Until we have a vaccine, the road to opening is through a health care system which can handle the infection, a letter to the editor says.

The al-Hota gorge became "a place of horror" under the jihadist group, Human Rights Watch says.

The three affected newspapers deplored what they said was an unprecedented attack on press freedom.

Boris Johnson's chief scientific adviser says the UK is four weeks behind Italy, What does that mean?

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5. Anushka Sharma, Virat Kohli kiss and cuddle in throwback pic from a snowy vacation  Hindustan Times
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4. Buoyed by Ramayans record-breaking run, Kapil Sharmas episode with stars to air again - Republic World  Republic World
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As COVID-19 continues to shut down sporting events across the globe, a former Roughriders’ CEO says it could be the greatest threat the CFL has ever faced.

Eisner-winning cartoonist Brian Fies faces down another fire two years after losing his Northern California home. "I'm mostly numb," he says.

Pulitzer-winning editorial artists aim to find deadline satire in the televised inquiry.

And, of course, an opportunity.

"Onward" and "Soul" deal with the eternal and the ethereal.

Three years ago it was barely walking. Now, Atlas, the humanoid robot from Boston Dynamics is performing gymnastic routines that mimic professional athletes.

But they should make the playoffs!

The key could be Dedric Lawson, a 6-foot-9 forward who sat out last season after transferring from Memphis and is the best transfer Coach Bill Self has landed in his time in Lawrence.

Lamar Jackson, the 2016 Heisman Trophy winner and first round pick in the 2018 NFL draft, produced 117 rushing yards against the Bengals. Fantasy owners should take notice.

Almost everyone who played for the Thunder in 2017-18 and is also getting major minutes this season has improved their individual defensive rating.

• The storied investment bank is seeing leadership shakeups under CEO David Solomon and a slew of partner departures. 
• Goldman has been moving away from high-risk businesses like trading and is making pushes into more stable areas like consumer lending, wealth management, and transaction banking. 
• There have been big cultural changes, too. Solomon is looking to create a more transparent workplace, while new tech execs are taking cues from Silicon Valley heavy-hitters. 
• At Business Insider, we are closely tracking the latest developments at Goldman. You can read all of our Goldman coverage on BI Prime.

Storied Wall Street bank Goldman Sachs is going through some massive changes under CEO David Solomon.

It's taken big steps involving transparency and inclusion to change up its culture. It has seen a slew of partner departures — many in the securities division. And it's making big pushes into businesses like wealth management and transaction banking.  

The latest people moves

• Goldman Sachs just hired Kurt Hoffman, an expert in distressed situations and bankruptcy, to join a trading unit known for some of the bank's most lucrative deals
• Goldman Sachs' top tech exec explains how a fresh slew of senior hires are transforming the bank's approach to building products
• Read the full memo Goldman Sachs just sent naming 4 execs to lead its private-equity investments across the merchant-banking division

Culture and talent

• Read the full memo Goldman Sachs just sent to staff announcing its new head of regulatory affairs. The former White House counsel will be tasked with helping clean up the bank's 1MDB drama.
• Goldman Sachs just hired 2 senior recruiting execs focused on luring top talent from other firms —and it's a huge departure from the firm's traditional promote-from-within mentality
• Read the full memo David Solomon just sent to 38,000 Goldman Sachs employees explaining why he's moving his management team out of stuffy offices and into open seating
• Goldman Sachs CEO David Solomon and his management team are ditching their stuffy offices and moving to an open floor plan closer to the people so they can feel the buzz of New York headquarters
• Goldman Sachs just unveiled a new gender pronouns initiative as part of a broader inclusion push at the Wall Street firm
• Read the memo Goldman Sachs just sent to its employees unveiling a new pronouns initiative

Coronavirus response

• Inside a 38,000-person remote work rollout at Goldman Sachs: sleepless nights, assembly lines, and an Amazon-like hub on a Manhattan trading floor
• How a massive New York hospital secured 130,000 N95 masks from China with help from a senior partner at Goldman Sachs, private jets, and a call to Warren Buffett
• Goldman Sachs CEO David Solomon just sent a firm-wide voicemail about the coronavirus crisis. Here's what he told employees.
• Goldman Sachs and Bank of America just updated their WFH policies — again. Here's what they're telling employees about the latest steps aimed at combating the spread of coronavirus.
• Read the full memo Goldman Sachs top brass just sent detailing the firm's coronavirus contingency plans, including separating employees into 'blue' and 'white' teams to alternate working from the office and home

