The Amateur Traveler  talks to Richard Graw about his experiences cruising the canals of England in a canal boat (or narrow boat). The canals traverse through tunnels, up staircases of locks and even up over aqueducts.

The Amateur Traveler talks to to Gary Arndt about the 4 micro-states in Europe: Andorra, Liechtenstein, Monaco, San Marino.  "They all have very unique histories and the one thing that they are all very small"

Hear about travel to the Democratic Republic of the Congo (DRC) as the Amateur Traveler talks to Chris and Sasha Rosencranz about their recent trip to this African country. The DRC is located along the south bank of the Congo River. This large country used to be the Belgian Congo. Chris was previously on the Amateur Traveler talking about the Republic of the Congo as well.

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. 

A special live episode of the Amateur Traveler with three guests, Aaron Saunders, Jonathan Souza and Mary Quincy talking about the recent VikingSocial, Viking River Cruise on the Douro River in Portugal.

Hear about travel to Croatia as the Amateur Traveler talks to Jay Ternavan of JaywayTravel.com about this country on the coast of the Adriatic.

Jay says, "for me Croatia has everything you could look for in a travel experience"

Hear about cruising to Cuba as the Amateur Traveler talks again to Dave Grenewetzki about his trip on a ship based People to People trip to Cuba.

Hear about a Baltic Cruise on Viking Ocean as the Amateur Traveler talks to Mary Jo Manzanares from travelingwithmj.com about their recent Viking Homelands cruise on the Viking Sea.

Hear about travel to the countries of Kiribati, Tuvalu and Nauru in Micronesia as the Amateur Traveler talks to Stefan from Rapid Travel Chai about these small difficult to reach island nations. 

Hear about Cruising Southeastern Alaska on Un-Cruise Adventures as the Amateur Traveler goes on a cruise where dressing for dinner and bingo are replaced with kayaking and bushwhacking.

Hear about a western Mediterranean cruise to Spain, Gibraltar, France, Monaco and Italy on Holland America's Westerdam where I just attended a press trip.

Hear about travel to the Island of Crete in Greece as the Amateur Traveler talks to Elizabeth from compassandfork.com about her travels to this special Greek Island.

Hear about travel to the Crystal Coast of North Carolina as the Amateur Traveler talks to Kit Parks from the Active Travel Adventures Podcast about the area.

Hear about travel to The Canal du Midi and Carcassonne in southern France as Chris from the Amateur Traveler talks about his recent luxury hotel barge cruise.

Hear about a cruise on the Danube, Main and Rhine Rivers from Budapest to Amsterdam as the Amateur Traveler talks again to travel writer Mark Baker.

Hear about travel to Virunga National Park as the Amateur Traveler talks to Niall from Ireland about his visit to this stunning national park in the Democratic Republic of the Congo.

If you love to travel and have a few million spare dollars, you can buy a condo on any of several luxury cruise ships and live there year-round, taking your home with you as you sail around the world.

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.

Eleven members of the Secret Service have tested positive for COVID-19, according a new report. Yahoo News reported Friday it has seen Department of Homeland Security documents which show that 11 individuals currently have the virus and that 23 members of the Secret Service have recovered from the disease. Another 60 employees of the agency…

The post Report: Secret Service Discovers Nearly a Dozen Coronavirus Cases in Its Own Ranks appeared first on The Western Journal.

Sen. Ted Cruz was apparently about to get into mullet territory. He hadn’t had a haircut in three months. Things were looking grim for the Texas senator. Thankfully, Shelley Luther is able to do something about that. Luther is both famous and free after a viral clip of her standing up to a judge who…

The post Ted Cruz Stops by Shelly Luther’s Salon for a Trim, ‘True Authenticity’ Leaves Her Sobbing appeared first on The Western Journal.

This past year, I predicted the fall of both Zuck and Trump, not to mention the triumph of cannabis and rationale markets. But in 2019, the sociopaths won – bigly. Damn, was I wrong. One year ago this week, I sat down to write my annual list of ten or so predictions for the coming … Continue reading "Predictions Review: Trump, Zuck Crush My Optimism In 2019"

By easing distancing measures, the Greater Montreal area could experience a substantial increase in the number of deaths per day due to the coronavirus, according to a new document published by the Institut national de santé publique du Québec (INSPQ) in collaboration with experts from Laval University.

What happens when memers meet the subject of their memes? In the case of the BA Test Kitchen meeting the brains behind @meme_appetit, pure gold. Harry Kersh and Will Martin started the accounts when they discovered their shared love of BA videos, and the Instagram and Twitter accounts have since taken off. 

