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How are we warm-blooded? A picture of CRISPR/Cas and fragile X advance

April 2015 Cell Press spotlight: A media tip Sheet

Cell Press

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IMAGE: This is a three-dimensional crystal structure of CRISPR/Cas capturing RNA. view more

Credit: Osawa et al./Molecular Cell 2015

CRISPR/Cas system in three dimensions

The CRISPR/Cas system has gained a reputation as one of the most exciting biomedical tools of our time. These interacting pieces of genetic material can target and make precise cuts to DNA or RNA, bringing scientists' hopes of therapeutic genetic engineering closer to reality. In nature, CRISPR/Cas is used by bacteria as an elementary immune system. They capture invading pieces of genetic information (e.g., from viruses) and chop it up. For the first time, scientists from the National Institute of Advanced Industrial Science and Technology in Japan have generated a three-dimensional "crystal structure" of the CRISPR/Cas system in action. The researchers, publishing in Molecular Cell, hope this detailed understanding of the CRISPR/Cas structure can inform how the machinery can be used.

Osawa et al.: "Crystal Structure of the CRISPR-Cas RNA Silencing Cmr Complex Bound to a Target Analog." Molecular Cell. (April 23, 2015) http://dx.doi.org/10.1016/j.molcel.2015.03.018

Why do arteries and veins run parallel to one another?

Any student of mammalian anatomy and physiology knows that arteries carry blood away from the heart and veins carry blood toward the heart. Like two sides of a highway, these blood vessels are kept relatively adjacent and parallel to one another. Without this alignment, mammals may not be able to regulate their body temperature, a key feature of being warm-blooded. In Developmental Cell, a collaborative of Japanese and German researchers report that, in both cold and hot conditions, mice without aligned veins/arteries are unable to regulate their body temperature efficiently. The authors, who investigated the molecular mechanisms that control this alignment, believe that the vein/artery configuration and thermoregulation connection might be a recent evolutionary adaptation, as "lower" animals such as fish and reptiles both lack parallel veins and arteries and are cold-blooded. The vessel alignment is accomplished via an elegant interplay between the vessels--arteries secrete a factor to directly attract veins - and neutrophils, which physically clear the way for venous migration by remodeling the extracellular matrix surrounding the vessels.

Kidoya et al.: "APJ Regulates Parallel Alignment of Arteries and Veins in the Skin" Developmental Cell. (April 23, 2015) http://dx.doi.org/10.1016/j.devcel.2015.02.024

New treatment strategy for fragile X syndrome

Researchers are searching for new treatment options after recently concluded clinical trials for fragile X syndrome, an inherited intellectual disability and autism spectrum disorder, did not show the expected improvements in core behavioral phenotypes. The trials, which tested a drug that interfered with how the neurotransmitter glutamate acts in the brain, didn't disprove the connection between glutamate and fragile X, but they emphasized the need for further development of alternative or additional treatment strategies. In two connected Cell Reports papers, an Emory-University-led research team shows how genetically altering a downstream influencer on glutamate receptors helped to reverse some symptoms of mice born with a fragile-X-like disorder. The scientists next plan to test whether a drug could mimic this effect in the mouse model.

Gross et al.: "Increased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome" Cell Reports. (April 23, 2015) http://dx.doi.org/10.1016/j.celrep.2015.03.060

Gross et al.: "Selective Role of the Catalytic PI3K Subunit p110? in Impaired Higher Order Cognition in Fragile X Syndrome" Cell Reports. (April 23, 2015) http://dx.doi.org/10.1016/j.celrep.2015.03.065

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