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Supermarket magnate buys Palm Beach condo for $11M
Seller bought two units last year, including this one for $9.5M
A rendering of Via Flagler by the Breakers, and the project site
The vice chairman of a supermarket company paid $10.8 million for a unit at Via Flagler by the Breakers in Palm Beach.
The Nordlingen Trust and the Redmond Trust, both linked to Read S. MacGregor Jr., bought unit 3 from TAU-MID Partnership LLP and Eye-Man LP, both controlled by Stephen F. Sullivan, according to records. Martim De Arantes-Oliveira is named as a special trustee of the latter two trusts.
MacGregor is the nonexecutive vice chairman of Grocery Outlet, an Emeryville, California-based discount supermarket chain that issued an initial public offering last year. It has 350 stores in California, Washington, Oregon, Pennsylvania, Idaho and Nevada, according to its website. MacGregor's grandfather, Jim Read, founded the company in 1946.
Records show Sullivan, a Massachusetts ophthalmologist, bought the condo for $9.5 million, last year, along with another unit for $10.5 million.
In the latest sale, Premier Estate Properties listed the unit, while Sotheby's International Realty represented the buyer. The recently built condo was listed in July for $12.95 million.
The 5,475-square-foot unit has four bedrooms, five-and-a-half bathrooms and a one-bedroom guest residence.
Via Flagler by The Breakers is a mixed-use development in Palm Beach. Last year, The Breakers paid the Frisbie Group $20 million for a portion of the development. The Frisbie Group still holds control of six condos on the second floor.
In May, Cody and Kristin Crowell bought unit 5 at Via Flagler for $7 million. Cody Crowell is the managing director of construction and asset management at Frisbie Group.
Todd Glaser, partners close on Palm Beach home across from ocean for $13M
Payday lender CEO buys Palm Beach house for $26M
Cash king sells waterfront Palm Beach home for $27M
Must be a gem: Luxury jewelry designer Judith Ripka sells Palm Beach home for $13M
Atlanta real estate investor sells waterfront Palm Beach house for $18M
South Florida's biggest residential sales of 2020


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Lexus' latest trademarks: RC 300, a reborn non-hybrid IS 300 and more…
Published by Joaquín Ruhi on June 8, 2015
In the course of researching and writing our previous Kaizen Factor story on recent Toyota and Scion trademark filings, we also stumbled upon a number of new trademarks surely earmarked for the Lexus brand. Most of these are simply a matter of United States Patent and Trademark Office filings for trademarks previously registered in Europe or Australia. A couple of new and unexpected surprises, however, turned up. On 21 October 2014, Toyota filed U.S. trademark application number 86429787 for RC 300. Almost 6 months later, on 10 April 2015, a parallel U.S. trademark application number 86593239 appeared for IS 300. That's just plain IS 300, no "h", so Lexus has not decided to bring over the IS hybrid to North America. To date, no new corresponding GS 300 application has turned up, but we'll note that an old one for that trademark (filed on 5 December 1991 and registered on 14 December 1993 bearing serial number 74227417) is still described as "live" or active.
Those "300" trademarks seemingly are part of a broader engine downsizing trend within Lexus, parent Toyota and the automotive industry as a whole. A series of Toyota/Lexus "200t" and "500h" trademarks certainly bear this out (more on those in a bit), but perhaps more relevant to these "300" applications is the new, 3rd-generation Toyota Tacoma pickup truck. Officially unveiled on 12 January 2015 at the Detroit Auto Show, its official news release trumpeted
…an all-new, segment-first 3.5-liter Atkinson cycle V6 equipped with Toyota's D-4S technology, featuring both direct and port fuel injection.
as did Toyota Group Vice President and General Manager Bill Fay's presentation there. But is that V6 really all-new, as in a new engine family, or simply the latest evolution of the decade-plus old GR V6 engine family? An April 2015 "Toyota/Scion tentative 2016 Dealer Model Reference page reveals a 7GR engine code for 2016 V6 Tacomas, the smoking gun that reveals the continuation of the current GR V6 family.
But what is the rest of the engine code? Historically, a Toyota engine code alphanumeric prefix (such as the 7GR under discussion) is followed by a dash and 2 or 3 letters denoting the most salient characteristics of the engine. This used to be a fairly predictable game, but the mushrooming of China-specific engine codes (even though they appear to be fairly similar to other older non-Chinese versions of the same engine), different types of fuel injection (port only, direct only or dual direct + port), Atkinson-to-Otto cycle capability, occasional maximum fuel efficiency K designations and inexplicable gaps and jumps in prefix numbers within some engine families currently make this guessing game a very inexact science where the odds are stacked against pundits like yours truly. Case in point: when word came in late September 2012 of a future 2-liter turbo version of the AR 4-cylinder engine, yours truly reckoned it would bear a 3AR-FTE or 3AR-GTE engine code. Instead, the world premiere of the Lexus NX 200t at the April 2014 Beijing Auto Show revealed an 8AR-FTS engine code.
