Although genome-wide association studies (GWAS) have identified more than 100 colorectal cancer risk loci, most of the biological mechanisms associated with these loci remain unclear. Here we first performed a comprehensive expression quantitative trait loci analysis in colorectal cancer tissues adjusted for multiple confounders to test the determinants of germline variants in established GWAS susceptibility loci on mRNA and long noncoding RNA (lncRNA) expression. Combining integrative functional genomic/epigenomic analyses and a large-scale population study consisting of 6,024 cases and 10,022 controls, we then prioritized rs174575 with a C>G change as a potential causal candidate for colorectal cancer at 11q12.2, as its G allele was associated with an increased risk of colorectal cancer (OR = 1.26; 95% confidence interval = 1.17–1.36; P = 2.57 × 10–9). rs174575 acted as an allele-specific enhancer to distally facilitate expression of both FADS2 and lncRNA AP002754.2 via long-range enhancer–promoter interaction loops, which were mediated by E2F1. AP002754.2 further activated a transcriptional activator that upregulated FADS2 expression. FADS2, in turn, was overexpressed in colorectal cancer tumor tissues and functioned as a potential oncogene that facilitated colorectal cancer cell proliferation and xenograft growth in vitro and in vivo by increasing the metabolism of PGE2, an oncogenic molecule involved in colorectal cancer tumorigenesis. Our findings represent a novel mechanism by which a noncoding variant can facilitate long-range genome interactions to modulate the expression of multiple genes including not only mRNA, but also lncRNA, which provides new insights into the understanding of colorectal cancer etiology.Significance:This study provides an oncogenic regulatory circuit among several oncogenes including E2F1, FADS2, and AP002754.2 underlying the association of rs174575 with colorectal cancer risk, which is driven by long-range enhancer–promoter interaction loops.Graphical Abstract:http://cancerres.aacrjournals.org/content/canres/80/9/1804/F1.large.jpg.

BACKGROUND AND PURPOSE:

Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results.

BACKGROUND AND PURPOSE:

The increased severity of white matter disease is associated with worse outcomes and an increased rate of intracerebral hemorrhage in patients with ischemic stroke undergoing thrombolytic treatment. However, whether white matter disease is associated with outcomes in patients undergoing endovascular treatment remains unclear.

Bearing in mind that maintaining a united front against the virus can bode well for the country.

Home moving is surely a hassle. Luckily, a little preparation work can mean the difference between a minor headache and an all-out life takeover.

Along with the recovery of market, property investment also rebounds with new trends. Here are three new trends of property investment that become more and more popular in 2015.

Ramadan 2020 Today Sehri & Iftar Time Table : जानिए रमजान में सहरी और इफ्तार का समय

Ramadan 2020 Today Sehri & Iftar Time Table : जानिए रमजान में सहरी और इफ्तार का समय

Ramadan 2020 Today Sehri & Iftar Time Table : जानिए रमजान में सहरी और इफ्तार का समय

Ramadan 2020 Today Sehri & Iftar Time Table : जानिए रमजान में सहरी और इफ्तार का समय

Ramadan 2020 Today Sehri & Iftar Time Table : जानिए रमजान में सहरी और इफ्तार का समय

An AI search engine takes one-tenth of a second to search more than 2 billion satellite images, identifying natural or built features that look alike, such as forests or military bases

Adrian Tchaikovsky's latest novel The Doors of Eden rewrites Earth's evolutionary history, with highlights including fish that upload their minds to supercomputers and cats that rule over primates

A 3D printed grate can be used to make a smart window that blocks heat from sunlight out in the summer while letting it through in the winter, conserving energy

In a new photography book, the home computer revolution of the 1970s, 1980s and 1990s is told through nostalgic industrial-design images

It does make several enormous assumptions about the future that now seem perilously flaky.

Alison Roman’s latest comments about Marie Kondo have not sparked joy.

In an interview with The New Consumer about her increased popularity and the avenues she might pursue to capitalize on it, the popular food columnist discussed her hesitance to put her name on a product line—citing the Japanese organization maven and Chrissy Teigen as examples of what she did not foresee in her own future.

“I have a collaboration coming out with [the cookware startup] Material, a capsule collection,” Roman said. “It’s limited edition, a few tools that I designed that are based on tools that I use that aren’t in production anywhere—vintage spoons and very specific things that are one-offs that I found at antique markets that they have made for me.”

Read more at The Daily Beast.

