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oscon: There's still time left to apply for #OSCON scholarships from @github + @newrelic. Deadline is 6/15 http://t.co/xQwx30jnaN

oscon: There's still time left to apply for #OSCON scholarships from @github + @newrelic. Deadline is 6/15 http://t.co/xQwx30jnaN




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strataconf: A roundup from the data journalism beat http://t.co/y8RVUwHO4G Global open data, scholarships, mapping a civil war & more #strataconf

strataconf: A roundup from the data journalism beat http://t.co/y8RVUwHO4G Global open data, scholarships, mapping a civil war & more #strataconf




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

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




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strataconf: TUE June 11 Best of Strata Webcast: Practical Strategies & Tactics for Moving to Big Data http://t.co/qn4gKSyBvw from #Strataconf + HW2012

strataconf: TUE June 11 Best of Strata Webcast: Practical Strategies & Tactics for Moving to Big Data http://t.co/qn4gKSyBvw from #Strataconf + HW2012




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News24.com | International Covid-19 wrap: Pakistan expats test positive, boy, 5, dies from 'disease caused by Covid-19'

Here is the latest news from around the world.




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velocityconf: Free webcast from our friends at @citrix 5/29 http://t.co/IOeY4U0wUP Learn to consolidate 40 load balancers and ADCs into single platform

velocityconf: Free webcast from our friends at @citrix 5/29 http://t.co/IOeY4U0wUP Learn to consolidate 40 load balancers and ADCs into single platform




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velocityconf: What Is the Risk That Amazon Will Go Down (Again)? http://t.co/DgnfQynjcM Thank you @bergstrom_johan for the awesome #velocityconf post.

velocityconf: What Is the Risk That Amazon Will Go Down (Again)? http://t.co/DgnfQynjcM Thank you @bergstrom_johan for the awesome #velocityconf post.




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News24.com | Don't let Malema divert attention from where it's needed most




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News24.com | Bleak future for young people if Ramaphosa can't deliver on his promises

With the working class resorting to online vouchers for groceries and the poor eating less bread than before, is it not impractical for the president to expect ordinary citizens to tighten their belts when MPs, Ministers and government officials' well-fed bellies belie the trouble the economy is in?




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News24.com | What can South Africa learn from the coronavirus?

What is needed is political will and proper governance in implementing these temporary measures and further planning in the event that the pandemic is prolonged or the possible eventuality of political risk in the near future.




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News24.com | Coronavirus: An open letter from Milan

Life as we knew it will definitely change after this, as firms realise that people can work from home, saving them money, the air is better without traffic and pollution and more and more courses and meetings take place online.




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Three Benefits of Promoting Digital Goods and Software Products

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 […]




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AT#73 - Bike tour from Vancouver, B.C. to San Jose, CA

Bike tour from Vancouver, B.C. to San Jose, CA




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AT#75 - Authors of "Europe From a Backpack"

Authors of "Europe From a Backpack"




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AT#123 - Pauline Frommer on Budget Travel

Pauline Frommer on Budget Travel




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AT#161 - Travel to Transylvania in Romania

The Amateur Traveler talks to Shawn about his trip to Transylvania in Romania. We talk, of course, about Vlad III the Impaler (Dracula) but also about the green rolling hills, walled towns, castles and people of this beautiful country.




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AT#219 - Budget Travel Tips from Pauline Frommer

The Amateur Traveler talks to Pauline Frommer again about tips for budget travel. We talk about booking tours and alternative places to stay instead of hotels. We talk about which travel destinations are inexpensive now and which ones have hidden fees. Learn where a travel expert takes her family on vacation.

Pauline Frommer’s London and the second edition of Pauline Frommer’s New York City were named “Best Guidebook of the Year” by the North American Travel Journalists Association (2007 and 2008, respectively).

News

Free aiport wi-fi
Travel Tip Tuesday : American Airlines Announces $8 Blankets
Dirty Hotels
This Week in Travel

Show Notes

Pauline Frommer
Pauline Frommer on Budget Travel – Episode 123
Houe of the Redeemer in NYC
UK Airports face chaos over departure tax rise
Argentina Visa Fee To Hit Tourists Starting Jan 1
ShoreTrips.com
Jamaica – Meet the People
Tlaxcala, Mexico
Oaxaca, Mexico – Felipe the Weaver (part 1) – Video Episode 46
Reciprocity in Brazil Tourist Visa Fees for American and Canadians

Internet Resources

oster.com – hotel reviews

Community

Celeste has Marquesas corrections
David has Marquesas corrections
David, “you break up the monotony”




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AT#227 - Three Weekend Trips From Shanghai, China

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.