Toyota has been a bit inconsistent on how it does or doesn't trumpet Atkinson-to-Otto cycle capability in its engine codes. Our previous Kaizen Factor story touches upon the NR 4-cylinder engine family, where the 1329cc 1NR-FE engine, upon being upgraded with Atkinson-to-Otto cycle capability, electric VVT-iE and intake port shape optimized for strong vertical tumble flow received a new 1NR-FKE engine code. On the other hand, when the Lexus IS F's 2UR-GSE 5-liter V8 received similar upgrades for its RC F and GS F applications (along with a healthy power boost from 416 hp and 371 lb/ft of torque to 467 hp and 389 lb/ft of torque), the engine code remained unchanged. Then we have the case of the latest addition to the AR 4-cylinder engine: the 6AR-FSE. As described by Malaysia's paultan.org in its report on the 2015 Toyota Camry mid-life refresh, this is essentially a naturally-aspirated version of the Lexus NX 200t engine that nonetheless includes D-4S direct + port injection, Atkinson-to-Otto cycle capability and electric VVT-iE. It is not altogether clear whether this is the powerplant for the upcoming Lexus ES 200 and NX 200 models for Russia, China and other Asian markets, or if they use the simpler, less sophisticated 3ZR-FAE from the European Toyota RAV4.
Back to North America, and the Tacoma. Based on the above, we predict a 7GR-FSE engine code for the newest Toyota truck V6. Given that the 7GR-FSE is essentially the Lexus IS 350 / GS 350 / RC 350's 2GR-FSE 3.5-liter V6 plus Atkinson-to-Otto cycle capability, electric VVT-iE and other enhancements, we're going to further predict that the old 3GR-FSE 3-liter V6 from the 2006 GS 300 will receive Atkinson-to-Otto cycle capability plus electric VVT-iE, a new 8GR-FSE engine code and replace the current 2GR-FSE 3.5-liter V6 to create the just-trademarked RC 300 and IS 300 and GS 300 badge revivals. Performance figures for the new 8GR-FSE are anybody's guess at this point, but if we note that the dual cycle + VVTiE enhancements to the 2UR-GSE 5-liter V8 produced a gain of 51 hp and 18 lb/ft of torque, applying those figures to the old 3GR-FSE 3-liter V6's numbers bring us to 303 hp and 249 lb/ft of torque. In other words, roughly similar horsepower figures (but notably less torque) versus the current 2GR 3.5. Let's not be needlessly pessimistic, though, as this may be mitigated by the extra gear ratios on today's automatic transmissions and possible greater-than-noted performance gains from the dual cycle + VVTiE enhancements (it is widely believed that the newer 2UR-GSE 5-liter V8's true performance potential was curtailed by the decision to avoid the U.S. EPA gas guzzler tax, whereas a 3-liter V6 has more leeway in that regard).
This is hardly the end of the current Lexus new trademarks discussion, for the spate of engine downsizing news also brings us
LS 500h: from Europe to America (or vice versa?)
On 26 May 2015, Jason Siu of AutoGuide first reported on an LS 500h trademark filing in Europe. But, as Kevin Watts of the Lexus Enthusiast brought to our attention, the actual OHIM (Office for Harmonization in the Internal Market) filing was done 4 days earlier, on May 22. That same day, Toyota filed a U.S. trademark for LS 500h with Serial Number 86638889. And what, exactly, does an LS 500h entail? We'll repeat some of our thoughts from last year's report on the LC 500h trademark:
…a 500h implies a 4-liter V6 with the performance of a 5-liter V8…there is, in fact, already a 4-liter V6 in Toyota's repertoire: the 1GR-FE, a truck engine which launched the GR V6 engine family back in 2003…
The 1GR-FE 4-liter V6 is essentially the 2GR-FE 3.5-liter V6 from Lexus' ES 350 and RX 350 (and a plethora of Toyotas) with its stroke increased from 83mm to 95mm (both engines share a 94mm bore)…
A range-topping Lexus 2+2 hybrid sports car with a price tag likely to nudge into low 6-figure pricing in U.S. dollars, however, could hardly be expected to use a straight workhorse truck engine. Beyond more car-like higher horsepower numbers and a more 2GR-like valve lifter system, we would expect a full-on upgrade to dual direct + port injection and Atkinson cycle functionality as on the GS 450 Hybrid's 2GR-FXE, thus creating a 1GR-FXE 4-liter V6 plus electric motors powertrain. Guesstimating such a system's power output is not a task yours truly is even willing to speculate on, but bear in mind that the one specification Lexus has released for the LF-LC Hybrid concept is a 500 hp figure…
Kevin Watts' of the Lexus Enthusiast's other possible suggestion that "the next-generation hybrid system generates the equivalent of 1.5-litre of (extra) displacement and the engine remains as a 3.5L V6 engine" is certainly a viable scenario that cannot be discarded.
But AutoGuide's Jason Siu makes another intriguing suggestion:
There's also the unlikely possibility that Lexus is revamping its naming convention for its hybrid models to represent just the powerplant under the hood, meaning the LS600h would just become the LS500h.
Hmm…in a day and age when Mercedes-Benz and BMW are using the flimsy excuse of turbocharging to justify "badge inflation" that sees 2-liter engines as _28 or 300, 3-liter engines as _35 or 400, 4.4-liters as _50 and 4.7-liters as 550, it would be quite refreshing to see Lexus' clear-cut honesty with its gasoline engine badging extend to its gasoline-electric hybrids. This would, of course, entail a future Wal-Martesque rollback of the marque's hybrid badging, with GS and RX 450h models becoming 350h; IS, ES and GS 300h models becoming 250h; and a lineup that would start with a CT 180h.
In America, a trio of 200t trademarks
Reports of the RC 200t trademark have centered on an Australian filing on 12 August 2013, but, in fact, the U.S. filing was carried out 3 days earlier, on August 9, with trademark #86033759.