Consumer push, transaction banking, wealth management

• Goldman Sachs just announced its first partnership for transaction banking as it looks to build a new $1 billion business moving money around the world
• Goldman Sachs is sending much less mail to potential Marcus customers. A senior exec lays out the reason why.
• A Goldman Sachs exec explains why the bank isn't sweating concerns over the Apple Card's profitability
• A Wall Street firm crunched the numbers around how much Apple will make from its new credit card with Goldman Sachs
• Here's why Goldman Sachs just did its biggest deal in nearly 20 years as part of a pivot to less wealthy clients
• Goldman Sachs execs are opening up about their plans for Marcus, and they think it can do to banking what iTunes did to the music industry
• Goldman Sachs' partnership with Apple could move it a step closer to being 'a bank branch in your pocket'
• Human resources is the next battleground for Wall Street wealth advisers as Morgan Stanley and Goldman Sachs jockey over new turf
• Goldman Sachs has a novel method for predicting the next economic slump, and it's at the heart of its hot new business

Technology

• JPMorgan and Goldman Sachs are finally beginning to embrace fintech startups. Here's how they test the waters before committing to working with them.
• We talked to the execs behind Bloomberg's new data partnership with Goldman Sachs. Here's why they think it's a sign of Wall Street's future.
• Goldman Sachs is putting its own Marquee app on Amazon's cloud in a pitch to lure more fintech developers
• Goldman Sachs is embracing open-source code and its chief data officer says it's part of a "new world" of software
• Read the memo the new Goldman tech chief sent to the firm's 9,000-plus engineers where he urges them to ditch presentations in favor of Amazon's famous narratives
• A new Goldman Sachs tech exec hired from Amazon is taking a page from the Jeff Bezos playbook by urging engineers to ditch PowerPoint and write memos
• Goldman Sachs' new CTO shares his strategy for attracting outside developers to work more closely with the bank, giving a glimpse into the future of how Wall Street will work
• A Verizon executive is joining Goldman Sachs as chief technology officer as the Wall Street bank reshuffles its ranks
• Marty Chavez is retiring from Goldman Sachs. We chatted with him about the bank's tech transformation, why now is the right time for him to step down, and what he's planning next.
• Goldman Sachs tech guru Marty Chavez is retiring from the bank
• Goldman Sachs' CEO just warned that the bank's big tech bets might not pay off as quickly as people hope
• Goldman Sachs is scrapping a homegrown email app it once touted — and it's a sign the bank is moving away from building tech in house
• Goldman Sachs is exploring plans to create a Netflix for data, and it marks a new frontier for Wall Street
• Goldman Sachs' internal idea factory hatched a plan for the Google of Wall Street, and it's now looking for the next big thing to disrupt the bank
• Goldman Sachs' big bet on the future of Wall Street had a rocky start. Here's the inside story of the bank's struggle to grow its next business and an exclusive look at its plans

Trading

• Bank of America is shaking up its global markets division and poached a Goldman Sachs exec to fill a key new role
• Goldman Sachs' massive quant business now rivals AQR and Two Sigma. We talked to the bank's top quant about asset growth, finding data sources, and why critics of computerized trading are wrong.
• Goldman Sachs' CEO tells us the bank is winning over quant clients. That helped it outpace rivals like JPMorgan last quarter.
• Goldman Sachs is cutting about 5% of sales and trading staff after senior equities leaders delivered a tough town-hall talk
• Goldman Sachs is moving away from a tool championed by its former CFO as it pushes its traders to see clients where they once saw quick wins
• Goldman Sachs is shuffling its top stock trading executives as the business tries to claw back market share from Morgan Stanley and JPMorgan
• Goldman Sachs's bond trading unit is still trying to find its way — and it represents a key challenge for new CEO David Solomon

Alternatives

• Read the full memo Goldman Sachs just sent naming 4 execs to lead its private-equity investments across the merchant-banking division
• Goldman Sachs is making targeted hires for a 'storefront' for alternative investments that's modeled after firms like KKR and Blackstone
• Goldman Sachs' push into private equity is ruffling feathers at Blackstone — and it might be a sign of big client skirmishes to come
• Goldman Sachs execs are jockeying for control of the firm's lucrative private investing units after a plan to merge it — and the stakes couldn't be higher
• Meet the Goldman Sachs execs tasked with building the firms' new Blackstone-esque private-investing unit — and pumping up the bank's flagging stock price
• 'It's good to be Rich': Meet the Goldman Sachs banker who has built a private investing empire that goes head-to-head with Blackstone — and you've probably never heard of him
• Goldman Sachs is considering a shakeup of its alternative investing units as part of a plan to simplify the bank's strategy

