Hear about the best of California's state parks as the Amateur Traveler talks to Jeff Ohlfs who has been to all the parks in the state park system.

Hear about travel to Northern Pakistan and the  Karakoram Highway as the Amateur Traveler talks to David Harden from travelwornsatchel.com about his road trip in this remote and beautiful country.

Hear about travel to Tbilisi and the eastern part of the Republic of Georgia as the Amateur Traveler talks to Tommo & Megsy from FoodFunTravel.com who have settled in Georgia.

Newly appointed White House press secretary Kayleigh McEnany continues to impress in her new position working for the White House. Two days after absolutely leveling members of the White House media corps, the 32-year-old former Trump campaign spokeswoman made waves Friday by warning Americans that they, like former National Security Advisor Michael Flynn, could also…

The post New White House Press Sec Issues Dire Warning to Americans About the FBI appeared first on The Western Journal.

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.

An evangelical church network in California will ignore Democratic Gov. Gavin Newsom’s executive prohibitions this month, opening sanctuary doors for communal worship despite the ongoing coronavirus pandemic. According to Fox News, California Church United, representing roughly 3,000 churches and 2.5 million congregants statewide, announced Thursday that it will return to conducting in-person services by Pentecost…

The post Huge Group of California Churches Announces Plan To Defy Governor Newsom’s Order appeared first on The Western Journal.

What one expert called “something out a monster cartoon” has now arrived in the United States. The Asian giant hornet, which can decimate bee colonies and is responsible for 50 deaths a year in Japan, is now in Washington state, according to The New York Times. A new threat reaches the United States: A massive…

The post Giant Asian ‘Murder Hornets’ Spotted in US for First Time appeared first on The Western Journal.

Between having had more than enough of the not-so-great indoors and realizing that the grocery store might not always have meat, Americans are increasingly looking to feed themselves by hunting. “People are thinking about where they get their food and how they get their food,” Land Tawney, president of the advocacy group Backcountry Hunters and…

The post Facing Concerns of Meat Shortages, More Americans Turn to Hunting appeared first on The Western Journal.

“Outbreaks have sparked riots and propelled public-health innovations, prefigured revolutions and redrawn maps.” – The New Yorker, April 2020 “Nothing will be the same.”  That’s the overwhelming takeaway I’ve heard from dozens of conversations I’ve had with C-suite leaders, physicians, policy experts and media professionals these past few weeks.  When it comes to the business … Continue reading "An Open Letter To American Corporations: It’s Good Business (and Smart Marketing) To Support Quality Journalism"

By the time Martin Smith reached Syria this past summer, the war was already in its fifth year, but life in regime-controlled areas was still largely a mystery.

Attorney General Eric Schneiderman has issued a cease-and-desist order to the nation’s two largest daily fantasy sports companies, saying that the betting that takes place on their sites breaks New York's online gambling laws.

TL;DR: You don't have to buy a drum set to learn how to play the drums. Instead, just grab the Senstroke by Redison bluetooth drum kit for $189.95, on sale for 5% off as of May 9.

If you want to learn how to play the drums, then a quality set may cost you upwards of $1,000. Not only is this a hefty price to play for individuals who aren't fully committed to the instrument yet, but their massive size may be impossible to fit inside your space. Or at least your housemates may not appreciate it.

With the Senstroke by Redison Bluetooth Drum Kit and App Bundle, you can practice, play, and record on just about any surface for a much more affordable price — and it'll take up little to no space.  Read more...

In a startling turn for a robot that has long haunted your dreams, Boston Dynamics' Spot has been tasked to encourage healthy behavior. 

According to the Straits Times, the robot "dog" has been assigned to patrol the Bishan-Ang Mo Kio park in Singapore with the express purpose of encouraging social distancing. 

"Let's keep Singapore healthy," sounds a recording from the robot as it trots by two terrified people relaxing on a park bench in the above video. "For your own safety, and those around you, please stand at least one meter apart. Thank you."

Notably, Spot's jaunt is part of a two-week trial that began Friday. The robot will supposedly not collect any personal information on the people it admonishes.  Read more...