News

Spirit Air to experiment with carry-on bag fees
Airlines losing 3000 bags – every hour of every day
Women try to smuggle dead relative onto flight
Paying to use the plane potty?
Ky. Judge Rules in Favor of Online Travel Sites

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?




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AT#242 - Day Trips from Florence, Italy

The Amateur Traveler talks to Italophile Ira Bernstein who returns to the show to talk about day trips in Tuscany that you can take from Florence. We talk about visiting the walled city of Siena and its famous bareback horse race the palio, viewing the many towers of San Gimignano, climbing the leaning tower of Pisa (after you take the obligatory picture of someone holding it up), and walking on the walls of Lucca. Each town has its own character and attractions. Arezzo has a jewelry museum and the home of the “Father of Humanism” Petrarch. Fiesole is a rich enclave, a suburb of Florence with views of the city and a roman theatre. Montepulciano and Montalcino are both known for their wines. Ira talks about some of the events that the locals enjoy like the palios, flea markets and flag throwing competitions. So even if you just get as far out of Florence as Piazzale Michelangelo there are many places to explore in Tuscany.




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AT#288 - Travel to Rome with Andy Steves

The Amateur Traveler talks to Andy Steves about Rome, Italy. Andy talks about practical issues like how to get into and around Rome, how to connect to the Rome of the Roman Empire (the Coloseum, Forum and Circus Maximus, Basilica of Maxentius and Constantine, Pantheon). He also talks about a tour of the Sistine Chapel without all the crowds and not easy to do. Andy also gives us his favorite spots from Renaissance Rome like the Galleria Borghese and how to get under Saint Peter's to the excavation of older Saint Peter's. Follow Andy to places where you can meet modern Romans on your evening passeggiata to Campo di Fiori, Piazza Navona, Trevi Fountain and the Spanish Steps. And then meet one of his favorite Romans who runs a hang out for students near the Pantheon.

Andy is the son of travel author and tour guide operator Rick Steves and is following in his father's footsteps running weekend tours for students studying in Europe.




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AT#295 - Travel to Oklahoma with Robert Reid from Lonely Planet

The Amateur Traveler talks to Robert Reid from Lonely Planet about his home state of Oklahoma. Robert recommends when you are driving through Oklahoma on your great American road trip you get off the interstate and explore for a few days. From the hills and woods of Eastern Oklahoma, to the tall grass prairies, to the oldest mountains in the United States (The Wichita Mountains) Oklahoma has more variety than you might have guessed from the Rodgers and Hammerstein musical of the same name. Even the shape of the state holds clues to its unusual history. It is a state shaped by treaties made and broken with the Native Americans and by slavery and the Compromise of 1850. Its people are influenced by its history, its oil, its tornadoes, and of course its football. Ever a storyteller, Robert talks about African American towns, football upsets, buffalo, songwriters, authors, cowboy poets, onion burgers and Route 66.




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AT#369 - Travel to Bucharest, Romania

Hear about travel to Bucharest as the Amateur Traveler talks to Wandering Earl about visiting and living in that city. Earl calls Bucharest one of the most under-rated cities in all of Europe, certainly eastern Europe.




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AT#443 - Travel to New York City with Pauline Frommer

Hear about travel to New York City as the Amateur Traveler talks to Pauline Frommer about her hometown. Pauline was born in New York City and never moved away. She also just finished the Frommer's Easy Guide to New York City guidebook.




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AT#488 - Travel to Northern Romania

Hear about travel to Northern Romania as the Amateur Traveler talks to Ralph Velasco of photoenrichment.com about the region that he visited leading a recent photo tour.

We talk about the regions of Maramureş and Bukovina, north of Transylvania.




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AT#517 - Travel to the Danube Delta, Romania

Hear about travel to the Danube Delta in Romania as the Amateur Traveler talks to Christian Cummins about traveling to this UNESCO biosphere in Europe.




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Oil from Garbage

As long as we have garbage, we'll never run out of oil, thanks to a technology called thermal depolymerization process (TDP).




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Academic Who Infamously Mocked Barron Trump Gets Censorship Gig from Facebook

A powerful player on Facebook’s new content oversight board infamously mocked Barron Trump during last year’s impeachment hearings, sowing doubt in the social media platform’s promises of unbiased moderation. The selection of Pamela Karlan, a professor at Stanford Law School, was announced Wednesday by Facebook, according to CNBC. Karlan will sit alongside 19 other experts…

The post Academic Who Infamously Mocked Barron Trump Gets Censorship Gig from Facebook appeared first on The Western Journal.