Now with almost 400,000 followers on Instagram, the account has a lot of fans — including some members of the test kitchen. In this video, the BA cooks explain why they love (or dislike) some of the account's memes, whether it's accurate, and whether they even "get it." Watch them react to various memes and Kersh and Martin attempt to explain their reasoning behind them. Read more...

Even with a stellar crisis plan, the COVID-19 pandemic presents a set of challenges unprecedented in our lifetimes. We don’t know what’s going to happen, and we’re dealing with something growing exponentially, creating uncertainty on a global scale. I managed a team of 40 in Singapore during SARS. That crisis was different, hitting Singapore and […]

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 […]

My pal Jake has been taking regular "cigar walks" (as he calls them) here in our lovely island city of Alameda, California. On those walks, he started spotting some creative flyers...

(I saved the best two for last...)

photos by Jake Schaffer, used with permission

Thanks, Susie! Read the rest

Tens of thousands of other crew members have been trapped for weeks aboard dozens of cruise ships around the world -- long after governments and cruise lines negotiated their passengers' disembarkation. Some have gotten ill and died; others have survived but are no longer getting paid.

One day, a teacher entered her classroom and placed a glass jar on the table. She put two large rocks into the jar until no more could fit. She asked the class if the jar was full and they all said, “Yes.” She responded, “Really?” She pulled out a pile of small pebbles, added them […]

The post How to Become Great by Managing Procrastination appeared first on Dumb Little Man.

Technology has come a long way, and cyber protection is the most crucial factor in advancing the future of digital defense. Interestingly enough, cybersecurity was not always an issue in backup and storage; but as technology advances, so do the methods of hackers. Saying this, let’s take a walk down memory lane. The 1900s: Where […]

The post How Backup And Storage Led To Cybercrime appeared first on Dumb Little Man.

Amazon’s share of US ecommerce approaches 40% February 24, 2020 (New York, NY) — Target’s increased focus on building its ecommerce business has been paying off. The big-box retailer, which […]

1.

Nothing wrecks your living room decor quite like a giant, rented hospital bed.

The one my Dad laid in for a couple months in the fall of 1974 was an alarmingly stiff and sturdy affair, the frame of which was forged of impossibly heavy iron, with half a dozen jaggy coats of putty-flesh latex paint doing a shit job of concealing the dings and dents kissed by dozens of clutches of burly rental guys trying to navigate unaccommodating residential doors.

Jammed cattywampus between a teddy-bear brown sectional, an antiqued rococo credenza, and what had until recently been my Father's favorite armchair, the hospital bed left little room for easy socializing, let alone aesthetic speculation. This was a living room where a very ill person would mostly die soon.

The hospital bed's defining feature was the theoretical ease with which the human trunk slumped in its top half could be raised or lowered by turning a shitty little crank at the foot of its lower half. Like the bed itself, the shitty little crank was ugly and obtrusive and hard to live with. Mom and I tripped over the crank a lot.

The theoretically useful but ultimately shitty little crank made the hospital bed look like those old-timey cars we'd see in the bad silent movies they showed down at Shakey's Pizza.

Mom and Dad despised the saltines-and-ketchup style of pizza served at Shakey's. To them, LaRosa's over on Cheviot had way better pizza plus a pretty good jukebox. But, I really liked Shakey's. They gave away cool styrofoam boater hats with a red paper band that said, "Shakey's Pizza Parlor." Which I thought looked smashing. So, they used to take me to Shakey's.

In practice, the hospital bed's shitty little crank functioned mostly as a recalcitrant and pinch-inducing mechanism for eroding my father's dignity.

Dad would lay in the hospital bed that filled our living room while my Mom slowly cranked. He'd try to make jokes. (Dad had always been the funniest person any of his friends knew.) The hospital bed creaked. Mom cranked. Dad's tired upper half would haltingly rise and bob with reluctant help from the bed's upper half. Mom sweated at the crank. Dad laid there and watched. Dad couldn't help. He watched. He was in the hospital bed. Mom did all the cranking. Dad watched. He watched while his wife turned a shitty little iron crank, trying impotently to make her best friend just a tiny bit more comfortable as his body worked to finally finish eating itself. But, he couldn't help out. I think he wanted to help out. But, he couldn't help out.

She couldn't really help my Dad. My Dad couldn't really help her. But they sure tried.

She cranked and cranked.

I was seven. I didn't know how to help anyone.