I interviewed four business leaders in late 2019 to get their perspectives on the biggest obstacles and opportunities organizations are facing. Craig Lemasters was the president and CEO of Assurant Solutions. Under his leadership, Assurant Solutions doubled in size to $4B, underwent a digital transformation to expand an offering of risk management solutions in the […]

Data Governance sounds like a candidate for the most boring topic in technology: something dreamed up by middle-managers to add friction to data scientists’ lives. The funny thing about governance, though, is that it’s closely related to data discovery. And data discovery is neither dull nor additional friction; it’s an exciting process that enables great […]

A couple of days ago, Thomas Dolby posted this video to Twitter and YouTube of a track called "Corona and the Pirate Twins," a spoof of his 1982 hit, "Europa and the Pirate Twins." The song is credited to Dolby Kids. Thomas included the following note:

"This is what my mischievous offspring have been getting up to during the Lockdown."

Here is the original video for "Europa..."

Bonus track:

And here is Thomas Dolby doing a touching home solo version of his achingly beautiful "Screen Kiss" from 1984's Flat Earth. He did it as a tribute to Matthew Seligman, the celebrated bassist who recently died of COVID-19. Seligman played bass on Dolby's recordings, including Flat Earth, and also played for Bowie, Robyn Hitchcock, Peter Murphy, and countless others. He was also a member of the Soft Boys.

Image: YouTube Read the rest

The Gothamist is reporting the sad news that Gem Spa, the iconic NY corner store that has been a fixture at St. Marks Place and Second Avenue for around 100 years is being forced to shutter its doors and windows for the last time. The Spa has been struggling to keep up with increasing rent prices and COVID-19 has apparently proven to be the final nail in its coffin.

"It’s where Robert Mapplethorpe bought Patti Smith an egg cream on the day they met. It’s on the back cover of the New York Dolls’ 1973 debut (and where, according to lore, Johnny Thunders and others went for post-heroin sugar fixes between sets at CBGB). Before that, it was where Abbie Hoffman gathered Yippies to rain money on the New York Stock Exchange. It’s where Allen Ginsberg, Ted Berrigan, and other neighborhood poets went to pick up the Sunday New York Times on Saturday nights (and which was inevitably commemorated in their poems)."

Read the rest.

Image: Alex Lozupone, CC BY-SA 4.0 Read the rest

Magician Roy Horn, 75, died Thursday after developing symptoms of Covid-19 several days ago. Horn and partner Siegfried Fischbacher ran the most popular stage show in Vegas throughout the 1990s, featuring hundreds of performers, pyrotechnics and a coterie of white tigers at the Mirage hotel. Horn was forced to retire after suffering a stroke before or as a tiger dragged him from the stage by the neck.

TMZ received a statement from Fischbacher:

"Today, the world has lost one of the greats of magic, but I have lost my best friend. From the moment we met, I knew Roy and I, together, would change the world. There could be no Siegfried without Roy, and no Roy without Siegfried."

Siegfried goes on ... "Roy was a fighter his whole life, including during these final days. I give my heartfelt appreciation to the team of doctors, nurses and staff at Mountain View Hospital who worked heroically against this insidious virus that ultimately took Roy's life."

My first visit to the U.S. was a trip to Vegas in 1999. The first thing I remember seeing of America, stepping blearily out of the taxi at the Mirage Hotel after 15 hours in the air, was a colossal fiberglass statue of Siegfried and Roy. God bless America.

Read the rest

Tear down all the Robert E.T. statues and stop celebrating his invasion tactics.

The creator of Full House Without Michelle returns with a documentary on General Robert E.T. [Reid McCarter / AV Club] Read the rest

The "transient bazaar" known as Lost Horizon Night Market is a covert operation. Worlds are imagined and then built inside the blank canvasses of empty box trucks. For the event, all the "proprietors," and their appointed box trucks, convene in an unsanctioned, though discreet, location. This location is disclosed to would-be "shoppers" via text just a few hours before it starts. Word of the market generally spreads rapidly but not publicly, definitely not by social media. If you're lucky enough to hear about it, you should go.

So, Happy Mutants, this is your heads up. Lost Horizon Night Market: Quarantine Edition is happening Saturday, May 9, from 6:59p EST until 11:59p EST, "rain or shine." This one is a little different, as the spaces are virtual, not in actual, physical trucks. I got a sneak peek yesterday of what's been created and can't wait to dive in deeper. Admission is free, though tips are appreciated. RSVP here.