The GS 200t trademark filing story also publicly centered on the land Down Under, with an 11 September 2013 filing date. That same day, Lexus parent Toyota was also issued trademark #86061565 in the United States for GS 200t.
Most pundits regard a Lexus IS 200t to replace the IS 250 as a fait accompli in North America, yet the discussion was framed in terms of Australian and European trademark filings on 23 May 2014. It turns out that is also the date for the U.S. filing of IS 200t, with serial number 86290354.
We have not, however, found a U.S. equivalent for the fourth "200t" trademark filed in Australia: RX 200t.
TX: Seemingly the badge of choice for Lexus' 5th crossover/SUV line
As Lexus sought to grow its crossover and SUV lines from RX, GX and LX, it trademarked and then discarded VX (most closely associated with performance models from GM's UK Vauxhall outpost) and JX (snapped up by Nissan for its Pathfinder-based Infiniti JX35 before morphing into the QX60) trademarks. On 20 October 2009, Lexus filed for a TX trademark, which we predicted would grace the long-rumored Toyota RAV4-based, sub-Lexus RX crossover. Other pundits predicted a CX badge more closely associated with old Citroëns and current Mazda crossovers (and one that Toyota never trademarked). It turns out we were all wrong, as Lexus ultimately went with NX instead. Yet, the TX trademark for Toyota/Lexus remains very much live and active, so the predictions have now shifted to TX as the prefix for a new 3-row crossover line – essentially a stretched RX.
Again, a caveat
As we did in our previous story, we remind you that registration of a trademark is not a guarantee that a model bearing that name will reach production. Besides the aforementioned VX and JX, other Lexus-centric badges that have died unused include CT 300h, CT 400h (we're particularly bummed out about those two), IS 300C, RX 440h, LX 520, LX 550, LX 590, LX 600 and JX 470.
Published inBeijing Motor ShowCTESFGSHybridInformed SpeculationISIS FLCLexusLSLXNewsNXRCRC FRXRX 450hToyotaTrademark filings
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Up Front by Emma Hart
1:49PM Oct 20, 2008 • Read Post
Up Front: A Word From the Ministry for Learning People Things
First ←Older Page 1 … 3 4 5 6 7 Newer→ Last
81stcolumn, 00:30 Oct 22, 2008
There are few things more likely to guarantee disaster than me and a Physics exam or a job interview.....I have yet to combine the two
My ahem...O level physics exam was characterised by a series of notable events:
i) Beefy Botham beating the heck out of the Aussies yeah !
ii) Me being collected from the pub on my birthday to do a physics practical - cue images of drunk me trying to do some type of calorimetry lab; water, thermometers, drunk 81st, oh dear. Looked like a swimming lesson instead.
iii) Later that year, my being carpeted for flippancy in the written paper: In response to a question about the relationship between image size and the position of convex lenses I came out with the apparently objectionable "Gets bigger, gets smaller, gets happy....."
I got a B.....
In that Shakespeare, Lord of the Flies etc have been written about a zillion times and they know it inside out, appropriate quotes and all so it's way easier to mark? I imagine that if you haven't seen a movie/read a book and only marking an essay on it for the first time (or even the first 100 times) it would take a heck of a lot longer.
As the current semester closes I await with dread for the 200 or so lab reports I will end up marking, as the days go by I quietly lose the will to live. If I were a vain man, I suspect I would love to see my notes so gloriously reproduced repeatedly. As it was, last years highlight was a report written by someone who clearly had not attended the labs but had heard others talk about them. There followed a magnificent recombinant tale of two otherwise unrelated practical sessions. The candidate very nearly passed if only for the sheer imagination applied to the graphs provided in the report.
Nawthshaw • Since Nov 2006 • 790 posts Report Reply
Amy Gale, 03:35 Oct 22, 2008
By a strange English-exam coincidence, I noticed in last week's Time Out New York that there is a current production of A Man For All Seasons. Which apparently is being staged without the Common Man character.
Part of me wants to tear out the review and mail it to my high school English teacher just to torment her (or possibly give her something to torment the current students with, if they still study it these days).
Another part is just baffled. What happened? Did the building inspector come and insist that a fourth wall was necessary under the earthquake code?
tha Ith • Since May 2007 • 471 posts Report Reply
Craig Ranapia, 07:33 Oct 22, 2008
And while we're at it (men with luv-er-ly voices, that is), Jeremy Irons.
Though I know one or two women who found him a damn less yummy after seeing David Cronenberg's __Dead Ringers__ -- in which he played identical twin gynecologists who have **issues** involving (this being Cronenberg after all) sex, drugs, psychic dissolution, and more body horror than you could shake a speculum at.
A bloody good film -- though the worse date movie imaginable -- but I guess nobody should be surprised this is the film he won an Oscar for:
"You're a very strange man."
"You have no idea..."
Brrr... __Reversal of Fortune__ is well-worth seeking out, because it ends up being (to my surprise) unexpectedly moving as an ambiguous comedy of very bad manners indeed.
North Shore, Auckland • Since Nov 2006 • 12370 posts Report Reply
andrew llewellyn, 08:18 Oct 22, 2008
Never could abide Shakespeare - except when someone with a gorgeous voice and impeccable delivery is doing the talking.
As part of Shakespearean lit, we were treated to a screening of the highly regarded Russian version of Hamlet
As the film started, it became clear that the print we were watching was without subtitles. I moved from the front of the theatre to the back. The very scary Fr McKay asked me what I was doing. I said "I'm getting closer to the exit."
