{"id":396,"date":"2008-03-27T13:25:27","date_gmt":"2008-03-27T13:25:27","guid":{"rendered":"https:\/\/blogs.nature.com\/spoonful\/2008\/03\/strong-nature.html"},"modified":"2008-03-27T13:25:27","modified_gmt":"2008-03-27T13:25:27","slug":"strong_nature","status":"publish","type":"post","link":"https:\/\/blogs.nature.com\/spoonful\/2008\/03\/strong_nature.html","title":{"rendered":"Strong Nature"},"content":{"rendered":"

I found the past two online installments of Nature<\/em> to be particularly strong.<\/p>\n

Sunday’s issue had two papers showing that activation of the aryl hydrocarbon receptor (AHR<\/span>) — a ligand-dependent transcription factor that mediates the action of environmental toxins such as dioxin — plays a role in the pathophysiology of EAE<\/span>, the commonly used animal model of multiple sclerosis.<\/p>\n

Marc Veldhoen et al.<\/em><\/a> and Francisco Quintana et al.<\/em><\/a> found that AHR<\/span> exacerbated EAE<\/span> by promoting the differentiation of Th17 cells and the production of IL-22. Remarkably, Quintana and his colleagues went on to show that the effect of AHR<\/span> depended on the agonist they used; whereas one agonist promoted EAE<\/span>, a different agonist suppressed the pathology by inducing regulatory T cells. The authors don’t go too far downstream to nail down the transcriptional pathways that are responsible and account for the dual effect of AHR<\/span> (which is in and of itself not unprecedented<\/a>), but the possibility that environmental toxins might use this receptor to modify the course of multiple sclerosis in people is very interesting.<\/p>\n

Then, on today’s edition of the journal, there are two RNA<\/span>-related papers that are also very interesting. The first one is a proof-of-principle study by Joacim Elm\u00e9n et al.<\/em><\/a>, showing that it is possible to silence microRNAs in non-human primates. Although therapeutic effects of blocking microRNAs in rodents have been published, there has been scepticism about translating the approach to the clinic. Elm\u00e9n and his colleagues now show that it is possible to silence a liver microRNA in the green monkey by delivering a locked-nucleic-acid-modified “antimiR”. Moreover, this silencing approach had a functional readout — decreased plasma cholesterol — and no obvious toxicity. This is a reassuring finding for those interested in targeting microRNAs in humans with therapeutic purposes.<\/p>\n

The second RNA<\/span>-related paper reports a somewhat unexpected finding. There are reports that you can use siRNA to target proangiogenic molecules like VEGF<\/span> or its receptor, and block pathological angiogenesis in patients with neovascularization linked to age-related macular degeneration. Now, Mark Kleinman and his colleagues<\/a> show that it doesn’t quite matter what molecule you target because a large number of siRNAs (even if some that target non-genomic sequences or antiangiogenic genes) have the same antiangiogenic effect. As long as the siRNA is 21-nucleotides or longer, it will exert an anti-angiogenic effect mediated by the TLR3 signaling cascade. This “class effect” implies that generic siRNAs might be therapeutic agents, and that siRNAs might have unanticipated actions on the vascular and immune systems.<\/p>\n","protected":false},"excerpt":{"rendered":"

I found the past two online installments of Nature to be particularly strong.  Read more<\/a> Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":162,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[],"class_list":["post-396","post","type-post","status-publish","format-standard","hentry","category-journal-club"],"_links":{"self":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/posts\/396","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/users\/162"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/comments?post=396"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/posts\/396\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/media?parent=396"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/categories?post=396"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nature.com\/spoonful\/wp-json\/wp\/v2\/tags?post=396"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}