Previously: Secret box truck 'night market' pops up again in NYC Read the rest

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.

Former England opener Alex Hales is confident he has matured as a player and believes he is ready to make a return to international cricket.

Salomon Rondon says he was on his way to joining Manchester United in January only for Dalian Professional to block the move.

Australia's Super Rugby competition is planning for an early July return, a spokesman has said.

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.

Technology is continuously leaving an indelible mark on many conceivable fields and industries, and education hasn’t been left behind either. Today, you no longer need to take admission classes and physically attend all your classes to earn a degree. All that is required of you is a working web connection and an incontestable thirst for […]

The post 9 Online Resources for Effective Learning appeared first on Dumb Little Man.

In one way or another, social learning has been part of our lives for a long time. We spend a large amount of time at work. During this time, we are bound to learn from our colleagues and get a chance to talk on mutual topics of interest. Moreover, social media has given an outlet […]

The post Social Learning as a Way to Foster Productivity in the Workplace appeared first on Dumb Little Man.

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

William Bao Bean, managing director of Chinaccelerator, explains how investments in artificial intelligence and machine learning are helping marketers improve user targeting and return on investment.

The Northern Pudu (Pudu mephistophiles) is the world's smallest deer. This little inhabitant of the Andes Mountains weighs in at only 3 to 6 kg, or 7 to 13 pounds. The Northern Pudu lives and plays across Columbia, Ecuador, and Peru. They prefer to stay in the higher elevations of the Andes Mountain range. Most of them live at least 2000 meters above sea level. The climate here is a temperate rainforest, with a wet winter and arid summer.

What Do They Look Like?

These little deer have a stocky body and slim legs. They average 32 - 35 cm, or 13 - 14 inches tall. They are approximately 85 cm or 33 inches long. They are slightly larger than a small house dog or a large cat. They have a Southern branch of the family that lives in Chili and Argentina. This species is slightly larger. Their fur is thick, stiff and lays close to the body. They range in color from a reddish brown to a darker brown. The males sport backward curving antlers that do not split.

How Do They Survive?

The Pudu is a solitary animal interacting socially only to mate. They are nocturnal by nature and thrive on leaves, shrubs, sprouts, blossoms and bark. They do not eat meat. They are adept at climbing, jumping and sprinting which helps them evade predators. They tend to move slowly and purposefully through the lush climate, utilizing dense vegetation to hide. Predators include owls, foxes, and large wild cats.

How Many Young Do They Have?

Mating season is short, lasting from April to May each year. Once done they return to their solitary existence. The female Pudu carries her young six to seven months. Most mothers have only one baby, but twins do occur with some regularity. Pudu young will stay with their Mommas for between 8 - 12 months before heading out on their own. Most of them have an average lifespan of 8 - 10 years.

Why Are They Endangered?

The Pudu is listed as vulnerable on the ICUN red list. The main causes of death are disease, loss of habitat, and over hunting. The Pudu is prone to become infected with various types of worms such as the round worm and heart worms. The worms multiply rapidly overcoming their small bodies. Loss of habitat has lead to a decline in mating and death from road accidents. Adding to the problem are hunters. The Pudu is eagerly sought due to the skill needed to track and kill them. Conservationist are working to restore and preserve the habitat for these precious little deer.

Basecamp’s newest product HEY has lived on Kubernetes since development first began. While our applications are majestic monoliths, a product like HEY has numerous supporting services that run along-side the main app like our mail pipeline (Postfix and friends), Resque (and Resque Scheduler), and nginx, making Kubernetes a great orchestration option for us. As you… keep reading

On May 16, 2010, at 10:02 AM, "Xx" wrote:

You mentioned you gave a talk at Rutgers about future proofing your passion. Is this available as a podcast? I'd love to listen!

This poor kid emailed me to ask a really simple question. And I went and saddled him with the world's most circuitously long-winded answer. Surprise, surprise.

Hey, Xx,

Thanks for the note, man. No I'm sorry its not up as audio AFAIK.

FWIW, it's a talk I'm asked to do more often lately so I wouldn't be surprised if it turns up sooner or later.

