The Delivery Man Synopsis The Delivery Man is a comedy television series produced by ITV that premiered in April of 2015. The Delivery Man follows the story of Matthew (played by Darren Boyd – Spy), a police officer who decides to switch careers in his mid-thirties and becomes a midwife. The Delivery Man is currently […]

Other Space Synopsis Other Space is a Science Fiction comedy television series produced by Yahoo that premiered in April of 2015. Created by Paul Feig (Freaks and Geeks) Other Space is set in the early 22nd century and follows the story of the inexperienced crew aboard UMP Cruiser on a routine space exploratory mission. In […]

Peter Kay’s Car Share Synopsis Peter Kay’s Car Share is a situation comedy television series produced by BBC One that premiered in April of 2015. Peter Kay’s Car Share follows the story of John (played by Peter Kay), an assistant manager in a supermarket and his co-worker and promotions rep Kayleigh (played by Sian Gibson). […]

Meet the Smiths Synopsis Meet the Smiths is a scripted reality television series produced by TBS that premiered in April of 2015. Meet the Smiths follows the daily lives of Kenny Smith, an NBA analyst for TNT and his wife Gwendolyn Osborne-Smith, a model for The Price is Right. The couple has five children together […]

Arranged Synopsis Arranged is a reality television series produced by the FYI Network that premiered in April of 2015. Arranged follows the story of the three American couples who all come from different backgrounds, but their cultural traditions allow for arranged marriages. The series chronicles their lives in the lead up to the wedding and […]

Wayward Pines Synopsis Wayward Pines is a mystery thriller television series produced by Fox Network and set to premiere in May of 2015. Based on the book Pines written by Blake Crouch and produced by M. Night Shyamalan Wayward Pines follows the story of an FBI agent Ethan Bruke (played by Matt Dillon), who travels […]

Miles from Tomorrowland Synopsis Miles from Tomorrowland is an animated television series produced by the Disney Channel that premiered in February of 2015. Miles from Tomorrowland is an American animated TV series about the adventures of an inquisitive, if somewhat reckless boy named Miles who travels the universe with his family. Miles from Tomorrowland is […]

The Protectors (1972) Synopsis The Protectors (1972) was an action thriller television series produced by ITV that premiered in September of 1972. The Protectors (1972) was a British action thriller series created by Gerry Anderson (Thunderbirds) about an international group of rich troubleshooters. Contessa di Contini (played by Nyree Dawn Porter), Paul Buchet (played by […]

Wormwood Synopsis Wormwood was a children’s television series produced by Network Ten and ABC1 that premiered in October of 2007. Made as a joint Canadian-Australian production, Wormwood was a TV series about a quirky town where a group of kids investigated strange events. The series was based on the stories written by Paul Jennings. Wormwood […]

A Sharp Intake Of Breath Synopsis A Sharp Intake Of Breath was a situation comedy television series produced by ITV that premiered in February of 1978. Created by Ronnie Taylor A Sharp Intake Of Breath followed the story of Peter Barnes (played by David Jason – Only Fools And Horses), an ordinary man who made […]

The following article, 77-Yr-Old MI Barber Defies Gov Whitmer’s Shutdown Order: ”I don’t need another mother” Shop Will Stay Open Until “Jesus walks in or until they arrest me” [VIDEO], was first published on 100PercentFedUp.com.

Emergency orders that “non-essential businesses” remain closed during the Covid-19 crisis have devastated small business owners across America. A wave of business owners across the nation are defying executive orders by their governors and opening their businesses anyhow. Yesterday, we reported about a small business owner in the state of Michigan, where Governor Gretchen Whitmer […]

Continue reading: 77-Yr-Old MI Barber Defies Gov Whitmer’s Shutdown Order: ”I don’t need another mother” Shop Will Stay Open Until “Jesus walks in or until they arrest me” [VIDEO] ...

The following article, BREAKING: Ex-Cop Father and Son Arrested and Charged With Murder of Black Man Jogging In Neighborhood…President Trump Responds [VIDEO], was first published on 100PercentFedUp.com.