And really, while I endured 45 minutes or so, and many in the class stayed to the bitter end, I couldn't help questioning the use of seeing Hamlet in Russian to teach us the richness of the play, couldn't they find a silent version or something?
Since Nov 2006 • 2075 posts Report Reply
Well, if you wanted to go down that route I know a teacher who twinned King Lear with Akira Kurosawa's __Ran__, and Macbeth with the same director's __Kumonosu-jō (Throne of Blood)__. They're both rather loose adaptations, but intensely cinematic and energetic (and bloody) enough to hold the attention of a class of teenage boys.
And if you're interested, Kurosawa also made fascinating adaptations of Dostoevsky's The Idiot and Gorky's The Lower Depths.
giovanni tiso, 08:48 Oct 22, 2008
I couldn't help questioning the use of seeing Hamlet in Russian to teach us the richness of the play, couldn't they find a silent version or something?
There are plenty of those of course, but what's the difference between a silent version and a version in a language you don't speak? Except with sound you could at least enjoy the music of the words and the rather splendid soundtrack. It isn't the best Hamlet I've seen - that would be Olivier's, if you subtracted Olivier's own uber-narcissistic acting - but it beats the crap out of, let's say, Notting Hill.
Wellington • Since Jun 2007 • 7473 posts Report Reply
It isn't the best Hamlet I've seen - that would be Olivier's, if you subtracted Olivier's own uber-narcissistic acting
You should try Olivier's __Othello__ -- that masterpiece of bootblack camp. (Though Maggie Smith's Desdemona is a reminder that she wasn't always the go to dame for period battle axes of a certain age.) I think the kindest thing you can say about that particular performance is *cough* it hasn't dated well.
And if you're interested, Kurosawa also
Yep, seen 'em all. :) (except The Hidden Fortress, which was remade as Star Wars (for real), I have it on DVD to get to sometime soon)
There are plenty of those of course, but what's the difference between a silent version and a version in a language you don't speak?
Pacing mostly. And this reminds me... I have actually seen a silent version in which Hamlet was a woman (possibly swedish, I can't find a link). That was pretty good.
I have actually seen a silent version in which Hamlet was a woman (possibly swedish, I can't find a link)
Sarah Bernhardt, possibly?
Joe Wylie, 09:14 Oct 22, 2008
You should try Olivier's Othello -- that masterpiece of bootblack camp. . . I think the kindest thing you can say about that particular performance is *cough* it hasn't dated well.
Maybe it's Olivier's kaftan and oversized tacky stage-bling, but it's a bit spooky how much this overhyped 60s turkey resembles - visually, anyway - a blaxploitation flick from the following decade. Give it a crime-jazz Curtis Mayfield-style soundtrack and it might be watchable again.
flat earth • Since Jan 2007 • 4591 posts Report Reply
No (that was only 2 minutes long & had sound).
This one
Though Maggie Smith's Desdemona...
Argh! I never made the connection that it was that Maggie Smith.
I know what you mean - I still can't get my head around the idea that Judi Dench was the original West End Sally Bowles in Cabaret. I don't know about you, but I find it hard to imagine Keira Knightley in 2048 playing Lady Bracknell or Lady Catherine De Bough in another (holographic?) version of Pride and Prejudice.
oh yes
Mind you, on this sort of thing, I recall being amused that in Polanski's MacBeth, Doyle from The Professionals played Banquo.
Mmmmm.... Francesca Annis
Kyle Matthews, 10:16 Oct 22, 2008
Yes, indeed. And Alan Rickman.
And now we're heading to a list of Die Hard bad guys.
Emma Hart, 10:21 Oct 22, 2008
Isn't it odd how the Die Hard movies also suffered from the even-odd problem of the Star Trek franchise?
I'd recommend fans of Jeremy Irons avoid his craptacular performance in Dungeons and Dragons.
This thread makes me think we should have a nerdy Public Address book club. There seems to be a common enough core of interest (if Ian Banks is a decent touchstone), and if we can all have civil discussions about politics, why not about books?
I'm very much in favour of the community here manifesting on relevant social platforms -- and also greatly in favour of me not doing it all.
I do belong to a 'file all your books here' site with discussion boards but I haven't been there for ages. I'll have to see if I can track down the link.
Or, y'know, make one. "All your books are belong to us".
Christchurch • Since Nov 2006 • 4650 posts Report Reply
Danielle, 10:40 Oct 22, 2008
Judi Dench was the original West End Sally Bowles in Cabaret
<squeeeeak> Really?? Oh, I must do more research about the various stage versions. Issyvoo!
My love for that film is so immense. Baz Luhrmann, take some notes on 'divine decadence' in musical form from Mr Fosse, and get back to me.
(Oh, also, speaking of pop-cultural things that are hard to fathom: Bob Fosse was one of the backup dancers in the film version of Kiss Me Kate, wasn't he? In pastel tights?)
Charo World. Cuchi-cuchi!… • Since Nov 2006 • 3828 posts Report Reply
B Jones, 10:46 Oct 22, 2008
I always thought Mr Irons would have made a much better Aragorn than Viggo. In thinking that, I totally forgot until this minute he also costarred with Liv Tyler in Stealing Beauty. That would have been a tad creepy.
He plays Vetinari competently in the otherwise awful Colour of Magic tv adaptation. It amazed me watching that how a really good cast could ruin good material through such rotten pacing and directing.