Deals

• Goldman Sachs is assembling a team of senior bankers focused on middle-market private equity. Here are the key hires and the playbook they'll use to land new clients.
• Goldman Sachs unloaded some of its WeWork shares before its investment bankers pitched investors on what it once considered a $60 billion-plus IPO
• Goldman Sachs just revealed it sold part of its Uber stake to SoftBank and it helped boost a $4.5 billion business
• A senior Goldman Sachs fintech banker was about to join JPMorgan — but then got lured back —and it's another sign of the fierce battle for M&A talent
• Goldman just promoted a star tech banker close to Tesla and Microsoft to co-head one of its most profitable businesses, as incoming CEO Solomon makes his mark
• Goldman Sachs just announced a shakeup of its leadership — and it signals the rise of bankers over traders
• A tug-of-war between Goldman Sachs and JPMorgan over a top banker highlights Wall Street's $1 trillion battleground

Investor day 2020

• Inside Goldman Sachs' first investor day, where avocado toast and crab apples were served with tech talk, 3-year plans, and a surprising trading mea culpa
• Goldman Sachs just revealed a new wealth brand at its first-ever investor day. It shows how the bank is trying to reshape its strategy — and image.
• Goldman Sachs just unveiled hundreds of slides laying out the future of the company. Here are the 10 crucial slides that show how it plans to transform into a bank for everyone.
• Goldman Sachs is rethinking how it makes private-equity bets with its own money – and one analyst thinks that shift will be a big driver of its stock price

Careers 

• Goldman Sachs is now hiring high-school graduates for roles in Salt Lake City, one of the company's 'high value' locations
• Goldman Sachs has lost at least 54 partners since David Solomon became CEO. We're keeping a running list — and compiling details from insiders about how the exits are being celebrated.
• Read the full memo Goldman Sachs' top brass just sent to staff announcing 2 heads of the bank's private-investing arm are out as it's gearing up to raise billions
• 2 coheads of Goldman Sachs' private-investing business are retiring, in a blow to David Solomon's fundraising plans
• A Goldman Sachs partner who just resigned is leaving behind a job overseeing $2 billion for a London VC with a leading stake in neobank Revolut
• Read the memo announcing the departure of Adam Korn, the Goldman Sachs exec who was 'instrumental in building and championing' innovations like the bank's Marquee platform
• Another Goldman Sachs partner is out. HR chief Dane Holmes is the latest key player to leave the Wall Street bank in a matter of days.
• Goldman Sachs is offering buyouts to encourage partners to leave as CEO David Solomon works to shrink one of the most elite clubs on Wall Street
• Goldman Sachs is making renewable energy a big priority based on its hiring strategy. It's a sign that its ideas incubator is working.
• The David Solomon era at Goldman Sachs kicked off with 43 words Lloyd Blankfein would never say
• Goldman Sachs CEO David Solomon shares his best leadership advice
• Goldman Sachs is shaking up the way it stocks one of the most elite clubs on Wall Street — and it shows how banks are back to making money again
• Goldman Sachs' 1MDB problems are eating into employee morale, and insiders worry the firm will use its legal woes as an excuse to scrimp on bonuses
• Goldman Sachs is about to move dozens of jobs out of pricey New York to Utah as Wall Street turns to cheaper cities

Join the conversation about this story »

NOW WATCH: A cleaning expert reveals her 3-step method for cleaning your entire home quickly

The Fox Nation host got plenty of criticism for her tweet about the Democratic presidential candidate — including from fellow Fox-ers.

Sen. Elizabeth Warren embraced her latest celebrity endorsements. "Looking forward to the day @chrissyteigen doesn't have to fight with the president of the United States on Twitter," she said.

When it comes to getting schooled on plastic water bottles, look no further than Aquaman.

You may be aware that cyber attacks will try to trick you over the phone or through email using phishing attacks, but do you realize they may try to attack you also over Social Media, such as through Snapchat, Twitter, Facebook or LinkedIn? Just like in email, if you get any Social Media messages that are highly urgent or too good to be true, it may be an attack.

As demand at food banks has surged, donations from local grocers and supermarkets have plummeted.

strataconf: A roundup of healthcare tools used in the field from #hdpalooza http://t.co/0d2x3OlaeC including @MedCPU @SVBiosystems @CHRankings & more

The equipment donated includes 20 000 laboratory diagnostic test kits, 100 000 medical masks, and 1 000 protective suits and face shields.

