"This may become the new normal." The fitness and beauty industries may look much different after Indiana's coronavirus stay-at-home order is lifted.

An insurance payment due to Victor Oladipo's injury gives Pacers lowest payroll in NBA

Ireland captain Laura Delany says she gained valuable insights into the importance of mental preparation as Meg Lanning joins Isobel Joyce for a virtual batting session.

The transport secretary warns social distancing will mean severely-reduced passenger capacity.

Simon Bogg says it took him 10 days to make the sculpture in tribute to the "absolute legend".

A family of four was able to safely get out of their house after a fire caused $200,000 of damage.

F1 driver Lando Norris calls McLaren fan Captain Tom Moore after the 99-year-old raised more than £27m for the NHS by completing 100 laps of his garden.

Formula 1 bosses will meet this week to discuss a reduction of the budget cap figure to $145m (£117m) in 2021.

Europeans face a blizzard of restrictions on their freedoms as authorities try to stop the spread.

Scientists map ancient underwater landslides in the region chosen for Jakarta's replacement.

One of the hardest tasks in Earth observation is tracking tiny changes in the shape of the ground.

Certain habitats can help dampen the spread of ash dieback, which threatens ash trees.

A chronology of key events

Key facts, figures and dates

The scenes they draw include a senator seemingly falling asleep.

Pulitzer-winning cartoonist Mike Luckovich had a middle-of-the-night inspiration after Super Tuesday.

• As the coronavirus-led economic shutdown drags on, many investors have started counseling startups to have more than a years' worth of "runway" to avoid having to raise funding on poor terms.
• But VCs are split on how much startups should be socking away. Some have estimated 18 months oof reserves could suffice, while others say as much as 3 years' worth of runway is ideal.
• The different time frames depends on the age of the startup along with which industry they operate in. Younger startups typically have fewer overhead expenses, while older startups likely have more employees and pricey office leases.
• Also, those companies that may be able to resume work as essential services may need less cash if they are able to generate revenue.
• VCs are uniformly bracing for an economic slowdown, but the severity of downturn is still up for debate. 
• Click here for more BI Prime stories.

Startups are facing what could become the worst economic downturn in several decades, and VCs are begging them to take drastic measures to improve their chances of making it through. 

Most Americans who lived through the 2008 financial crisis will know that a savings stockpile or rainy day fund can mean the difference between surviving and thriving during tough times, but as recent studies have shown, many tech startups and VC firms don't have a similar first-hand experience; many have only known boom times and are now venturing into uncharted waters.

One thing VCs agree on is that startups need to quickly rein in growth plans — ideally as soon as yesterday — and start scrutinizing expenses. Anything nonessential should be cut or suspended indefinitely, headcount should be reduced, and pricey office leases eliminated if possible, all with the goal of extending a startup's "runway."

In Silicon Valley, runway refers to how much cash a startup has on hand to put against its operating expenses. If, for example, a startup has roughly $100,000 in monthly operating expenses and has $1 million in the bank, they are looking at a 10-month runway, assuming revenue stays roughly flat.

In the days before the coronavirus pandemic, a startup's runway dictated when it had to start looking for additional funding. Instead of cutting expenses, the popular solution was to simply put more VC money in the bank. This helped high flying startups like Uber and Airbnb expand at a breakneck pace — VC dollars kept pouring in and the companies remained unprofitable as they chased growth at all costs.

But now, VCs are saying that's no longer an option. Founders Fund general partner Keith Rabois said on a podcast recently that profitability is now being rewarded much more than high-growth. 

For startups that aren't profitable, that means hunkering down and ensuring there are enough reserves to last through the crisis.

So how long does the runway need to be? 

Many VCs that Business Insider has spoken to are advising their startups to have at least 18 months of runway. But some VCs say startups should have upwards of 3 years' of expenses saved up. 

The length of time can vary depending on the startup, one investor told Business Insider, pointing to the startup's age and industry as important factors. An early-stage company with a handful of employees and low-overhead costs might easily stretch a $500,000 seed check, whereas a growth-stage biotech startup with hundreds of employees, expensive hardware, and pricey office space might struggle to make tens of millions of dollars in funding make it through 12 months. Those that can't cut costs will be forced to fundraise with poor terms and risk the dreaded downround. 

"You can always easily dial back up the aggressiveness and risk profile if we get more optimistic visibility, but if you don't take action right away — to preserve capital, cut your burn rate, have fundamentally attractive unit economics, edit the product to make more sense in the new world order — if you don't do those right away, the opportunity to do those things and survive is probably lost forever," Rabois said in the April Talkshow broadcast.