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10-Month-Old Gets Heartwarming Celebration from Hospital Staff After Finishing Chemotherapy

As confetti floated through the air, a baby boy and his family celebrated his final chemotherapy treatment in time to go home before his first birthday. According to KSAZ, young Aaron has been battling a rare form of cancer called acute megakaryoblastic leukemia since he was four months old. Aaron was a patient at Duke…

The post 10-Month-Old Gets Heartwarming Celebration from Hospital Staff After Finishing Chemotherapy appeared first on The Western Journal.




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A Type of Computing: NYTimes Crossword Moves from AWS to Google App Engine




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Report: After Amazon-Whole Foods Deal, Target Plans Move from AWS Cloud




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Great leaders inspire innovation and creativity from within their workforces

Rita J. King, co-director and EVP for business development at Science House, recently conducted a series of interviews with business leaders, exploring the challenges and hurdles companies face in evolving business landscapes. In this interview, King chats with James Jorasch, founding CEO of Science House, about the importance of innovation and how to inspire and […]



  • Future of the Firm
  • Big Systemic Thinking


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Soap promises to make you smell like "Naval Supremacy"

Ironic toxic masculinity is in fashion! The Duke Cannon Naval Supremacy Big Brick of Bar Soap for Men [Amazon] promises that those thusly-soaped will smell of "naval supremacy", "productivity" or other humorously-abstract scents. (More traditionally "manly" odors such as tobacco, leather, burned vegetation, etc. are also available).

The veil of humor is threadbare -- "get clean and smell good without using feminine shower gels and accessories" -- but I'll admit that I do bathe in warm turpentine and it really helps.

UPDATE: Here's a balding treatment called "Lethal Uprising", spotted by Greg Sideyr.

Looking forward to Internecine Violence Toothpaste, Shambolic Venezeulan Coup Ice Cream, and Silently Endure Prison Abuse Hemmorhoid Cream with Aloe Vera. Read the rest




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Roy Horn of Siegfried & Roy dies from coronavirus at 75

Roy Horn of Siegfried & Roy, the duo whose extraordinary magic tricks astonished millions until Horn was critically injured in 2003 by one of the act's famed white tigers, has died. He was 75.




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3 N.Y. children die from syndrome possibly linked to COVID-19

New York Gov. Andrew Cuomo says three children in the state have now died from a possible complication from the coronavirus involving swollen blood vessels and heart problems.




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Sport24.co.za | Cycling's Vuelta a Espana cuts Portugal from itinerary

The Vuelta a Espana organisers have confirmed that a race already rescheduled and shortened would also now cut its foray into neighbouring Portugal from the 2020 itinerary.




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Sport24.co.za | New Bulls chief Rathbone can't wait to learn from Jake

The genial young administrator with a burgeoning reputation chuckles when it's pointed out to him that he can't seem to shake off 'working' for some of South Africa's biggest businessmen.




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Watch Miles from Tomorrowland Online | Season 1 Full Episodes Video Streaming & Torrent Search

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 […]




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Article: Pernod Ricard Anticipates Big Benefits from Display Advertising in 2018

Luis Spencer Freitas, digital marketing director at Pernod Ricard USA, explains what will drive greater innovation in display advertising next year.




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Live Q&A on remote working, working from home, and running a business remotely

In this livesteam, David and I answer audience questions about how to work remotely. At Basecamp we’ve been working remotely for nearly 20 years, so we have a lot of experience to share. This nearly 2-hour video goes into great detail on a wide variety of topics. Highly recommended if you’re trying to figure out… keep reading





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B.C. records 29 new cases, one more death from COVID-19

B.C. recorded 29 more cases of COVID-19 and one more death over the last 24 hours, provincial health officials announced Friday.




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Chicago Inmate Switches Identities While Wearing Mask…Is Released from Jail

The following article, Chicago Inmate Switches Identities While Wearing Mask…Is Released from Jail, was first published on 100PercentFedUp.com.

A Cook County, Chicago inmate, was able to switch identities with another inmate allowing the wrong inmate to be released. How did they carry that off without anyone catching them? The inmate was wearing a mask when he was released, so it wasn’t as easy to identify him. Last Saturday, Quintin Henderson (pictured below), 28, […]

Continue reading: Chicago Inmate Switches Identities While Wearing Mask…Is Released from Jail ...