2.

The last time I saw my Dad, he was in a different hospital bed. That one was a much more functional and aesthetically appropriate unit neatly fitted into an overlit semi-private room in the highly-regarded Jewish Hospital located on E. Galbraith Road. We weren't Jewish. We were just sick.

Frankly, I forget what the crank on the second hospital bed looked like, but I seem to recall that it worked just fine.

This was maybe a week before my Dad died.

From what I can gather, he and my Mom had wanted to time things so that I could be with him as long and as late as possible--but not so late that I'd have to see him in the kind of condition I have to assume he was in during the full week he was too ill for his boy to visit him. Pretty bad condition, I'm guessing.

In the almost forty years since Dad's last week in any hospital bed, my Mom and I haven't talked much about it. If there are things to say about that week, I'm not sure even forty years is long enough to prep for them. I know I'm still not ready. I should ask my Mom if she's ready. She was forty then. Just under half her life ago.

What I do know is my Mom lived by that second hospital bed most every minute of Dad's last week. Just like she'd been by the first hospital bed in her living room for the months before. Only now she was the one sleeping on the wrong bed. There are limits to the physical comforts you can offer a woman who's determined to stay by her husband's second hospital bed until it's time.

But she was there that whole time. Up to the last time my sweet Dad ever said anything to anyone.

As he laid in that second hospital bed, I'm told that the last thing my Dad said to anyone was something he said to my Mom. He told my Mom:

Take care of The Big Guy.

That was me. I was "The Big Guy." My Dad always called me "Big Guy," and I always loved when he said that. It made me feel strong. It made me feel tall. It made me know that my Dad and I were best pals.

I still love knowing I was my Dad's best pal.

3.

I don't specifically remember the day our particular clutch of burly rental guys came out to remove the first hospital bed from our living room. I do remember thinking it was weird how quickly the space filled with huge floral arrangements, covered dishes and casseroles, and a pack of outdoorsy men with giant red hands who were new to sobbing inconsolably in front of each other.

But, that hospital bed had been heavy. Really heavy. And even though the bed's wheels had been thoughtfully nested in plastic casters, the raw tonnage of the iron motherfucker left permanent dents in our ugly, broccoli-green carpeting. Six breadplate-sized dents that were still there a year and a half later on the day my Mom and I moved out.

We didn't need a house that big for just the two of us. Plus, the living room wasn't much fun to hang out in any more.

Way too big. Way too big.

4.

I don't currently have a hospital bed. I have a modest but very comfortable regular bed in a regular bedroom where I sleep with my regular wife. She's my favorite part of the bed.

To my knowledge, our modest but very comfortable bed is not fitted with a shitty little crank. Which is nice for everyone.

And, every single morning at almost exactly 6:00 AM Pacific Time, my three-year-old daughter wakes up, jumps out of her crank-free, regular, big-girl bed, tears out of her regular bedroom, and--even before she gets her hot milk or takes off her pull-up or tells us to turn on Toy Story 2--she dashes into our regular bedroom, runs up to our regular non-hospital bed, and screams, "DAD-dy! DAD-dy! DAD-dy!" until I wake up and say, "G'mornin', Sweet Bug! Did you have nice sleeps?"

Sometimes she tells me whether or not she had nice sleeps. Often as not lately, she tells me to make her hot milk and turn on Toy Story 2. Both of which I'm totally fine with.

Thing is, she screams "DAD-dy!" like the most impossibly great thing in the world has just happened. Every single morning. Right by my bed. Without a crank in sight.

And, you know what? Something impossibly great has happened.

Because an annoying, rambling, disagreeable little man like me gets to have this alarm clock in piggy-patterned footie jammies run up to a regular, crank-less, healthy-Dad, non-hospital bed and make him feel like he's The Greatest Thing in the Universe.

Just like I think she's The Greatest Thing in the Universe.

Just like I thought my Dad was The Greatest Thing in the Universe.

And, although I'm confident that I will always think my daughter is The Greatest Thing in the Universe, I'm also all too aware that this feeling will not always be reciprocated in quite that same way or with quite that same enthusiasm that we both enjoy right now.

She won't always run to my bed in footie jammies.

I'll only get that particularly noisy and personalized wake-up call for a little while. And, I only get a shot at it once a day. At almost exactly 6:00 AM Pacific Time.

Then one day? I won't get it any more. It will be gone.

5.

Many mornings over the past six months or so, at almost exactly 6:00 AM Pacific Time, I was not in my regular bed. I was not even at home. I was sitting in another building, typing bullshit that I hoped would please my book editor. Who, by the way, is awesome.