Wellington • Since Nov 2006 • 976 posts Report Reply
Thank you for the opening, Emma.
Karl Urban looks pensive and/or awe-struck
Karl Urban can't decide whether to shell out for the extended warranty on the new IPod.
Zachary Quinto has a violent allergic reaction to toxic levels of Natural Glow
Erica Banna contemplates his future as rough trade gay geek icon
Zoe Saldana wonders who thought a mini-skirt and go-go boots were practical for a starship
Josh Addison, 10:54 Oct 22, 2008
Ah, that was a glorious performance. Some friends and I once devised a scale of scenery-chewingness - it went some like:
1 Jeremy Irons in__ D&D__ = 10 Nick Nolte in Hulk = 100 John Travolta in Battlefield Earth
As far as majestic voices go, it was Tom Baker who apparently claimed "I can make whippet shit sound like The Old Testament!"
Onehunga, Auckland • Since Nov 2006 • 298 posts Report Reply
Simon Pegg as Scotty! Worth seeing just for that.
Looks appropriately awful though. Hullo bad 1960s Star Trek uniforms :)
Nah. They always try to get you with the alluring casting, like Carell as the titular hero in the awful, awful Get Smart. Wake me up when they cast Pegg as Hamlet. Or Lady Macbeth.
Yes he was - and starting as he meant to go on, he choreographed the utterly sublime 'From This Moment On':
The funny thing is... Luhrmann was pitched 'Chicago' by Miramax all the way back in '94, as his second film. He passed, reportedly saying that he felt Fosse's original production of the show was intimidatingly perfect. (This was the year before the revival that's still running on Broadway.)
Well, I'm ashamed to admit this but J.J. Abrams didn't do a half-bad job with Mission: Impossible 3, and perverse as it may sound it might just be an advantage that Abrams isn't a hard core Trekkie, and can get some critical distance on the more neutoric fanboy nuances. Yes, the usual suspects are screaming bloody murder, but they're same kind of people who trashed the sublime re-boot of Battlestar Galactica because "Starbuck's a man, MooreRon" blah blah blah. Russell 'Queer as Folk' Davies is going to be running Doctor Who! It's the end of the multiverse! Who give a flying fuck at a black hole what these nuts think?
OK, fuck *all* y'all (:)), because TOS is clearly the best series by a long, long way, and I include the uniforms in that assessment. Beatle boots on everyone! And Shatner in a gold skivvy with a girdle *totally* beats Shatner in burgundy nehru faux-military shit with a tight curly perm (and, erm, another girdle). Plus: the original series had those insane miniskirts, and alien chicks in lurex and body paint. And they had no budget for prosthetics, and so barely anyone had that goddamned forehead wrinkling so prevalent in all alien races from The Next Generation onward.
I will admit that this film looks icky, though. You can't recapture the magic of that dude in the giant lizard costume throwing polystyrene rocks about. Or Spock's kidnapped brain running the entire planet full of infantilised sexy ladeez. It's not going to happen.
Craig, you are a veritable font of wisdom today! I don't know whether I like 'From This Moment On' or 'Too Darn Hot' the best in
that film.
Ann Miller could only do one thing, but she was so brilliant at it. Luhrmann was probably wise not to do Chicago. I might have been even more annoyed with him...
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text:
Giuliani lends name to Marshals Museum fundraising
Artist's rendering of the proposed US Marshals museum to be built in Fort Smith.
Rudy Giuliani is helping out with fundraising efforts for the planned $50 million U.S. Marshals Museum in Fort Smith.The museum says the former New York mayor makes an appearance in a video that will be used to raise money for the new museum. Jim Dunn, the president and chief executive officer of the museum, says he's hopeful Giuliani will bring national attention to the project.Dunn says the former mayor understands the importance of the Marshals Service and the need to recognize the service's historic role.The Southwest Times Record reports (http://is.gd/sXIE0V ) that about $9 million has been raised locally for the museum and that organizers are now focusing on statewide and national fundraising efforts.
FORT SMITH, Ark. —
Rudy Giuliani is helping out with fundraising efforts for the planned $50 million U.S. Marshals Museum in Fort Smith.
The museum says the former New York mayor makes an appearance in a video that will be used to raise money for the new museum. Jim Dunn, the president and chief executive officer of the museum, says he's hopeful Giuliani will bring national attention to the project.
Dunn says the former mayor understands the importance of the Marshals Service and the need to recognize the service's historic role.
The Southwest Times Record reports (http://is.gd/sXIE0V ) that about $9 million has been raised locally for the museum and that organizers are now focusing on statewide and national fundraising efforts.
Marshals Museum receives state funds for project


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Cutting Edge: USP27X Deubiquitinates and Stabilizes the DNA Sensor cGAS to Regulate Cytosolic DNA–Mediated Signaling
Yunyun Guo, Fei Jiang, Lingli Kong, Bingqing Li, Yinlong Yang, Lei Zhang, Bingyu Liu, Yi Zheng and Chengjiang Gao
J Immunol October 15, 2019, 203 (8) 2049-2054; DOI: https://doi.org/10.4049/jimmunol.1900514
Yunyun Guo
*Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong 250012, People's Republic of China; and
Fei Jiang
Lingli Kong
Bingqing Li
†Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong First Medical Sciences, Jinan, Shandong 250062, People's Republic of China
ORCID record for Bingqing Li
Yinlong Yang
Bingyu Liu
ORCID record for Bingyu Liu
Chengjiang Gao
ORCID record for Chengjiang Gao
USP27X promotes deubiquitination and stabilization of cGAS.