Since you were kind enough to ask, the talk—which comes out super different each time I do it— consists of a discursive mishmash of advice I wish I'd had the ears to hear in the year or five after graduating from college: primarily, that we never end up anywhere near where we'd expected, and that most of us would have been a lot happier a lot faster if we'd realized that we were often obsessing over the wrong things—starting with how much the world should care about our major. ("Liberal Arts," with a concentration in [ugh] "Cultural Studies," thanks.)

The talk started as a way to encourage students to learn enough about what they care about that any temporary derails and side roads wouldn't scare their horses too badly. But, today, I see it as something a lot bigger that's demonstrably useful to anyone who hopes to survive, evolve, and thrive in this insane world.

A handful of bits I'm (obviously) still synthesizing into something notionally cohesive:

My Kingdom for Some Context!

For myself, I wish I'd known the value of developing early expertise in interesting new skills around emerging technologies (rather than just iteratively pseudo-honing the 202-level skills I thought I "understood"). Alongside that, I wish I'd learned to embrace the non-douchier aspects of building awesome human relationships (as against "networking" in the service of landing some straight job that, as with most hungry young people, locked me into a carpeted prison of monkey work at the worst time possible).

Also how I wish I'd paid more attention to events, contexts, relationships, and change that were happening outside my immediate world —rather than becoming, say, the undisputed master of fretting about status, salary, and whether I was "a success" who had "arrived".

Hint: I was not a "success," and I had not, by any stretch, "arrived."

To my mind, "success" in the real world is much more the equivalent of achieving a new personal best; it's not about whether you won the "Springtime in Springfield SunnyD®/Q105™ 5k FunRun for Entitilitus," and got a little ribbon with a gold crest on it.

Truly, pretty much anyone who feels they've "arrived" anyplace is about to learn a) how much more they could be doing outside the narrowness of an often superficial ambition and b) the surprising number of things they had to give away through the opportunity costs and trade-offs that lead up to every theoretical milestone. It's a real goddamned thistle, and it's more than a little depressing.

Do You Still Really Want to be a Fireman?

[N.B.: I really hope you're taking bathroom breaks here, Xx]

Related, I think this is about how being an adult is not only unbelievably complicated in ways that you can't begin to imagine—that it's frequently defined by impossible decisions and non-stop layers of "hypocrisy"—but that there's an invisible but entirely real risk to doggedly chasing the theoretically laudable notion of "following your dream." Especially if it's a dream you first had while sleeping on Star Wars sheets in a racecar bed.

Not because it's a bad idea to want things or to have ambitions. Quite the opposite. More because, for a lot of us, the "dreams" of youth turn out to be half-finished blueprints for wax wings. And not particularly flattering ones at that.

By starting adult life with an autistically explicit "goal" that's never been tested against any kind of real-world experience or reality-in-context, we can paradoxically miss a thousand more useful, lucrative, or organic opportunities that just…what?…pop up. Often these are one-time chances to do amazing and even unique things—opportunities that many of us continue to reject out of hand because it's "not what we do."

It took me a full decade to learn to embrace the unfamiliar gifts that kismet loves to deliver on our busiest and most stressful days, and which gifts might (maybe/maybe not) even end up bringing the real-life, non-racecar-bed, now me a big step closer to something that's 1000 times more interesting than a hollow, ten-year-old caricature of "what I wanna be when I grow up."

Finding Your "Old Butcher"

Also related, it strikes me that the indisputable wealth of information and options that are provided by the web often comes with a harrowing hidden tradeoff. While we can certainly learn a lot on our own and become (what feels like) an instant expert on any topic in an afternoon, we usually do so in the absence of a mentor and outside the context of applying expertise to solve actual problems. In my opinion, a cadet should have to survive more than a few Kobayashi Maru scenarios before he gets to declare himself, "Captain."

Call it a guru, a wizard, an old butcher, or what have you, the mad echo chamber of a young mind often benefits from the dampening influence of an experienced grownup who can help you understand things that raw data, wikipedia entries, and lists of tips and tricks can't and wont ever do.

We benefit from a hand on the back and a gentle voice, reminding us:

• "Try not to obsess over implementation until you really understand the problem," or
• "Worry more about relationships than org charts or follower counts," or
• "Don't quit looking after you've found that first data point," or—my favorite—
• "Spend less time fantasizing about 'success' and way more time making really cool mistakes."