Tesla CEO Elon Musk said Saturday the company will file a lawsuit against Alameda County and threatened to move its headquarters and future programs to Texas or Nevada immediately, escalating a fight between the company and health officials over whether its factory in Fremont can reopen. Tesla had planned to bring back about 30% of […]

Yesterday was a really fun day spent at Nokia World, the Finnish handset maker’s annual shindig. Conveniently, this year it was held in my home city of London and I got to cover the event for TechCrunch Europe. On day one, Nokia unveiled three new smartphones running Symbian^3, the C6, C7 and E7, which I [...]

velocityconf: @tsantero @garethr No, there's just a lot that goes into producing #velocityconf. Plus the chairs are getting ready for Santa Clara + NY! :)

Are you dreaming of being your own boss someday, or would you like to bring in extra income? Starting an online business is one of the easiest ways to accomplish this. The biggest challenge of starting an online business can be developing your business plan. If you are struggling to come up with that brilliant […]

Travel Photography (interview with Chris Marquardt)

Biking Through Honduras, Guatemala and Belize

Through Hiking the Pacific Crest Trail at 10

The Amateur Traveler talks to Ira Bernstein about two lesser visited cities in Italy - Turin and Bologna. Turin has the reputation as the Detroit of Italy because of its long association with Fiat but that nickname does not express the beauty of the city, the warmth of its people nor the quality of its wine. Bologna has a reputation for good food in a country known for its good food which may be one of the reasons that Bologna is known as "the fat". The city is the home of bolognese sauce and lasagna. It also lays claim to one of the oldest if not the oldest university in Europe. Ira takes us on a tour of surprising museums (like the largest Egyptian museum outside Cairo), pivotal history and of course wonderful food. 

The Amateur Traveler talks to Lee from Atlanta about side trips that you can take when you travel to Shanghai this year for Expo 2010. Lee is currently living in China and talks about 3 different weekend trips to destinations that are located near Shanghai. Lee starts us the in history-rich city of Nanjing the site of “China’s Holocaust” in WW 2. Nanjing has been the capital for 6 different Chinese governments and still retains its ancient walls in addition to modern shopping and the tomb of Sun Yat-sen. It was also the location of the world’s worst civil war, the Taiping Rebellion. After Nanjing we explore the many gardens and the canals of Suzhou. Finally Lee takes us to Hangzhou with its beautiful West Lake which the Chinese compare to heaven.

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Show Notes

Expo 2010 Shanghai China
Travel to Shanghai, China – Episode 26

Nanjing
Nanjing, China
Nanking Massacre
John Rabe – a German businessman and Nazi party member who is best known for his efforts to stop the atrocities of the Japanese army during the Nanking Occupation
Sun Yat-sen – “Father of the Chinese Nation”
Ming Dynasty
Cheongsam or Qipao – traditional Chinese dress
Taiping Rebellion – largest civil war in history started by Hong Xiuquan who declared himself the brother of Jesus.

Restaurants
Skyway Bakery and Deli
Les 5 Sens
Tairyo Teppanyaki

Suzhou
Gardens – Master of the Nets, Lion’s Forest, Humble Administrator
Mingtown Suzhou International Youth Hostel

Hangzhou
Tea Museum
A History of Chinese in California
Braised Pork Belly – Hangzhou Dongpo Pork
Sweet and Sour Pork Recipe
Wushanyi International Youth Hostel

Shanghai
Captain Youth Hostel

elong.com, ctrip.com – for accompodations

Community

Egypt Photo Tour
Amateur Traveler Newsletter
Does Amateur Traveler work for you at work?

The Amateur Traveler talks to Lee Abbamonte, the youngest American ever to travel to every country in the world, about 3 islands off the coast of Australia: Lord Howe Island, Norfolk Island, Christmas Island.

In preparation for the 2017 500th anniversary of the Reformation, Chris (the Amateur Traveler) took a road trip through "Luther Land" and the heart of Germany.

A transit centre in north Edmonton was evacuated for about two hours Saturday morning due to a suspicious package.

Christmas is not an official holiday in Japan, nor a widely observed religious holiday, but it is celebrated nonetheless in its own unique way. Here's some data that highlights Christmas in Japan.

An "appalling prank" in Innisfil sent South Simcoe Police officers on a mission to identify the culprits involved.

The following article, Univ of Pittsburg Researcher, China Native, Dr. Bing Liu, “On the verge” of COVID19 Breakthrough Is Murdered…Alleged Gunman, Hao Gu, Kills Himself, was first published on 100PercentFedUp.com.

A 37-year-old China native and "outstanding researcher" at the University of Pittsburgh...

