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There is accumulating evidence from bioinformatic studies that hepatitis C virus (HCV) possesses extensive RNA secondary structure in the core and NS5B-encoding regions of the genome. Recent functional studies have defined one such stem-loop structure in the NS5B region as an essential cis-acting replication element (CRE). A program was developed (STRUCTUR_DIST) that analyses multiple rna-folding patterns predicted by mfold to determine the evolutionary conservation of predicted stem-loop structures and, by a new method, to analyse frequencies of covariant sites in predicted RNA folding between HCV genotypes. These novel bioinformatic methods have been combined with enzymic mapping of RNA transcripts from the core and NS5B regions to precisely delineate the RNA structures that are present in these genomic regions. Together, these methods predict the existence of multiple, often juxtaposed stem-loops that are found in all HCV genotypes throughout both regions, as well as several strikingly conserved single-stranded regions, one of which coincides with a region of the genome to which ribosomal access is required for translation initiation. Despite the existence of marked sequence conservation between genotypes in the HCV CRE and single-stranded regions, there was no evidence for comparable suppression of variability at either synonymous or non-synonymous sites in the other predicted stem-loop structures. The configuration and genetic variability of many of these other NS5B and core structures is perhaps more consistent with their involvement in genome-scale ordered RNA structure, a structural configuration of the genomes of many positive-stranded RNA viruses that is associated with host persistence.

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Discrete RNA secondary and higher-order structures, typically local in extent, play a fundamental role in RNA virus replication. Using new bioinformatics analysis methods, we have identified genome-scale ordered RNA structure (GORS) in many genera and families of positive-strand animal and plant RNA viruses. There was remarkably variability between genera that possess this characteristic; for example, hepaciviruses in the family Flaviviridae show evidence for extensive internal base-pairing throughout their coding sequences that was absent in both the related pestivirus and flavivirus genera. Similar genus-associated variability was observed in the Picornaviridae, the Caliciviridae, and many plant virus families. The similarity in replication strategies between genera in each of these families rules out a role for GORS in a fundamentally conserved aspect of this aspect of the virus life cycle. However, in the Picornaviridae, Flaviviridae, and Caliciviridae, the existence of GORS correlated strongly with the ability of each genus to persist in their natural hosts. This raises the intriguing possibility of a role for GORS in the modulation of innate intracellular defense mechanisms (and secondarily, the acquired immune system) triggered by double-stranded RNA, analogous in function to the expression of structured RNA transcripts by large DNA viruses. Irrespective of function, the observed evolutionary conservation of GORS in many viruses imposes a considerable constraint on genome plasticity and the consequent narrowing of sequence space in which neutral drift can occur. These findings potentially reconcile the rapid evolution of RNA viruses over short periods with the documented examples of extreme conservatism evident from their intimate coevolution with their hosts.

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Frustrating isn't it?

Everybody told you social media is oh-so-important for generating traffic, so you focused so much of your time and effort building a following on Facebook, Twitter, Pinterest, or whatever the flavor of the month is today.

But every time you publish one of your blog posts, these sources don't seem to drive all that much traffic. Only a small percentage of the following you've built seems to click-through to your site.

Well, what if I told you about a social media platform that not only generates mass traffic, but you don´t even need many followers to benefit from it.

If you're disappointed with your results from traditional social media, you should try Flipboard.

Flipboard is an app and website that allows you to curate content in the forms of an online magazine. (Few people know it also has great potential as a source of traffic to your website. But more on that later. )

The reasons Flipboard is preferable to traditional social media are simple.

When you sign up for Flipboard, it first presents you with a big list of topics. You select what you're interested in, and when you're done, Flipboard will create an online magazine with cover stories from all the topics you selected.

These cover stories are articles selected by other users.

You can personally add articles to your Flipboard as well.

Imagine you find an article on copywriting that you’d like to read, but you don’t have time right at that moment. You might then add it to your Flipboard (also known as “flipping”), and later, when you do have some time, you can read it (and other articles you’ve flipped) at your leisure.

Flipboard's format differs from other content curation sites you find on the web. Instead of presenting the curated content on lists like on StumbleUpon or on boards like on Pinterest, Flipboard enables its users to have a real journalistic feel by collecting users' content into a magazine-style format.

So you must be wondering, how can this help you get traffic?

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Falmouth Housing Trust, Inc. is a 501(c)3 nonprofit organization.

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