Conversely, though, I think this means that everything we think we know, as well as all the fancy advice that gets thrown around—absolutely including the material you're reading now—is the product of what one person knows and what another person has the ears to hear. For us. For now. For who really knows what. But it is a transaction that takes place in a very specific time and within the bounds of a set of "known" "facts." So, fair warning, doing your own due diligence never hurts.

What's Almost Not Impossible?

[N.B.: I swear to God this ends at some point, Xx]

One big pattern for "future-proofing" your passion? Keep your eyes open and your heart even "opener." And, be more than simply tolerant of the notion of change—sure, take it as read that nothing is ever fixed in place for more than a little while.

But, to the extent that your sanity can bear it, always keep an eye on the corners, the edges, and especially learn to watch for those infinitesimally tiny figures starting to shuffle around near the horizon. Because a lot of the things that seem ridiculously small and inconsequential right now will eventually cast a shadow that people will be chasing for decades. It's just that we're never sure which tiny figure that will turn out to be.

So, yeah. It really is true that no one but you cares about your major. But, trust me: everybody is interested in the person who repeatedly notices the things that are about to stop being impossible.

Be the curious one who soaks in all that "irrelevant" stuff. And, even as you stay heads-down on the "now" projects that keep the lights on, remember that the guy who invented those lights made hundreds of "failed" lightbulbs before fundamentally upending the way we think about time, family, industry, and the role of technology in how we live and work. But, yes, first he "failed" a lot a lot at something which more than a few of his contemporaries thought was pointless in the first place.

Ask: What's out there right now that's about to stop being impossible? Where will it happen first? Who will (most loudly and erroneously) declare it's total bullshit? Who will mostly get it right—but possibly too early? Who will figure out what it means to our grandkids? Who will figure out how to put it in everyone's front pocket for a quarter?

Y'know who? I'll tell you who: practically anybody BUT that guy in the racecar bed who wants to talk about his major.

Important: Merlin's Advice is Only Future-Proof to 10 Meters

A few years back, most watch manufacturers decided to come clean and stop categorically declaring that their timepieces were "waterproof." Instead, today, the more credible vendors admit their product is merely "water-resistant"—and, even then, they'll only guarantee the underwater functionality at so many meters, and for so long, and under thus and such conditions.

Truthfully, the same applies here. Nothing can actually "future-proof" anything. Anyone who claims to know the future is either a madman, a charlatan, or, often as not, both.

Thing is, regardless of the passions (or goals or values or priorities or whatever) that we hope to protect or defend, we'd all do well to remember that it is still ultimately OUR passion that's at stake.

That means we're the only one responsible for seeing that its functional components survive and adapt in a world in which each one of us has just north of zero control.

If we embrace the fact that no one can or should ever care about the health of our passions as much as we do, the practical decisions that help ensure Our Good Thing stays alive can become as "simple" as a handful of proven patterns—work hard, stay awake, fail well, hang with smart people, shed bullshit, say "maybe," focus on action, and always always commit yourself to a bracing daily mixture of all the courage, honesty, and information you need to do something awesome—discover whatever it'll take to keep your nose on the side of the ocean where the fresh air lives. This is huge.

Anything else? Yeah. Drink lots of water, play with your kid every chance you get, and quit Facebook today. No, really, do it.

Thanks again for the note, Xx, and sorry for the novella. I'll ping you if the audio ever turns up. Til then, forget your major, and break a leg!

yr internet pal,
/m

The DML News App offers the best in news reporting.

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The DML News App offers the best in news reporting.

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School bus drivers in the Upper Grand District School Board are transporting school work instead of students.

The Shelburne Retirement Residence has been devastated by an outbreak of COVID-19, with 90 per cent of its residents becoming infected.

As British Columbians digest the implications in the steps the premier announced in reopening the province's economy, some residents have come to the conclusion they’re too much too soon.

The following article, BREAKING: CBS News Allegedly Staged Fake COVID19 Testing In MI…Makes Dem Gov Whitmer Look Like She’s Doing More To Help Citizens Than Fed Government [VIDEO], was first published on 100PercentFedUp.com.

