A WEEK into Winston Churchill's prime ministership in May 1940, the war was going disastrously. As Western Europe buckled in the face of the German onslaught, the Nazi regime looked invincible. Yet even in this dark hour, Churchill bristled with defiance. "I think I see my way through," he told his son Randolph.

HOW did you muddle through the longest weekend in world history? Here's how my other half and I botched the whole flipping thing up over at Feltz Towers. Following excellent advice, we were determined to have a structure, a schedule and stick to it.

A GoFundMe page aims to match the nearly $600,000 that Tia Stokes' non-profit dance group Kalamity has raised for people facing real-life calamities.

An Indianapolis photographer met a New Jersey painter on Instagram because they liked each other's work. Now they're married and run an art business.

Take this virus seriously and do your part to protect everyone in the community, a letter to the editors says.

Arlington High School alum Vivica A. Fox will speak at 7:15 p.m. Saturday, Feb. 10, as part of the Meet the Artists opening reception at Indianapolis Central Library. Her book, "Every Day I'm Hustling" will arrive in stores April 3.

Restaurant owner Roxy Taschuk wasn’t optimistic about the state of her industry when the COVID-19 pandemic hit.

Through his personal streaming platform, IndyCar veteran Conor Daly's Twitch offers fans a front-row seat to a driver's race-day mind.

I wondered about what the next generation of journalists thought about the movie's message, and about the tensions between the press and government.

Plainfield's volleyball team won nine matches in 2015. This year, they've won 11 matches already. Here's what changed.

All Avon schools will close through March 20 as one student has tested positive and a second student is showing symptoms of the novel coronavirus.

Teachers from North Elementary School in Noblesville decorated their cars and paraded through neighborhoods, waving and honking at students from afar during the closure of schools because of the coronavirus outbreak.

Indiana's K-12 schools will stayed closed through the end of the academic year as the state continues to fight the spread of the coronavirus.

There are 124 teams signed up for the Charlie Hughes Shootout, but the June 30 mandate of schools being closed throws the event in doubt.

Legislation that Indiana lawmakers tacked onto other bills received only the most perfunctory, if any, public vetting in the General Assembly.

Todd Yeagley is confident his players will carry out workouts and improve despite not being able to practice together.

Myles Turner of the Indiana Pacers discusses coronavirus and how his performance changed after the All-Star break

• 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

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.

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

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. 

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.

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 ...

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

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.

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.

Vitali Matyash
May 1, 2008; 49:1137-1146
Methods

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.

6 November 2019 , Volume 95, Number 6

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.

We asked Guardian readers living in cities and towns across the world to share their images of the wildlife they can see from their homes. You answered in your droves, from Canada to Cardiff, and here are some of the best.