And, if I noticed what time it was, I'd always wonder whether my daughter had run into our bedroom yet.

I'd wonder whether she had seen my side of the bed empty again. And, when I thought about my empty spot on the bed and how disappointed she'd be to scream "DAD-dy! DAD-dy! DAD-dy!" then see I'm not even there, I'd die a little.

I'd die a little, because as I thought about her, I'd think about my Dad. And as I thought about my Dad, I'd start thinking about hospital beds with cranks--then on to dents, and covered dishes, and rooms full of sobbing outdoorsy guys, and so on.

But, by then it might be 6:10 am Pacific Time. And I didn't have time to think about my family. Not now, right? No, I had to keep working. I had to stay in that other building and keep typing bullshit that I hoped would please my editor. Who is awesome.

So, I'd type and type. I'd crank and crank. I'd try and try. I'd want very much to go home, make hot milk, and watch Toy Story 2. So much, I'd want this.

6.

Anyhow, this has been my on-and-off job for the past two years. I type. And, I try to type things that will help and comfort people, but mostly I try to type things that will please my editor. Who is awesome.

Sometimes I do my job at 6:00 AM Pacific Time. Sometimes I do my job at 5:30 PM or 11:30 AM or really any time in between. Sometimes I do my job while my family goes to birthday parties and holiday dinners and a couple vacations and I don't even know how many (non-Shakey's) pizza nights--all without me. Without Dad.

In fact, a depressing amount of the time--really up until this week--I would do my job until I hadn't the slightest idea what time it was or what bullshit I was typing or what my crank was ever meant to be attached to in the first place.

But, even when my shitty little crank was not attached to anything, I did keep cranking. Because, Dads do their job. It's what they do.

They crank. They crank and crank and crank and crank.

Sometimes the cranking made something special that will be really useful to people who badly need the comfort and help. But, a staggering amount of the time, my cranking has produced joyless and unemotional bullshit that couldn't comfort, help, or please anyone. Especially my editor. Who is awesome. There's no point in doing anything if it doesn't eventually please my editor. Who is awesome.

This has constantly hung over my head. For two fucking years.

But, this has been my job. It's a job I often did late. It's a job I often did poorly. And, it's a job where I often didn't pull my load or live up to even my own expectations and standards. Which is far from my editor's fault.

She's been awesome.

7.

Anyhow, I've tried to do my job. But, I've often failed.

I've sometimes failed to make things that will help and comfort people. And, God knows I've failed to please my editor.

And, worst of all, more often than my heart can bear at 2:34 pm Pacific Time on Friday April 22nd, I know I've failed to be home for several of my daily shot at "DAD-dy! DAD-dy! DAD-dy!"

It's now become unavoidably clear to me that I've been doing each of these things poorly. The job, the making, the pleasing, and, yeah, the being at home. And I can't live with that for another day. So, I've chosen which one has to go. At least in the way it's worked to date. Which is to say not working.

I'll let you guess which.

Because, that? That choosing? That's what my book needs to be about. Not about pleasing people. Not about cranking on bullshit. Not about abandoning your priorities to write about priorities.

My book needs to be about choosing a hard thing and then living with it. Because it's your thing.

But, that part's gone missing for just a little too long now. Certainly not missing from my handsome and very practical rhetoric--it's been missing from my actual life and living. In a quest to make something that has increasingly not felt like my own, I've unintentionally ignored my own counsel to never let your hard work fuck up the good things. Including those regular people. Including, ironically, the real work. Including any good thing the crank is supposed to be attached to.

So, I'm done fucking that up. I'm done cranking. And, I'm ready to make a change.

I'm not sure precisely what that change will look like, but, at the risk of invoking Godwin's Law, I have a pretty good idea that this particular performance of "Edelweiss" you're enjoying right now may immediately be followed by a dramatic chase, a hopeful escape attempt, and only if I'm extremely lucky, maybe an eventual stride over the Alps.

As I'll explain in a minute, it most likely means I don't have My Book Contract any more.

Who knows? We'll have to see.

8.

All I know is tonight's Friday. And, that's Daddy-Daughter Night.

And, my book agent says my editor (who is awesome) will probably cancel My Book Contract if I don't send her something that pleases her…today. Now. By tonight. Theoretically, I guess...uh...this.