Continue reading: Univ of Pittsburg Researcher, China Native, Dr. Bing Liu, “On the verge” of COVID19 Breakthrough Is Murdered…Alleged Gunman, Hao Gu, Kills Himself ...

The following article, Woman Shoots Three Teenage McDonald’s Workers For Telling Her She Couldn’t Eat In Dining Room Over COVID19 Restrictions, was first published on 100PercentFedUp.com.

An angry Oklahoma woman shot at a group of teenagers working at a local McDonald’s after they explained to her that the dining room was closed due to coronavirus restrictions. 32-year-old Gloricia Woody was arrested by the Oklahoma City Police and charged with the shooting. From the Oklahoma City Police -Last night, officers were called […]

Continue reading: Woman Shoots Three Teenage McDonald’s Workers For Telling Her She Couldn’t Eat In Dining Room Over COVID19 Restrictions ...

The atypical trichromatic cyanobacterial phytochrome NpTP1 from Nostoc punctiforme ATCC 29133 is a linear tetrapyrrole (bilin)-binding photoreceptor protein that possesses tandem-cysteine residues responsible for shifting its light-sensing maximum to the violet spectral region. Using bioinformatics and phylogenetic analyses, here we established that tandem-cysteine cyanobacterial phytochromes (TCCPs) compose a well-supported monophyletic phytochrome lineage distinct from prototypical red/far-red cyanobacterial phytochromes. To investigate the light-sensing diversity of this family, we compared the spectroscopic properties of NpTP1 (here renamed NpTCCP) with those of three phylogenetically diverged TCCPs identified in the draft genomes of Tolypothrix sp. PCC7910, Scytonema sp. PCC10023, and Gloeocapsa sp. PCC7513. Recombinant photosensory core modules of ToTCCP, ScTCCP, and GlTCCP exhibited violet-blue–absorbing dark-states consistent with dual thioether-linked phycocyanobilin (PCB) chromophores. Photoexcitation generated singly-linked photoproduct mixtures with variable ratios of yellow-orange and red-absorbing species. The photoproduct ratio was strongly influenced by pH and by mutagenesis of TCCP- and phytochrome-specific signature residues. Our experiments support the conclusion that both photoproduct species possess protonated 15E bilin chromophores, but differ in the ionization state of the noncanonical “second” cysteine sulfhydryl group. We found that the ionization state of this and other residues influences subsequent conformational change and downstream signal transmission. We also show that tandem-cysteine phytochromes present in eukaryotes possess similar amino acid substitutions within their chromophore-binding pocket, which tune their spectral properties in an analogous fashion. Taken together, our findings provide a roadmap for tailoring the wavelength specificity of plant phytochromes to optimize plant performance in diverse natural and artificial light environments.

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.

Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin–Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of WT PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor–like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights into ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies.

6 January 2020

26 February 2020

Over the past two decades, China has increased its presence in North Africa in terms of trade and investment. This paper looks at China’s policy within the context of its Africa and Middle East policies to better understand its approach to Morocco and Tunisia.

Extracytoplasmic sugar decoration of glycopolymer components of the bacterial cell wall contributes to their structural diversity. Typically, the molecular mechanism that underpins such a decoration process involves a three-component glycosylation system (TGS) represented by an undecaprenyl-phosphate (Und-P) sugar-activating glycosyltransferase (Und-P GT), a flippase, and a polytopic glycosyltransferase (PolM GT) dedicated to attaching sugar residues to a specific glycopolymer. Here, using bioinformatic analyses, CRISPR-assisted recombineering, structural analysis of cell wall–associated polysaccharides (CWPS) through MALDI-TOF MS and methylation analysis, we report on three such systems in the bacterium Lactococcus lactis. On the basis of sequence similarities, we first identified three gene pairs, csdAB, csdCD, and csdEF, each encoding an Und-P GT and a PolM GT, as potential TGS component candidates. Our experimental results show that csdAB and csdCD are involved in Glc side-chain addition on the CWPS components rhamnan and polysaccharide pellicle (PSP), respectively, whereas csdEF plays a role in galactosylation of lipoteichoic acid (LTA). We also identified a potential flippase encoded in the L. lactis genome (llnz_02975, cflA) and confirmed that it participates in the glycosylation of the three cell wall glycopolymers rhamnan, PSP, and LTA, thus indicating that its function is shared by the three TGSs. Finally, we observed that glucosylation of both rhamnan and PSP can increase resistance to bacteriophage predation and that LTA galactosylation alters L. lactis resistance to bacteriocin.

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.

Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications.

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.