USP27X deficiency impairs cGAS-mediated innate signaling.
USP27X positively regulates innate antiviral immunity to DNA viruses.
Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, catalyzes the formation of the second messenger 2′3′-cGAMP that binds to STING and triggers the type I IFN signaling. Activation of cGAS can be modulated by several protein posttranslational modifications, including ubiquitination. However, the cGAS activation regulated by protein deubiquitination remains poorly understood. In this study, we identified that deubiquitinase USP27X could interact with cGAS and cleave K48-linked polyubiquitination chains from cGAS, leading to cGAS stabilization. Consistently, knockout of Usp27x in mice macrophages resulted in an accelerated turnover of cGAS, decreased cGAMP production, phosphorylation of TBK1 and IRF3, and IFN-β production. Furthermore, Usp27x knockout mice macrophages showed impaired innate antiviral responses against HSV type 1 infection. Our data suggest that USP27X is a novel regulator of the cGAS–STING cytosolic DNA sensing pathway.
Activation of the innate immune system relies on several classes of germline-encoded pattern-recognition receptors, including TLRs, NOD-like receptors, retinoic acid–inducible gene I–like receptors (RLRs), and DNA sensors (1, 2). Cyclic GMP-AMP (cGAMP) synthase (cGAS), which belongs to the nucleotidyltransferase family, is one of the most important DNA sensors (3). Upon binding to DNA molecules, cGAS uses GTP and ATP to produce 2′3′-cGAMP, then cGAMP binds to the endoplasmic reticulum protein STING (also known as MITA, ERIS), leading to IRF3 activation and IFN-β production (4).
The cGAS–STING pathway is essential for the host to protect the host against a large variety of DNA-containing pathogens. However, aberrant activation of the cGAS pathway by self-DNA can also lead to autoimmune and inflammatory disease (5, 6). Thus, the cGAS pathway must be tightly regulated to prevent harmful activity arising from unrestrained signaling. Various posttranslational modifications modulate cGAS activity. The interaction between endoplasmic reticulum ubiquitin ligase RNF185 and cGAS specifically catalyzes the K27-linked polyubiquitination of cGAS, which promotes its enzymatic activity (7). TRIM56 induces the K335 monoubiquitination of cGAS, resulting in a marked increase of its dimerization, DNA-binding activity, and cGAMP production (8). TRIM38 catalyzes the sumoylation at K217 of cGAS in uninfected cells and during the early phase of viral infection, which prevented the polyubiquitination-dependent degradation of cGAS to facilitate an effective innate immune response to DNA viruses (9). Deubiquitination and ubiquitination are equally important in the normal functioning of organisms. Approximately 95 deubiquitinating enzymes (DUBs) are encoded in the human genome that falls into five families, but only 79 of them are predicted to be active deubiquitinases (10). In this regard, TRIM14 is found to recruit USP14 to cleave K48-linked ubiquitination of cGAS at K414 and mediate type I IFN signaling as well as antiviral immunity through the cross-talk with autophagy (11). However, it is not clear whether other DUBs can regulate cGAS deubiquitination directly and further participate in innate immunity. In this study, we demonstrated that USP27X directly interacts with cGAS and uses its enzymatic activity to cleave K48-linked polyubiquitin chains of cGAS, leading to the stabilization of cGAS protein. Importantly, we found that macrophages bearing the deletion of the Usp27x gene had less production of IFN-β and hence were more susceptible to HSV type 1 (HSV-1) infection. Thus, our findings demonstrate that USP27X contributes to innate immunity by directly regulating cGAS deubiquitination.
Reagents and Abs
cGAMP and polyinosinic:polycytidylic acid (poly[I:C]) were purchased from Invivogen. cGAMP and poly(I:C) were used at a final concentration of 50 and 10 μg/ml, respectively. HSV-60 is a 60-bp oligonucleotide containing viral DNA motifs derived from the HSV-1 genome. Rabbit anti–c-Myc Ab (A190-105A) was from Bethl Laboratories; rabbit anti-Flag Ab (PA1-984B) and rabbit anti-USP27X Ab (PA5-70389) were from Thermo Fisher Scientific; rabbit anti-hemagglutinin (HA) Ab was from Rockland; rabbit anti-cGAS Ab (D3080), mouse anti-Ub (P4D1), rabbit anti-P65 (D14E12), anti-pP65 (93H1), anti-IκB (44D4), anti-pIκB (14D4), anti-IKKβ (D30C6), anti-pIKKβ (C84E11), anti-IRF3 (D83B9), anti-pIRF3 (4D46), anti-TBK1 (3031S), and anti-pTBK1 (D52C2) were from Cell Signaling Technology; mouse anti-FLAG (M2) Abs were from Sigma-Aldrich; and HRP-conjugated goat anti-mouse or rabbit IgG Abs used for Western blotting were from Calbiochem.
Preparation of mouse peritoneal macrophages
Peritoneal macrophages were harvested and cultured as previously described (12).
Cells and viruses
HEK293T and RAW264.7 macrophages were obtained from the American Type Culture Collection. Sendai virus (SeV) was purchased from the China Center for Type Culture Collection (Wuhan University, China). Vesicular stomatitis virus (VSV) and HSV-1 were provided by H. Meng (Institute of Basic Medicine, Shandong Academy of Medical Sciences, China).