The Georgia Bureau of Investigations has arrested a father and son duo, 64-year-old ex-cop, Gregory McMichael, and his son, 34-year-old Travis McMichael for the February murder of  24-year-old Ahmaud Arbery, a black man who was jogging through their neighborhood when they jumped in their truck and pursued him. Yashar Ali shared the news of the […]

Continue reading: BREAKING: Ex-Cop Father and Son Arrested and Charged With Murder of Black Man Jogging In Neighborhood…President Trump Responds [VIDEO] ...

pncRNA-D is an irradiation-induced 602-nt long noncoding RNA transcribed from the promoter region of the cyclin D1 (CCND1) gene. CCND1 expression is predicted to be inhibited through an interplay between pncRNA-D and RNA-binding protein TLS/FUS. Because the pncRNA-D–TLS interaction is essential for pncRNA-D–stimulated CCND1 inhibition, here we studied the possible role of RNA modification in this interaction in HeLa cells. We found that osmotic stress induces pncRNA-D by recruiting RNA polymerase II to its promoter. pncRNA-D was highly m6A-methylated in control cells, but osmotic stress reduced the methylation and also arginine methylation of TLS in the nucleus. Knockdown of the m6A modification enzyme methyltransferase-like 3 (METTL3) prolonged the half-life of pncRNA-D, and among the known m6A recognition proteins, YTH domain-containing 1 (YTHDC1) was responsible for binding m6A of pncRNA-D. Knockdown of METTL3 or YTHDC1 also enhanced the interaction of pncRNA-D with TLS, and results from RNA pulldown assays implicated YTHDC1 in the inhibitory effect on the TLS–pncRNA-D interaction. CRISPR/Cas9-mediated deletion of candidate m6A site decreased the m6A level in pncRNA-D and altered its interaction with the RNA-binding proteins. Of note, a reduction in the m6A modification arrested the cell cycle at the G0/G1 phase, and pncRNA-D knockdown partially reversed this arrest. Moreover, pncRNA-D induction in HeLa cells significantly suppressed cell growth. Collectively, these findings suggest that m6A modification of the long noncoding RNA pncRNA-D plays a role in the regulation of CCND1 gene expression and cell cycle progression.

The ribosome biogenesis factor Las1 is an essential endoribonuclease that is well-conserved across eukaryotes and a newly established member of the higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain-containing nuclease family. HEPN nucleases participate in diverse RNA cleavage pathways and share a short HEPN nuclease motif (RφXXXH) important for RNA cleavage. Most HEPN nucleases participate in stress-activated RNA cleavage pathways; Las1 plays a fundamental role in processing pre-rRNA. Underscoring the significance of Las1 function in the cell, mutations in the human LAS1L (LAS1-like) gene have been associated with neurological dysfunction. Two juxtaposed HEPN nuclease motifs create Las1's composite nuclease active site, but the roles of the individual HEPN motif residues are poorly defined. Here using a combination of in vivo experiments in Saccharomyces cerevisiae and in vitro assays, we show that both HEPN nuclease motifs are required for Las1 nuclease activity and fidelity. Through in-depth sequence analysis and systematic mutagenesis, we determined the consensus HEPN motif in the Las1 subfamily and uncovered its canonical and specialized elements. Using reconstituted Las1 HEPN-HEPN' chimeras, we defined the molecular requirements for RNA cleavage. Intriguingly, both copies of the Las1 HEPN motif were important for nuclease function, revealing that both HEPN motifs participate in coordinating the RNA within the Las1 active site. We also established that conformational flexibility of the two HEPN domains is important for proper nuclease function. The results of our work reveal critical information about how dual HEPN domains come together to drive Las1-mediated RNA cleavage.

20 April 2020

Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in the 21st century. Researchers at Chatham House have worked with eight experts to produce this collection of essays examining four contested themes in contemporary policymaking on deterrence.

7 May 2020 , Volume 96, Number 3

RK Tangirala
Nov 1, 1995; 36:2320-2328
Articles

7 May 2020 , Volume 96, Number 3