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Sunday, December 16, 2018

Citybblog Feature MPC News

Cityblog User: Most Visited Cities in the World

Cityblog User: Andhra Pradesh

Cityblog Feature: PJ of the Day

Dronacharya ne Ekalavya ka angutha liya
Arjun Ko Dhanurvidya ki poori aur acchi shiksha meeli
Lekin Karan us shiksha se vanchit rehkar bhi utnehi acche dhanurdhar bane
To Vastav mein hero Kaun tha

Cityblog Special: Unique Basketball

Cityblog Feature: Fitness Tips from Fitcon

Half of America hasn't recovered from the recession

A decade after the financial crisis, the U.S. economy seems to be firing on all cylinders, with unemployment at a 50-year low and growth hitting its stride. But a deeper look reveals a more troubling picture: Between 2012 and 2015 -- a period when the recovery seemed to be gaining speed -- nearly half of all counties nationwide saw flat or declining growth, according to new government data. 
More broadly, the Commerce Department figures highlight a stark and worrisome reality: While a handful of places around the U.S. are thriving, most regions are barely trudging ahead. And that trend is creating a widening geographic gap between a relatively few prosperous areas, mostly urban oases, and the desert of stagnation that lies beyond.  
"For many communities, what you've got is a lost decade of economic growth," said John Lettieri, CEO of the Economic Innovation Group, a bipartisan think tank, adding that "the topline economy doesn't match the local experiences." 

Cityblog Special" Festival of Lights

People view illuminations at the annual Festival of Light at the Elizabethan Longleat House near Frome in Wiltshire, England, on December 12, 2018.

Saturday, December 15, 2018

Scientists crack the CRISPR code for precise human genome editing

Scientists at the Francis Crick Institute have discovered a set of simple rules that determine the precision of CRISPR/Cas9 genome editing in human cells. These rules, published in Molecular Cell, could help to improve the efficiency and safety of genome editing in both the lab and the clinic.

Despite the wide use of the CRISPR system, rational application of the technology has been hindered by the assumption that the outcome of genome editing is unpredictable, resulting in random deletions or insertions of DNA regions at the target site.

Before CRISPR can be safely applied in the clinic, scientists need to make sure that they can reliably predict precisely how DNA will be modified.

"Until now, editing genes with CRISPR has involved a lot of guesswork, frustration and trial and error," says Crick group leader Paola Scaffidi, who led the study. "The effects of CRISPR were thought to be unpredictable and seemingly random, but by analysing hundreds of edits we were shocked to find that there are actually simple, predictable patterns behind it all. This will fundamentally change the way we use CRISPR, allowing us to study gene function with greater precision and significantly accelerating our science."

By examining the effects of CRISPR genome editing at 1491 target sites across 450 genes in human cells, the team have discovered that the outcomes can be predicted based on simple rules. These rules mainly depend on one genetic 'letter' occupying a particular position in the region recognized by the 'guide RNA' to direct the molecular scissors, Cas9 .

Guide RNAs are synthetic molecules made up of around 20 genetic letters (A,T,C,G), designed to bind to a specific section of DNA in the target gene. Each genetic letter has a complementary partner—A binds to T and C binds to G—which stick together a bit like Velcro. The guide RNA is like the 'hook' side of Velcro, designed to stick to the 'loop' side on the target gene.

Guided by the RNA molecule, the Cas-9 enzyme scans along the genome until it finds the region of interest. When the RNA guide matches the correct DNA sequence, it sticks like Velcro and Cas9 cuts through the DNA. The DNA is broken three letters from the end of the target sequence, and bits of genetic code are then inserted or deleted, seemingly haphazardly, when the cell attempts to repair the break.

In this study, the researchers found that the outcome of a particular gene edit depends on the fourth letter from the end of the RNA guide, adjacent to the cutting site. The team discovered that if this letter is an A or a T, there will be a very precise genetic insertion; a C will lead to a relatively precise deletion and a G will lead to many imprecise deletions. Thus, simply avoiding sites containing a G makes genome editing much more predictable.

"We were amazed to discover that the rules that determine the outcome of CRISPR human genome editing are so simple," says Dr. Anob Chakrabarti, Wellcome Trust clinical Ph.D. fellow in the Crick's Bioinformatics and Computational Biology lab and joint-first author of the study. "By bearing these rules in mind when designing our guide RNAs, we can maximise the chances of getting the desired outcome of a specific gene edit—which is particularly important in a clinical context."

The team also discovered that how 'open' or 'closed' the target DNA is also affects the outcome of gene editing. Adding compounds that force DNA to open up—allowing Cas9 to scan the genome—led to more efficient editing, which could help when modifications need to be introduced in particularly closed genes.

"The good news is that regardless of the tissue of origin—which influences the degree of DNA 'openness' at specific genes—target regions containing an A or T at the key position show common editing," says Paola. "This means that, if we carefully select the target DNA, we can be pretty confident that we'll see the same effect in different tissues."

Josep Monserrat, Crick Ph.D. student in the Cancer Epigenetics lab and joint-first author of the study, says: "We hadn't previously appreciated the significance of DNA openness in determining the efficiency of CRISPR genome editing. This could be another factor to consider when aiming to edit a gene in a specific way. We are excited to observe that distinct cell types share common editing at precise target regions, and hope translation of our findings will be beneficial across disciplines."


Cityblog Special: FO Nirmal Jit Singh Sekhon

Cityblog Feature: PJ of the day

Why was Astronaut's Wife Unhappy?

Cityblog Special: Future of Magic