Generation of Usp27x-KO RAW264.7 macrophage through CRISPR-Cas9
To obtain the Usp27x-KO RAW264.7 cell lines, CRISPR-Cas9 genomic editing for gene deletion was used, as previously described (13). Guide RNA were designed and cloned into the vector lentiCRISPRv2. The guide RNA sequence used is as follows: Usp27x sg 5′-CACCGAATTAGTCCTCGTAAGCCGA-3′.
Plasmid constructs and small interfering RNA
The coding region of human USP27X and cGAS was amplified from human cDNA and subcloned into pCDNA3.1. The coding region of mouse Usp27x was amplified from mouse cDNA and subcloned into pLVX-IRES-Puro. HA-ubiquitin and other plasmids were described previously (12). The corresponding empty vectors were used as negative controls in all transfection experiments. The small interfering sequences against mice were as follows: Usp27x: 5′-GCGCTAGAGTCCTGCATA-3′, 5′-GCTCACTATGAAGAAGTTA-3′. Scramble small interfering RNA (siRNA) were used as a negative control in all RNA interference experiments.
The concentrations of IFN-β in culture supernatants were measured by ELISA kits (R&D Systems). The concentration of 2′-3′-cGAMP was measured by 2′-3′-cGAMP ELISA kit (Cayman Chemical).
Lentivirus preparation
Usp27x sequence was subcloned into pLVX-IRES-Puro vector, and the empty pLVX-IRES-Puro was used as a control. The lentivirus was produced by transient transfection of the pLVX-IRES-Puro-Usp27x construct or control vector into HEK293T cells using Lipofectamine 2000 (Thermo Fisher Scientific) with pLVX-IRES-Puro, pMD2.G, and psPAX2.
In vitro deubiquitination assay
Recombinant Myc-USP27X was expressed with a TNT Quick Coupled Transcription/Translation System (Promega), according to the instructions of the manufacturer. The in vitro deubiquitination assay was performed as previously described (14).
In vitro binding assay
Myc-USP27X and Flag-cGAS proteins were expressed with a TNT Quick Coupled Transcription/Translation System (Promega), according to the instructions of the manufacturer. Myc-USP27X and Flag-cGAS were mixed, followed by immunoprecipitation (IP) with Flag Abs and Western blotting with Myc Abs.
In vitro assay for cGAMP activity
The cGAMP activity assay was performed as described previously (15). RAW264.7 cells were transfected with HSV-60 for indicated time points and then homogenized by douncing in the hypotonic buffer. The homogenate was centrifuged at 100,000 rpm for 5 min. Then the supernatant was heated at 95°C for 5 min and centrifuged again at 12,000 rpm for 5 min to remove denatured proteins. The heat-resistant supernatant was incubated with 1 × 106 RAW264.7 cells in an 8-μl reaction containing 2 mM ATP, 1 U/μl benzonase, and 1.5 ng/μl perfringolysin O for 1.5 h at 30°C. Cells were lysed by adding 0.2% Nonidet P-40 and subjected to native gel electrophoresis. IRF3 dimerization was detected.
Plaque assays and detection of virus replication
The WT or Usp27x-KO RAW264.7 cells (2 × 106) were infected with VSV (multiplicity of infection [MOI] = 0.1) or HSV-1 (MOI = 10) for the indicated times. HSV and VSV plaque assay and replication were performed as described previously (12).
All data are presented as mean ± SD of one representative experiment. Statistical significance was determined with the one-way ANOVA, with a p value <0.05 considered statistically significant.
USP27X regulates cGAS deubiquitination
Previous studies have demonstrated that cGAS is modified by various types of ubiquitin chains, which is essential for antiviral immunity (7–9), whereas the cGAS deubiquitination is not well defined. To identify the DUBs that potentially regulate cGAS deubiquitination, we transfected DUB expression plasmids into HEK293T cells together with Flag-cGAS and HA-ubiquitin expression plasmids, then the ubiquitination of cGAS was analyzed through IP and Western blotting. We found that USP27X overexpression potentially attenuated cGAS ubiquitination(Supplemental Fig. 1).
To investigate whether attenuated cGAS ubiquitination depends on the enzymatic activity of USP27X, we transfected WT USP27X or its enzymatic activity mutant C87A into HEK293T cells together with Flag-tagged cGAS and HA-ubiquitin, and the cGAS ubiquitination was examined. The WT USP27X but not the mutant C87A led to a significant reduction of cGAS ubiquitination, indicating that attenuated cGAS ubiquitination requires USP27X enzymatic activity (Fig. 1A). We also performed an in vitro deubiquitination assay with recombinant USP27X protein. In this experiment, ubiquitinated cGAS was first immunoprecipitated from HEK293T cells transfected with Flag-cGAS and HA-ubiquitin plasmids, then recombinant USP27X was added in the in vitro deubiquitination assays. As shown in Fig. 1B, recombinant WT USP27X protein but not the mutant C87A protein was able to decrease cGAS ubiquitination. To exclude any artificial effect caused by overexpression and determine whether USP27X-mediated cGAS deubiquitination occurs in physiological conditions, we used CRISPR/Cas9 technology with a guide RNA specific to the mouse Usp27x gene to establish Usp27x-KO RAW264.7 macrophages and examined the endogenous cGAS ubiquitination. DNA sequencing and Western blot confirmed the success of Usp27x knockout in RAW264.7 macrophages (Supplemental Fig. 2A, 2B). The level of endogenous cGAS ubiquitination was obviously increased in Usp27x-KO RAW264.7 cells compared with that in WT cells upon IFN stimulatory DNA (ISD) stimulation (Fig. 1C). We also demonstrated that cGAS ubiquitination induced by HSV-1 infection was increased in Usp27x siRNA-transfected primary macrophages compared with that in control siRNA-transfected macrophages (Supplemental Fig. 1I). All together, these data suggest that USP27X regulates cGAS deubiquitination in a manner that is dependent on its DUB activity.