Huge constellations of satellites like SpaceX’s Starlink could make ground-based astronomy impossible, and we’re running out of time to deal with the problem

The first US woman to spacewalk flew on three shuttle missions and says nothing beats space flight – but her proudest achievement is helping to repair the Hubble Space Telescope

New images reveal threads of ultra-hot gas woven throughout the sun's corona, in the most detailed look at previously unseen parts of the atmosphere of our closest star

NASA has awarded $967 million to three space flight companies – Blue Origin, Dynetics and SpaceX – to build lunar landers that will be part of the Artemis programme to send humans to the moon by 2024

Your weekly selection of awesome robot videos

Your weekly selection of awesome robot videos

“I didn’t ‘sell out’ by making my dreams come true.”

The auction for the Port of Melbourne has come down to a three-way race with bidders lodging indicative bids.

New Pokemon Go Throwback challenges start today for the Johto region. Here's a recap of all field research tasks and rewards on offer for the next seven days.

It’s almost here! We play your…insightful E3 voicemails. Then we give our…questionable E3 predictions. Finally, we give you some E3 plushies just for you, our...

FFXIV gets chocobos. Theatrhythm gets Mana. Browsers get SaGa. Vita gets TitS. And you get a new RPGCast. Happy new year!

RPG Cast is back, if a little bit lighter. See what one plays when they have three weeks without work. See what happens when THQ...

Happy Holidays! We wrap up the final podcast of the year affirming it's OK for Anna Marie to play casual games, even if Chris disagrees. While Josh and Kelley are making New Year's resolutions, Chris also disagrees about what should be a brief story. We'll see everyone in 2019!

It's the final podcast of the decade! Alex, Anna Marie, Chris, Kelley and Peter end the year with a bang...and maybe a whimper too. News, your lists of top DS games, and what we're going to play to ring in the new year. See you in 2020!

It's Alice's first appearance of the decade! Ther crew is rounded out by Alex, Anna Marie, Chris, Kelley and Peter who are back to discuss your treasured memories of the last decade, as well as the news, reviews, and releases from the last few weeks. Wasn't there supposed to be a break from releases...?

Mutations in white blood cells can contribute to abnormal immune profile after hematopoietic stem cell transplantation.

Chris Hemsworth plays a super-tough mercenary on an all-guns-blazing mission to rescue a crime lord’s kidnapped son

Sadly, this has nothing to do with dentistry. Extraction is a made-for-Netflix action thriller from veterans of the Marvel Comic Universe – screenwriter Joe Russo, stunt-specialist-turned-director Sam Hargrave and star Chris Hemsworth. It’s based on the graphic novel Ciudad (which Russo co-authored), transferring the action from the Paraguayan city of Ciudad Del Este to Dhaka in Bangladesh.

Extraction is a little bit hokey and absurd, and the very end has an exasperating cop-out – but it has to be admitted that, in terms of pure action octane, Russo and Hargrave bring the noise, and there are quite a few long-distance “sniper” scenes in which people get taken out from miles away as the bullet travels through their skulls with a resonant thoonk.

A ridiculously titled film about a couple who stumble upon a stash of money is absurd and cliched but mostly entertaining

One of the most surprising reveals of last October’s unprecedented Netflix data dump was the astounding popularity of cheap psycho-thriller Secret Obsession. While the streamer proudly touted new films from Alfonso Cuarón, Paul Greengrass and the Coens in the same period, it was a no-star, dim-plotted slab of schlock that netted more viewers, with an estimated 40m households eager to find out just how secret that obsession really was. Modelled after a Lifetime TV movie (with a Lifetime TV director at the helm), it was an important victory for Netflix because it revealed a substantial audience for tiny-budgeted thrillers with generic titles, a bracket they could easily fill at little expense.

Related: The Half of It review – charming Netflix teen comedy takes on Cyrano

Jameela Jamil also came to Teigen and Kondo's defense, calling Roman "distasteful" and "cliche" for criticizing women of color for being successful in business.

Video games can fill the productivity and social void in this unusual time

Astronomers using NASA’s Neil Gehrels Swift Observatory have tracked water loss from 2I/Borisov, the first known interstellar comet to visit our Solar System, as it approached and rounded the Sun. Their findings were published in the Astrophysical Journal Letters. 2I/Borisov was detected on August 30, 2019 by Gennady Borisov, an astronomer at the Crimean Astrophysical [...]

Fresh cases of Ebola have been detected just days before the deadly epidemic in the eastern Democratic Republic of the Congo was to be declared over

The covid-19 pandemic has led to rushed guidelines for doctors making treatment decisions, and has encouraged more people to make advance decisions on CPR and ventilation