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Video: Salon Owner Shelley Luther Released from Jail After Obama-Loyalist Judge Sentenced Her to 7 Days

The following article, Video: Salon Owner Shelley Luther Released from Jail After Obama-Loyalist Judge Sentenced Her to 7 Days, was first published on 100PercentFedUp.com.

Salon A La Mode owner Shelley Luther was just released from jail today. The Texas Supreme Court and Texas Governor Greg Abbott both called for her release today (see below). When Luther left jail she was greeted by supporters who yelled “Shelley’s Free!” She thanked all of the new friends she’s made during this difficult […]

Continue reading: Video: Salon Owner Shelley Luther Released from Jail After Obama-Loyalist Judge Sentenced Her to 7 Days ...




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Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut

The following article, Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut, was first published on 100PercentFedUp.com.

When Dallas, Texas salon owner Shelley Luther opened her salon in defiance of the lockdown order in Texas, she was visited numerous times by the local police and then sentenced to 7 days in jail with a fine of $7,000. After public outrage at her punishment, the Texas Supreme Court stepped in to demand her […]

Continue reading: Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut ...




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How to Fight the Economic Fallout From the Coronavirus

4 March 2020

Creon Butler

Research Director, Trade, Investment & New Governance Models: Director, Global Economy and Finance Programme
Finance ministries and central banks have a critical role to play to mitigate the threat Covid-19 poses to the global economy.

2020-03-03-TokyoCV.jpg

A pedestrian wearing a face mask walks past stock prices in Tokyo on 25 February. Photo: Getty Images.

Epidemics, of the size of Covid-19, have huge economic impacts – not just from the costs of managing the health of people, but stopping them, and keeping the economy working. The 10% fall in global stock markets since it became clear that Covid-19 would not be limited to China has boldly highlighted this.

Suppressing the epidemic, but allowing the economy to still function, requires key decisions, in which central banks and finance ministries play a part.

The role of fiscal and monetary authorities in managing an epidemic economy

The scope to use monetary policy to manage the economic impact of Covid-19 is limited. The fact that the underlying cause of the shock is an infectious disease outbreak (rather than a banking crisis, as in 2008-09) and nominal interest rates are currently close to zero in most major advanced economies reduces the effectiveness of monetary policy.

Since 2010, reductions in fiscal deficits mean there is more scope for supportive fiscal action. But even here, high public debt levels and the desire not to underwrite ‘zombie’ companies that may have been sustained by a decade of ultra-low interest rates remain constraints. 

However, outside broad based fiscal and monetary policies there are six ways in which finance ministries and central banks will play a critical role in responding to the crisis.

first crucial role for finance ministries and central banks is in helping provide the best possible economic evaluation of strict containment measures (trying to isolate each potential case) versus managing the epidemic (delaying the spread of the virus, protecting the most vulnerable and treating the sick, while enabling the majority of people to get on with daily life). Given the economic consequences, they must play a full part, alongside health experts, in advising political leaders on this key decision.

Second, if large numbers of staff are required to work from home to manage the epidemic, they have the lead role in doing whatever is necessary to ensure that financial markets – and thus the wider economy – will continue to function smoothly.

Third, they need to ensure adequate funding for the public health response. Steps that can make an enormous difference to the success of containment strategies, such as strengthening surveillance, and guaranteeing the availability of testing kits and protective equipment for front line health workers, must not fail because of a lack of funding. 

Fourth, they have a lead role in designing targeted economic interventions for the wider economy. Some of these are needed immediately to re-enforce and incentivize strict containment strategies, such as ensuring that employees without full or adequate sick leave cover have the financial support to enable them to report and self-isolate when they get sick. 

Other interventions may help improve the resilience of the economy in accommodating moderate ‘social distancing’ measures; for example, by providing assistance to small firms to help them gear up for home working.

Yet others are needed, as a contingency, to safeguard the most vulnerable sectors (such as tourism, retail and transport) in circumstances where there is a prolonged downturn. The latter may include schemes to allow deferral of tax payments by SMEs, or steps to encourage loan extensions and other forms of liquidity support from the banking system, or by moves to underwrite continued provision of business insurance.

Fifth, national economic authorities will need to play their part in combatting ‘fake news’ through providing transparent and high-quality analysis. This includes providing forecasts on the likely economic impact of the virus under different scenarios, but also detailed information on the support and contingency measures they are considering, so they can be improved and refined through feedback. 

Sixth, they will need to ensure that there is generous international support for poor countries, by ensuring the available multilateral support facilities from the international financial institutions and multilateral development banks are adequately funded and fit for purpose. The World Bank has already announced an initial $12 billion financing package, but much more is likely to be needed.

