Advances in optogenetics
A team of Graz scientists led by Andreas Winkler from the Institute of Biochemistry at TU Graz, Austria, has set a milestone in the future development of novel red light- regulated optogenetic tools for targeted cell stimulation. For the first time ever, they were able to observe molecular principles of sensor-effector coupling in the full-length structure of a red-light responsive protein and describe detailed mechanisms of signal transmission over long distances at a molecular level. The results of the research have been published in the open access journal, Science Advances. The research contributes to better understanding the modularity of naturally occurring protein domains and being able to develop new optogenetic tools. Diverse combinations of different sensor modules are found in nature, such as red-light sensors, blue-light sensors and pH sensors — sometimes with identical and sometimes different effectors. From this, the researchers conclude that there are molecular similarities in signal transduction and therefore that rational and completely arbitrary combinations of sensors and effectors which do not occur in nature are conceivable. Andreas Winkler says: “We are currently limited to naturally occurring systems to a great extent in the use of directly regulated enzymatic functionalities. The long-term aim is to generate new light-regulated systems which can overcome the limitations of nature and which would be of great interest for different applications in optogenetics.”
Ask the right question
The fractured political climate in the United States might be made worse by how we approach difficult problems, researchers have said in the journal Science. They suggest that rather than asking citizens “What do you want?”, questions should be asked in a deliberative frame: “What should we do?”
“Even this small shift in how we ask questions can have profound effects,” says Prof. Michael Neblo, lead author of the paper and associate professor of political science at the Ohio State University, U.S.
“Using this deliberative frame is not a cure-all for the problems of our political culture, but it can help nurture a healthier democracy.”
Prof. Neblo co-authored the Policy Forum article with colleagues from Ohio State, the University of California, Riverside, Northeastern University and Harvard University. Neblo and several colleagues have studied how this deliberative approach can help promote democracy. But that kind of research — which actually includes recommendations on how to improve our democratic systems — have become rare in contemporary political science.
In the years after World War II, about 20% of all articles in political science’s flagship journal, the American Political Science Review, made policy recommendations. That figure is less than 1% today.
The first gene-edited meal?
In what Swedish plant scientist Stefan Jansson declares “may be” a historic event, he cultivated, grew, and ate a plant that had its genome edited with CRISPR-Cas9. CRISPR (Clustered regularly interspaced short palindromic repeats)-Cas9 is a complicated name for an easy, but targeted, way of changing the genes of an organism. The decisive discovery was published in 2012 by researchers at Umeå University, Sweden, and the “Swiss army knife of genetic engineering” has been predicted to change the world. With CRISPR-Cas9, researchers can either replace one of the billions of “letters” present in an organism’s genome (i.e. the entire gene pool consisting of DNA) or remove short segments, similar to when you edit a written text in a word processor. The technology is called “gene editing” or “genome editing”. Umeå University where Prof. Jansson studies about how trees know it’s autumn and how proteins allow plants to harvest light, released a note on September 5 about his meal. It was a pasta dish that included 300 grams of cabbage he grew from seeds that had been genetically modified with CRISPR-Cas9. The revolutionary technology vastly simplifies the editing of genes, and has triggered many debates about whether its plant products should be considered a genetically modified organism (GMO) and subject to regulation. As noted by Science Daily and other media outlets, Prof. Jansson enjoyed the lunch with Gustaf Klarin, host of a Radio Sweden gardening show, which broadcast it earlier this week (in Swedish). “To our delight — and to some extent to my surprise—the meal turned out really nice,” Prof. Jannson wrote in a blog entry on August 16, the actual day that history might have been made. “Both of us ate with great relish. Gustaf even thought the cabbage was the best tasting vegetable on the plate. And I agreed.” — Jon Cohen, ScienceMag
New evidence of human evolution
Two partial archaic human skulls, from the Lingjing site, Xuchang, central China, provide a new window into the biology and populations patterns of the immediate predecessors of modern humans in eastern Eurasia. Securely dated to about 100,000 years ago, the Xuchang fossils present a mosaic of features. With late archaic (and early modern) humans across the Old World, they share a large brain size and lightly built cranial vaults with modest brow ridges. With earlier (Middle Pleistocene) eastern Eurasian humans, they share a low and broad braincase, one that rounds onto the inferior skull. With western Eurasian Neandertals, they share two distinct features — the configuration of their semicircular canals and the detailed arrangement of the rear of the skull. “The biological nature of the immediate predecessors of modern humans in eastern Eurasia has been poorly known from the human fossil record,” says Erik Trinkaus, a corresponding author for the study and professor of anthropology at Washington University in St. Louis. “The discovery of these skulls of late archaic humans, from Xuchang, substantially increases our knowledge of these people.” More importantly, he noted: “The features of these fossils reinforce a pattern of regional population continuity in eastern Eurasia, combined with shared long-term trends in human biology and populational connections across Eurasia. They reinforce the unity and dynamic nature of human evolution leading up to modern human emergence.”
A progeria-on-a chip model
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic condition that causes premature and accelerated aging. Recently, researchers have been able to generate induced pluripotent stem cells from patients with HGPS to better understand the mechanisms of aging and look for new treatments. HGPS primarily affects vascular cells, which undergo biomechanical strains in blood vessels. However, the impact of these biomechanical strains on aging and vascular diseases has been challenging to study in the lab as most models fail to mimic the biomechanics that cells experience in the body. Using a new progeria-on-a-chip model, investigators from Brigham and Women’s Hospital, Boston, Massachusetts, U.S., led by João Ribas, PhD candidate, and Ali Khademhosseini, PhD, of the Biomaterials Innovation Research Center, have developed a way to recapitulate blood vessel dynamics to better understand vascular disease and aging.
The new organ-on-a-chip device consists of a top fluidic channel and underlying vacuum channel, which mimics, upon pressure, the mechanical stretching that cells experience within blood vessels. The team found that cells derived from HGPS donors but not from healthy donors showed an exacerbated response to biomechanical strain, with an increase in markers of inflammation, which are strongly associated with vascular disease and aging.
“Vascular diseases and aging are intimately linked yet rarely studied in an integrated approach,” the authors write. “Gaining a deeper understanding of the molecular pathways regulating inflammation during vascular aging might pave the way for new strategies to minimising cardiovascular risk with age.”