See: my agent very helpfully suggested I send my editor a chapter full of "email stuff." My editor really likes "email stuff." And, it was theorized by my agent that sending this "email stuff" might please my book editor just enough that she might not cancel My Book Contract. For now.

Well. If you've made it this far, you, like my editor (who is awesome), will have realized that this is not a chapter of "email stuff."

It's a very long, wooly, histrionic, messy and uncomfortable story about hospital beds, piggy jammies, and styrofoam hats. I seriously doubt it will please my editor. Who is awesome.

So, no, I really hope she doesn't cancel My Book Contract. But, it does occur to me that said contract is the last and only thing my publisher has to intimidate me into doing things I don't want to do. Things I think will harm my book, my integrity, and my life.

Once that threat is made good, the game ends. They can sue me and yell and stuff. Which would suck, but at least no one would be demanding my book have fucking pussy willows on the cover. Which, as I sit here, feels more and more unbearable to me.

In any case, I don't control anything that anyone does. It took a long time for me to really get that.

It's such a funny thing. Threats--like hurricanes and rectal exams--are only scary until they arrive. Once they're over, they're just the basis for funny stories. But, you do nearly always survive them. And, if you didn't survive? It wasn't because of a lack of fear. Like I say, the universe doesn't particularly care whether you're scared.

Oh, well. I like my editor. She's awesome. I hope she doesn't cancel My Book Contract. I hope we keep working together.

But if it goes away today, tomorrow or further on? Well. As a favorite novelist of mine used to say: "So it goes."

I'll figure this out tomorrow. Or Monday. Or later. Tonight is Daddy-Daughter Night. And, no fucking way am I missing two in a row.

9.

Now, as far as My Goddamned Book? Truthfully? Wanna hear the really complicated part?

This is not me quitting the book. No fucking way. This is me doubling down on the book--on my book.

I will finish my book very soon. Not because of (or in spite of) any contract, and not because of (or in spite of) any editor, and certainly not because of (or in spite of) any tacit demand for empty cranking.

I will finish my book because I want to finish it. Because it is very, very important to me to finish it.

But, again, let's be clear-- what I finish will be my book. And, it will be done my way. And, yes--you Back to Work fans knew this one was coming--my book will have my cover that I choose. It will not have fucking pussy willows or desert islands or third-rate kerning. It will be, to quote my editor (who is awesome), "messy."

My book will help and comfort the people that I want to reach. And, yes, much like my editor, my book will be awesome.

I truly hope my book pleases her.

10.

So, there you have it. An article that's clearly not a chapter of "email stuff."

Me? I'm off to prep for "Daddy-Daughter Night."

And, tomorrow morning, unlike last Saturday morning and countless other days before it, at the crack of 6:00 am Pacific Time, I will be available in my regular crankless bed to ask my daughter whether she had nice sleeps. And I will tell her and my regular wife that I think they're the Greatest Things in the Universe.

And, maybe after I make hot milk and watch Woody worry about cowboy camp, I may even think to myself about how proud my funny Dad would be of his pal, The Big Guy. For doing what needed to be done. To be someone special's Dad for as often and as long as he can. Just like he did. Even when it gets hard.

Even when it gets really hard.

Thanks for listening, nerds. You'll hear more when I hear more.

The DML News App offers the best in news reporting.

The post VIDEO: AG Barr criticizes Mueller’s handling of Steele dossier appeared first on Dennis Michael Lynch.

The DML News App offers the best in news reporting.

The post REPORT: Recent documents reveal number of Secret Service agents with COVID-19 appeared first on Dennis Michael Lynch.

The DML News App offers the best in news reporting.

The post REPORT: Governor criticized over highest nursing home death toll appeared first on Dennis Michael Lynch.

Church bells rang out across the city of Barrie on Friday morning to commemorate the anniversary of the Victory in Europe Day on Friday.

While infection rates remain steady across the region, the Simcoe Muskoka District Health Unit is reporting more than half of all 360 cases have now recovered.

The following article, Legal Immigrant in Michigan Sends a Message to MI Gov Whitmer and Media Criticizing Freedom-Loving Protesters, was first published on 100PercentFedUp.com.

The media and even some governors are trying to paint the Americans who are protesting to open businesses up as racists and even Nazis. The Governor of Michigan recently made a derogatory statement about the protesters implying they are racists. Painting a negative picture of the people who want their freedom and businesses demonizes our […]

Continue reading: Legal Immigrant in Michigan Sends a Message to MI Gov Whitmer and Media Criticizing Freedom-Loving Protesters ...

The following article, ‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion, was first published on 100PercentFedUp.com.

