, Texas. “However, the clinical benefits to patients are often short lived due to acquired drug resistance. Finding alternative intervention points or so-called new addictions for cancer cells is of critical importance for designing novel therapeutic strategies against tumours. Our results reveal specific new targets for drug intervention in the metabolic pathways of cancer cells and identify existing drugs that can be used to treat drug- resistant cancer.”
The glucose-deprivation response network counteracts EGFR signalling in lapatinib resistant cells
Kakajan Komurov, Jen-Te Tseng,
Melissa Muller, Elena G Seviour,
Tyler J Moss, Lifeng Yang, Deepak Nagrath, Prahlad T Ram
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Scientists reveal how natural antibiotic kills tuberculosis bacterium
A natural product secreted by a soil bacterium shows promise as a new drug to treat tuberculosis. A team of scientists working in Switzerland has shown how pyridomycin, a natural antibiotic produced by
the bacterium Dactylosporangium fulvum, works. This promising drug candidate is active against many of the drug-resistant types of the tuberculosis bacterium that no longer respond to treatment with the front-line drug isoniazid.
“Nature and evolution have equipped some bacteria with potent defense mechanisms to protect them against other bugs that share their habitat. Screening natural products generated by these organ- isms is therefore a powerful way
to find possible new drugs to fight infectious diseases,” said Stewart Cole, lead author of the study, EMBO Member and a professor at the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland.
“Using this approach we have shown that nature’s antibiotic pyri- domycin is a very selective killer
of Mycobacterium tuberculosis, the bacterium responsible for tuber- culosis in humans. It is also active against mycobacteria that have developed resistance to front-line drug treatments such as isoniazid.”
Towards a new tuberculosis drug: Pyridomycin – Nature’s isoniazid
Ruben C Hartkoorn, Claudia Sala, João Neres, Florence Pojer, Sophie J. Magnet, Raju Mukherjee, Swapna Uplekar, Stefanie Boy-Röttger, Karl-Heinz Altmann, Stewart T. Cole
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