Project Veritas founder James O’Keefe has done it again. He’s uncovered yet another deceitful piece of coverage on the Wuhan coronavirus pandemic in America by CBS News. O’Keefe begins his interview with a man whose identity is being hidden, “You’re telling me—you’re 100% certain, that CBS News, CBS News Corporation national—staged a fake event. They […]

Continue reading: BREAKING: CBS News Allegedly Staged Fake COVID19 Testing In MI…Makes Dem Gov Whitmer Look Like She’s Doing More To Help Citizens Than Fed Government [VIDEO] ...

The following article, BREAKING: Sen Marsha Blackburn Introduces Stop COVID Act…Allowing US Citizens To Sue Communist China For Damage They’ve Inflicted On Our Nation, was first published on 100PercentFedUp.com.

Yesterday, Senator Marsha Blackburn (R-TN), along with Senator Martha McSally (R-AZ) introduced the Stop COVID Act, giving Americans the ability to sue Communist China for the damage they’ve inflicted on our nation. Senator Blackburn appeared on Fox News with host Judge Jeanine where she explained the act to Jeanine Pirro. Blackburn told the Fox News […]

Continue reading: BREAKING: Sen Marsha Blackburn Introduces Stop COVID Act…Allowing US Citizens To Sue Communist China For Damage They’ve Inflicted On Our Nation ...

The following article, BREAKING: MI Lawmakers File Lawsuit Challenging Governor’s “Improper” and “Invalid” Emergency Orders: “We’ve attempted to partner with our governor, but she’s rejected”, was first published on 100PercentFedUp.com.

In addition to crushing Michigan's economy, the governor's reckless, one-size-fits-all executive orders are harming an untold number of Michigan citizens.

Continue reading: BREAKING: MI Lawmakers File Lawsuit Challenging Governor’s “Improper” and “Invalid” Emergency Orders: “We’ve attempted to partner with our governor, but she’s rejected” ...

The following article, Attorney for Jailed Dallas Salon Owner Shelley Luther Slams Obama Loyalist Judge as a “Tiny Tyrant”, was first published on 100PercentFedUp.com.

Warren Norred, attorney for Shelley Luther, joined Tucker Carlson to discuss the decision by an Obama loyalist Texas judge to jail his client for reopening her salon during the COVID-19 pandemic. Norred said the judge has exposed himself for the “tiny tyrant” that he is. The judge jailed Luther and even fined her $7,000. Texas […]

Continue reading: Attorney for Jailed Dallas Salon Owner Shelley Luther Slams Obama Loyalist Judge as a “Tiny Tyrant” ...

The following article, MSNBC’s Brian Williams Chuckles With Dem Strategist as He Gloats, Mocks Trump About Tragic Downturn in Economy: “They were going to lose before this hit. They’re just going to lose worse now”, was first published on 100PercentFedUp.com.

James Carville spoke out before the coronavirus crisis to say that there is no way  Joe Biden has a chance at beating President Trump in the 2020 election. Well, He’s singing a different tune now at the expense of Americans suffering through this horrible pandemic and economic crisis. James Carvill is a Democratic strategist who […]

Continue reading: MSNBC’s Brian Williams Chuckles With Dem Strategist as He Gloats, Mocks Trump About Tragic Downturn in Economy: “They were going to lose before this hit. They’re just going to lose worse now” ...

The following article, BREAKING: Michigan’s Radical Governor Extends Lockdown AGAIN…Only One Day After Church Leaders and MI Lawmakers File Suit Against Her, was first published on 100PercentFedUp.com.

Michigan was the first state to see protests against draconian lockdown measures by an overreaching governor. On April 15, the Michigan Conservative Coalition organized an in-vehicle protest in Lansing, MI that drew an estimated 15,000 vehicles. Since that time, several protests by Michigan workers who are being devastated by the one-size-fits-all shut down of the […]

Continue reading: BREAKING: Michigan’s Radical Governor Extends Lockdown AGAIN…Only One Day After Church Leaders and MI Lawmakers File Suit Against Her ...

The provincial government has announced it will support child care centres that have been closed since March with their fixed operating costs as the fight against COVID-19 continues.

Environment Canada has issued a special weather statement for the southwestern area of Manitoba.

The empty space next to Winnipeg City Hall that once housed restaurants could be turned into a place to help exploited women.

The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC.

Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.

Invitation Only Research Event

Event participants

Ali Farhan Hamid, Governor of Anbar Province
Chair: Dr Renad Mansour, Senior Research Fellow, Middle East and North Africa Programme, Chatham House