Transcripts of House Intelligence Committee interviews have been cleared for release, and Adam Schiff is reportedly in panic mode. Unfortunately for Schiff, top law enforcement and intel officials said they saw no evidence of collusion between the Trump campaign and Russia in the transcripts. Republicans sought and got approval for the release of the transcripts […]

Continue reading: ‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion ...

The following article, Texas Gov Abbott Frees Salon Owner Shelley Luther: “Criminals shouldn’t be released to prevent COVID-19 just to put business owners in their place”, was first published on 100PercentFedUp.com.

Texas Governor Greg Abbott just changed the coronavirus order to free Salon A La Mode owner Shelley Luther from jail. Abbott tweeted out a comment about the poor treatment of the business owner: Throwing Texans in jail whose biz’s shut down through no fault of their own is wrong. I am eliminating jail for violating […]

Continue reading: Texas Gov Abbott Frees Salon Owner Shelley Luther: “Criminals shouldn’t be released to prevent COVID-19 just to put business owners in their place” ...

The following article, Video Scrubbed of Obama-Biden Ambassador To China Praising Their Response to Coronavirus: “I take my hat off to China”, was first published on 100PercentFedUp.com.

During a recent interview on CNN, Obama-Biden ambassador to China (2014-2017) Max Baucus compared standing up to China on the coronavirus to “Hitler in the ’30s.” Baucus has proven himself to be sympathetic to China in recent interviews, where he puts down America and praises the Chinese. The MSNBC video via The Washington Free Beacon […]

Continue reading: Video Scrubbed of Obama-Biden Ambassador To China Praising Their Response to Coronavirus: “I take my hat off to China” ...

The following article, Breaking: Justice Department Dropping Michael Flynn Criminal Case, was first published on 100PercentFedUp.com.

Michael Flynn has finally been exonerated. The Associated Press is reporting exclusively that the Justice Department said it is dropping the criminal case against President Trump’s first national security adviser, Michael Flynn. In court documents being filed Thursday, the Justice Department said it is dropping the case “after a considered review of all the facts […]

Continue reading: Breaking: Justice Department Dropping Michael Flynn Criminal Case ...

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 ...

A beverage company in the U.S. is inviting moms to let out a ‘quaranscream’ this Mother’s Day on a designated ‘zero-judgement venting hotline’ for a chance to win its wine spritzers.

17 June 2019

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.

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.

Mutations in retinaldehyde-binding protein 1 (RLBP1), encoding the visual cycle protein cellular retinaldehyde-binding protein (CRALBP), cause an autosomal recessive form of retinal degeneration. By binding to 11-cis-retinoid, CRALBP augments the isomerase activity of retinoid isomerohydrolase RPE65 (RPE65) and facilitates 11-cis-retinol oxidation to 11-cis-retinal. CRALBP also maintains the 11-cis configuration and protects against unwanted retinaldehyde activity. Studying a sibling pair that is compound heterozygous for mutations in RLBP1/CRALBP, here we expand the phenotype of affected individuals, elucidate a previously unreported phenotype in RLBP1/CRALBP carriers, and demonstrate consistencies between the affected individuals and Rlbp1/Cralbp−/− mice. In the RLBP1/CRALBP-affected individuals, nonrecordable rod-specific electroretinogram traces were recovered after prolonged dark adaptation. In ultrawide-field fundus images, we observed radially arranged puncta typical of RLBP1/CRALBP-associated disease. Spectral domain-optical coherence tomography (SD-OCT) revealed hyperreflective aberrations within photoreceptor-associated bands. In short-wavelength fundus autofluorescence (SW-AF) images, speckled hyperautofluorescence and mottling indicated macular involvement. In both the affected individuals and their asymptomatic carrier parents, reduced SW-AF intensities, measured as quantitative fundus autofluorescence (qAF), indicated chronic impairment in 11-cis-retinal availability and provided information on mutation severity. Hypertransmission of the SD-OCT signal into the choroid together with decreased near-infrared autofluorescence (NIR-AF) provided evidence for retinal pigment epithelial cell (RPE) involvement. In Rlbp1/Cralbp−/− mice, reduced 11-cis-retinal levels, qAF and NIR-AF intensities, and photoreceptor loss were consistent with the clinical presentation of the affected siblings. These findings indicate that RLBP1 mutations are associated with progressive disease involving RPE atrophy and photoreceptor cell degeneration. In asymptomatic carriers, qAF disclosed previously undetected visual cycle deficiency.

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.