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HomeCirculationVol. 141, No. 4From the Literature Free AccessNewsPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessNewsPDF/EPUBFrom the Literature Tracy Hampton, PhD Tracy HamptonTracy Hampton Search for more papers by this author Originally published27 Jan 2020https://doi.org/10.1161/CIRCULATIONAHA.119.045068Circulation. 2020;141:329–330High Salt Intake Linked to Cognitive Impairment in MiceResearchers have discovered a causal link between a salt-rich diet and cognitive dysfunction in mice that involves phosphorylation of tau, a hallmark of Alzheimer disease.As described in a study published in Nature, the cognitive effects of elevated dietary salt (8–16 times higher than a normal mouse diet) were associated with decreased cerebral blood flow, as well as suppressed production of nitric oxide by cerebral endothelial cells. The effect was independent of hypertension. This nitric oxide deficit resulted in activation of the cyclin-dependent kinase that is involved in tau phosphorylation.These effects were prevented by restoring endothelial nitric oxide production. The team also reported that salt-induced cognitive impairment was not observed in mice lacking tau or in mice treated with anti-tau antibodies, despite persistently decreased cerebral blood flow and neurovascular dysfunction.Although the high-salt diet fed to the mice exceeds the highest reported levels of salt consumption in humans (3–5 times the recommended level of 4–5 grams per day), the findings suggest that avoiding excessive salt intake may help to slow or prevent dementia.“Our finding that excessive dietary salt leads to accumulation of the Alzheimer’s protein tau provides a previously unrecognized link between vascular risk factors and Alzheimer pathology,” said senior author Dr Costantino Iadecola, of Weill Cornell Medicine. “The effect of salt on cognition is independent of the associated reduction in cerebral blood flow, but is related to tau, and endothelial nitric oxide is critical to maintain the homeostasis of tau.”Faraco G et al. Dietary salt promotes cognitive impairment through tau phosphorylation. Nature. 2019;574:686–690. doi: 10.1038/s41586-019-1688-zDownload figureDownload PowerPointResearchers have uncovered a causal link between elevated salt intake and cognitive impairment in mice.New Search-and-Replace Genome Editing Tool Avoids DNA BreaksA new genome editing method called prime editing draws on advances of CRIPSR-Cas9 technology but avoids double-stranded DNA breaks, which can lead to undesired outcomes. In principle, the technique could correct an estimated 89% of known human genetic variants associated with diseases.Prime editors consist of an engineered protein, a fusion of a disabled Cas9 enzyme and a reverse transcriptase, and an engineered RNA that together orchestrate a series of DNA targeting, DNA writing, and DNA repair steps that result in an edit.The prime editor protein cannot make double-stranded cuts in DNA but retains Cas9’s ability to bind a target DNA sequence in a programmable manner. The engineered RNA is a prime editor guide RNA that both specifies the target DNA site and also encodes the desired edit. The reverse transcriptase component of the prime editor protein directly copies the part of the prime editor guide RNA that encodes the edited DNA sequence into the target DNA site, resulting in a new flap of DNA that contains the edit.The prime editor system then helps the cell incorporate this edited flap, replacing the original DNA sequence on both strands of the DNA double helix. The result is a permanent edit that has been copied from the information encoded in the prime editor guide RNA.In a study published in Nature, the researchers performed more than 175 edits in various types of human cells, and they successfully corrected the primary genetic causes of sickle cell disease and Tay Sachs disease. The technique was more efficient and had lower off-target editing than traditional Cas9 editing.“In many respects, this first report of prime editing is the beginning, rather than the end, of a longstanding aspiration to be able to make any DNA change in any position of a living cell or organism, including human patients with genetic diseases,” said senior author Dr David Liu, of the Broad Institute of Harvard and MIT. “Much more work is needed to fully realize this goal, including additional studies to characterize potential effects of prime editors in cells, to maximize their compatibility with additional cell types, and to interface viral and non-viral delivery methods to enable prime editing in live animals.”Anzalone AV et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019 Oct 21. doi: 10.1038/s41586-019-1711-4Health and Environmental Impacts of FoodA new analysis describes how consuming 15 different food groups is associated with 5 health outcomes and 5 aspects of environmental degradation. By combining and analyzing results from previous analyses, investigators concluded that the same dietary choices that would lower incidences of noncommunicable diseases would also improve environmental sustainability.In the analysis published in the Proceedings of the National Academy of Sciences, nuts, minimally processed whole grains, fruits, vegetables, legumes, olive oil, and fish were associated with reduced mortality and reduced risk for 1 or more diseases including heart disease, diabetes mellitus, stroke, and colorectal cancer. Foods associated with a larger reduction in risk for 1 health outcome were often associated with larger reductions in risk for other health outcomes.Likewise, foods with lower impacts on 1 metric of environmental harm—greenhouse gas emissions, land use, scarcity-weighted water use, acidification, and eutrophication (2 forms of nutrient pollution)—tended to have lower impacts on others.In addition, of the foods associated with improved health, all except fish had among the lowest environmental impacts, and fish had markedly lower impacts than red meats and processed meats.Foods associated with the largest negative environmental impacts— unprocessed and processed red meat—were associated with the largest increases in disease risk. Sugar-sweetened beverages were associated with increased disease risk but low environmental harm.“Global diets have been shifting toward greater consumption of foods associated with increased disease risk or higher environmental impacts and are projected to lead to rapid increases in diet-related diseases and environmental degradation,” the authors wrote. “Reversing this trend in the regions in which it has occurred and instead increasing consumption of whole grain cereals, fruits, vegetables, nuts, legumes, fish, and olive oil and other vegetable oils high in unsaturated fats—foods that are consistently associated with decreased disease risk and low environmental impacts—would have multiple health and environmental benefits globally.”Clark MA et al. Multiple health and environmental impacts of foods. Proc Natl Acad Sci U S A. 2019;116:23357–23362. doi: 10.1073/pnas.1906908116Footnoteshttps://www.ahajournals.org/journal/circ Previous Back to top Next FiguresReferencesRelatedDetails January 28, 2020Vol 141, Issue 4 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.119.045068PMID: 31986092 Originally publishedJanuary 27, 2020 PDF download Advertisement