They also need to support coordinated bilateral aid where this is more effective, as well as special measures to support particularly vulnerable groups, for example, in refugee camps and prisons. Given the importance of distributing sophisticated medical equipment and expertise quickly, it is also important that every effort is made to avoid delays due to customs and migration checks.

Managing the future

The response to the immediate crisis will rightly take priority now, but economic authorities must also play their part in ensuring the world finally takes decisive steps to prevent a repeat of Covid-19 in future.

The experience with SARS, H1N1 and Ebola shows that, while some progress is made after each outbreak, this is often not sustained. This epidemic shows that managing diseases is absolutely critical to the long-term health of global economy, and doubly so in circumstances where traditional central bank and finance ministry tools for dealing with major global economic shocks are limited.

Finance ministries and central banks therefore need to push hard within government to ensure sustained long-term funding of research on prevention and strengthening of public health systems. They also need to ensure that the right lessons are drawn by the private sector on making international supply chains more robust.

Critical to the overall success of the economic effort will be effective international coordination. The G20 was established as the premier economic forum for international economic cooperation in 2010, and global health issues have been a substantive part of the G20 agenda since the 2017 Hamburg Summit. At the same time, G7 finance ministers and deputies remain one of the most effective bodies for managing economic crises on a day-to-day basis and should continue this within the framework provided by the G20.

However, to be effective, the US, as current president of the G7, will need to put aside its reservations on multilateral economic cooperation and working with China to provide strong leadership.




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Spectral and photochemical diversity of tandem cysteine cyanobacterial phytochromes [Plant Biology]

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.




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Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3 [Cell Biology]

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.




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Modification of a PE/PPE substrate pair reroutes an Esx substrate pair from the mycobacterial ESX-1 type VII secretion system to the ESX-5 system [Molecular Bases of Disease]

Bacterial type VII secretion systems secrete a wide range of extracellular proteins that play important roles in bacterial viability and in interactions of pathogenic mycobacteria with their hosts. Mycobacterial type VII secretion systems consist of five subtypes, ESX-1–5, and have four substrate classes, namely, Esx, PE, PPE, and Esp proteins. At least some of these substrates are secreted as heterodimers. Each ESX system mediates the secretion of a specific set of Esx, PE, and PPE proteins, raising the question of how these substrates are recognized in a system-specific fashion. For the PE/PPE heterodimers, it has been shown that they interact with their cognate EspG chaperone and that this chaperone determines the designated secretion pathway. However, both structural and pulldown analyses have suggested that EspG cannot interact with the Esx proteins. Therefore, the determining factor for system specificity of the Esx proteins remains unknown. Here, we investigated the secretion specificity of the ESX-1 substrate pair EsxB_1/EsxA_1 in Mycobacterium marinum. Although this substrate pair was hardly secreted when homologously expressed, it was secreted when co-expressed together with the PE35/PPE68_1 pair, indicating that this pair could stimulate secretion of the EsxB_1/EsxA_1 pair. Surprisingly, co-expression of EsxB_1/EsxA_1 with a modified PE35/PPE68_1 version that carried the EspG5 chaperone-binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in redirection and co-secretion of the Esx pair via ESX-5. Our results suggest a secretion model in which PE35/PPE68_1 determines the system-specific secretion of EsxB_1/EsxA_1.




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Zinc promotes liquid-liquid phase separation of tau protein [Protein Structure and Folding]

Tau is a microtubule-associated protein that plays a major role in Alzheimer's disease (AD) and other tauopathies. Recent reports indicate that, in the presence of crowding agents, tau can undergo liquid–liquid phase separation (LLPS), forming highly dynamic liquid droplets. Here, using recombinantly expressed proteins, turbidimetry, fluorescence microscopy imaging, and fluorescence recovery after photobleaching (FRAP) assays, we show that the divalent transition metal zinc strongly promotes this process, shifting the equilibrium phase boundary to lower protein or crowding agent concentrations. We observed no tau LLPS-promoting effect for any other divalent transition metal ions tested, including Mn2+, Fe2+, Co2+, Ni2+, and Cu2+. We also demonstrate that multiple zinc-binding sites on tau are involved in the LLPS-promoting effect and provide insights into the mechanism of this process. Zinc concentration is highly elevated in AD brains, and this metal ion is believed to be an important player in the pathogenesis of this disease. Thus, the present findings bring a new dimension to understanding the relationship between zinc homeostasis and the pathogenic process in AD and related neurodegenerative disorders.