Rabois is in the camp of pessimists, generally speaking, who think the economic downturn will not only drag on through 2020, but could eventually turn into an economic depression the likes of which could rival the Great Depression of the 1930s. He said that his VC peers are starting to rein in the freewheeling deal-making that has defined the last two decades of the Silicon Valley startup ecosystem, and are now treading cautiously. It's time that startups do the same, he said.

SEE ALSO: Lower valuations and a long wait for funding: Two top early-stage VCs dish on how they are counseling startups to withstand long-term economic uncertainty

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Laine Hardy and Maelyn Jarmon may have won different shows, but their experiences are very similar.

Tim Alberta's new book chronicles a decade of GOP recklessness, cowardice and excuses

If you don’t know what capital gains indexing to inflation means, you probably wouldn’t benefit from it.

It wasn’t one of my proudest moments when, a week before Christmas last year, I was hunched over my smartphone towards the back of the famous Hamley’s Toy Store on London’s Regent Street, composure tethered to an elusive bar of …

As the Western Cape ramps up its screenings and testing for Covid-19 as confirmed cases rise, the ANC in the province is calling for the return to Level 5 lockdown to be considered.

Seventeen more Covid-19-related deaths have been recorded in the country, bringing the number to 178, while the biggest one-day spike in new cases hit 663.

An investigation over several months has revealed how Coca-Cola ignored the water-saving regulations and how the City of Cape Town failed to take any action.

This episode of Tali's Wedding Diary is proudly shared with you by Channel24 and Showmax.

Stay up to date with the latest news, views and analysis as the number of coronavirus cases in SA increases.

Cosatu in the Western Cape says that it is deeply concerned over the "alarming rate on increase" in Covid-19 infections in the province.

The Economic Injury Disaster Loan program is now limiting both the amount and recipients it will consider for the emergency loans.

Cape Town, South Africa

Amateur Traveler talks to Matt Kepkes of NomadicMatt.com about his trip to the ancient capitals of Thailand: Ayutthaya, Lopburi and Sukhothai. Before the capital moved to Bangkok it was in each of these three cities as invaders came in from what is now Cambodia and Burma and then were subsequently repelled. Instead of taking the night train to Chang Mai as many tourists do, Matt and his traveling companions explored these cities on the way. In their travels they found ancient temples (some in ruins and some well preserved), wonderful night markets, troops of monkeys, friendly people and a slice of rural Thailand.

Hear about cruising from Buenos Aires, Argentina to Valparaiso, Chile around Cape Horn in South America as the Amateur Traveler relates stories of a recent Holland America cruise on the Zaandam. 

Hear about travel to Cape Town, South Africa as the Amateur Traveler talks to Annika Ziehen from Midnight Blue Elephant about her former hometown

In 1971, a man named Gregory Harris was murdered. Richard Phillips, an autoworker, was convicted of the crime and spent the next 45 years in prison. The problem? Phillips was innocent. Instead, it was the star witness during the trial who framed Phillips, and it took his alleged partner-in-crime, Richard Polombo, decades to admit that…

The post He Spent 45 Years in Prison for Crime He Didn’t Commit, Turned to Art as His Escape appeared first on The Western Journal.

It’s not good for people to be alone. Quarantining has been difficult for many people who have gotten used to socializing daily, and because of that, some have found ways to follow the rules but feel a little less isolated. Some neighborhoods have decided to be social while maintaining the suggested distance apart, whether that’s…

The post ‘The Voice’ Contestant Alexa Cappelli Treats Neighbors to Weekly Performance in Her Cul-de-Sac appeared first on The Western Journal.

Zoom has become a way of life for some people as of late (despite, uh, some safety concerns), especially when it comes to work meetings. Whether it's a company-wide all hands or a team check-in, it's likely that if you're working from home due to the coronavirus pandemic, you've had to see your coworkers' shining faces in a video call. 

Actor, writer, and Groundlings comedian Caitlin Reilly perfectly encapsulated that one co-worker you just can't stand during these video meetings:

It's so relevant it hurts. Who hasn't heard the phrase "to piggyback off of" during one of these calls?

The inspiration behind the 'tok was experiences Reilly had sitting in Zoom meetings on behalf of her boss. "I had actually never been in a zoom meeting before, so it was funny for me to see all the different 'personality' types in a situation like that," Reilly told Mashable. "And so it popped in my head one day and I just made the video." Read more...

Former Proteas head coach Ray Jennings is adamant Aiden Markram should be chosen as Faf du Plessis' replacement as captain of the Test team.

Before I start recapping the month, let me begin with a greeting: “Hey, Kate from the future! Hey, people who were curious! I knew you’d look up this post! How are you doing? By the way, just how long is this going to last?!” Because this is the recap for March 2020 — a month …

AK Monthly Recap: March 2020 Read More »

The post AK Monthly Recap: March 2020 appeared first on Adventurous Kate.

Is it just me, or did this month majorly speed up? March 2020, the month that coronavirus ramped up enormously, was the longest month of my life. I know it was for many of you, too. By comparison, April seemed to go by in 10 days. This month the hardest decision of my life — …

AK Monthly Recap: April 2020 Read More »

The post AK Monthly Recap: April 2020 appeared first on Adventurous Kate.

Labour laws haven’t changed in our province, but legal experts are already urging B.C. employers to be flexible and reasonable — while warning employees they may not be legally protected if they refuse work during the pandemic.

Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505–527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515–519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function.

Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505–527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515–519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function.

Invitation Only Research Event

Event participants

Megan Greene, Managing Director and Chief Economist, Manulife Asset Management 

Corporate Members Event Webinar

Event participants

Neil Walsh, Chief, Cybercrime and Anti-Money Laundering Department, UN Office of Drugs and Crime

Lisa Quest, Head, Public Sector, UK & Ireland, Oliver Wyman

Chair: Joyce Hakmeh, Senior Research Fellow, International Security Programme; Co-Editor, Journal of Cyber Policy, Chatham House

Further speakers to be announced.

Actinobacillus pleuropneumoniae (App) is the etiological agent of acute porcine pneumonia and responsible for severe economic losses worldwide. The capsule polymer of App serotype 1 (App1) consists of [4)-GlcNAc-β(1,6)-Gal-α-1-(PO4-] repeating units that are O-acetylated at O-6 of the GlcNAc. It is a major virulence factor and was used in previous studies in the successful generation of an experimental glycoconjugate vaccine. However, the application of glycoconjugate vaccines in the animal health sector is limited, presumably because of the high costs associated with harvesting the polymer from pathogen culture. Consequently, here we exploited the capsule polymerase Cps1B of App1 as an in vitro synthesis tool and an alternative for capsule polymer provision. Cps1B consists of two catalytic domains, as well as a domain rich in tetratricopeptide repeats (TPRs). We compared the elongation mechanism of Cps1B with that of a ΔTPR truncation (Cps1B-ΔTPR). Interestingly, the product profiles displayed by Cps1B suggested processive elongation of the nascent polymer, whereas Cps1B-ΔTPR appeared to work in a more distributive manner. The dispersity of the synthesized products could be reduced by generating single-action transferases and immobilizing them on individual columns, separating the two catalytic activities. Furthermore, we identified the O-acetyltransferase Cps1D of App1 and used it to modify the polymers produced by Cps1B. Two-dimensional NMR analyses of the products revealed O-acetylation levels identical to those of polymer harvested from App1 culture supernatants. In conclusion, we have established a protocol for the pathogen-free in vitro synthesis of tailored, nature-identical App1 capsule polymers.

3-Mercaptopyruvate sulfur transferase (MPST) catalyzes the desulfuration of 3-mercaptopyruvate (3-MP) and transfers sulfane sulfur from an enzyme-bound persulfide intermediate to thiophilic acceptors such as thioredoxin and cysteine. Hydrogen sulfide (H2S), a signaling molecule implicated in many physiological processes, can be released from the persulfide product of the MPST reaction. Two splice variants of MPST, differing by 20 amino acids at the N terminus, give rise to the cytosolic MPST1 and mitochondrial MPST2 isoforms. Here, we characterized the poorly-studied MPST1 variant and demonstrated that substitutions in its Ser–His–Asp triad, proposed to serve a general acid–base role, minimally affect catalytic activity. We estimated the 3-MP concentration in murine liver, kidney, and brain tissues, finding that it ranges from 0.4 μmol·kg−1 in brain to 1.4 μmol·kg−1 in kidney. We also show that N-acetylcysteine, a widely-used antioxidant, is a poor substrate for MPST and is unlikely to function as a thiophilic acceptor. Thioredoxin exhibits substrate inhibition, increasing the KM for 3-MP ∼15-fold compared with other sulfur acceptors. Kinetic simulations at physiologically-relevant substrate concentrations predicted that the proportion of sulfur transfer to thioredoxin increases ∼3.5-fold as its concentration decreases from 10 to 1 μm, whereas the total MPST reaction rate increases ∼7-fold. The simulations also predicted that cysteine is a quantitatively-significant sulfane sulfur acceptor, revealing MPST's potential to generate low-molecular-weight persulfides. We conclude that the MPST1 and MPST2 isoforms are kinetically indistinguishable and that thioredoxin modulates the MPST-catalyzed reaction in a physiologically-relevant concentration range.