USP27X interacts with cGAS and regulates its deubiquitination. (A) Flag-cGAS and HA-ubiquitin (HA-Ub) were transfected into HEK293T cells together with USP27X or C87A, and cell lysates were subjected to IP with anti-Flag Ab, followed by Western blotting with HA Ab. (B) HEK293T cells were transiently transfected with Flag-cGAS and HA-Ub, then ubiquitinated cGAS was enriched with anti-Flag Ab. In vitro synthesized USP27X was incubated together with ubiquitinated cGAS in deubiquitylation assay buffer at 37°C for 1 h. The ubiquitination of cGAS was analyzed by Western blotting. (C) Usp27x knockout and counterpart macrophages were transfected with ISD and harvested at indicated times. The ubiquitinated cGAS was enriched with anti-cGAS Ab and detected with ubiquitin (Ub) Ab. (D) Co-IP was performed in lysates of HEK293T cells expressing Flag-cGAS and Myc-USP27X or C87A. (E) Flag-cGAS and Myc-USP27X were obtained by in vitro transcription and translation. Interaction between cGAS and Usp27x was assayed followed by IP with Flag Abs and Western blot with Myc Abs. (F) Co-IP was performed in lysates of peritoneal macrophages transfected with HSV-60 for indicated times. Similar results were obtained in three independent experiments.
USP27X interacts with cGAS
To further investigate how USP27X regulates cGAS deubiquitination, the interaction between these two proteins was measured. Co-IP with Flag Abs and Western blot with Myc Abs demonstrated that cGAS could interact with both USP27X WT and C87A in HEK293 cells (Fig. 1D). We also performed the in vitro binding assay with recombinant USP27X and cGAS proteins. Co-IP and Western blot demonstrated that USP27X associates with cGAS directly (Fig. 1E). Further, we showed that endogenous cGAS and USP27X could form a complex; notably, this interaction was enhanced upon HSV-60 transfection (Fig. 1F). USP14 has been demonstrated to regulate cGAS deubiquitination (11). However, USP14 and cGAS did not interact with each other directly; rather, USP14 was recruited to cGAS through TRIM14. We found USP14 could not decrease the cGAS ubiquitination in our screening experiments (Supplemental Fig. 1). This discrepancy may be caused by a lack of TRIM14 expression in HEK293T cells. Taken together, our data suggest that USP27X directly interacts with cGAS to regulate cGAS deubiquitination.
USP27X regulates cGAS stabilization
Protein ubiquitination can be divided into several forms according to the lysine residue used to form polyubiquitin chains, and different forms of ubiquitination have different functions (16, 17). To study the form of ubiquitin chains in cGAS that was cleaved by USP27X, we transfected Flag-cGAS and HA-ubiquitin or its lysine residue mutants with or without USP27X into HEK293T cells. As shown in Fig. 2A, overexpression of USP27X significantly decreased cGAS ubiquitination in WT and K48 ubiquitin transfected cells, indicating that USP27X mainly cleaved K48-linked polyubiquitin chain from cGAS. K48-linked ubiquitination usually leads to the degradation of target proteins through proteasome. Thus, we studied whether USP27X could inhibit cGAS protein degradation. Consistently, overexpression of WT USP27X in HEK293T cells increased Flag-cGAS protein level in a dose-dependent manner (Fig. 2B). In contrast, the cGAS protein level was not changed in C87A transfected cells (Fig. 2B). To further confirm USP27X regulates cGAS stability, we infected WT and Usp27x-KO RAW264.7 macrophages with HSV-1 and measured the cGAS protein expression. As shown in Fig. 2C, cGAS protein level was substantially decreased in Usp27x-KO macrophages compared with WT counterparts upon HSV-1 infection. Similarly, cGAS protein level was decreased in primary peritoneal macrophages transfected with Usp27x siRNA compared with those transfected with control siRNA (Fig. 2D). To directly confirm that USP27X regulates cGAS degradation, WT and Usp27x-KO RAW264.7 macrophages were first infected with HSV-1 for 4 h, then the protein synthesis inhibitor cycloheximide was used to treat the cells for different times. As shown in Fig. 2E, deficiency of Usp27x greatly accelerated the degradation of cGAS in RAW264.7 cells. Interestingly, we found that decreased cGAS protein levels in Usp27x-KO RAW264.7 cells could be partially restored by treatment of MG132 or chloroquine, indicating both proteasomal and autophagic degradation pathways are involved in USP27X-mediated regulation of cGAS protein (Fig. 2F). All together, these data demonstrated that USP27X interacts with cGAS to remove K48-linked ubiquitination and enhance cGAS stability.
USP27X regulates the stability of cGAS. (A) Flag-cGAS, HA-ubiquitin (HA-Ub), or its lysine residue mutants were transfected in HEK293T cells with or without Myc-USP27X. Co-IP assays were performed. (B) Flag-cGAS was transfected in HEK293T cells together with gradient amount of Myc-USP27X or C87A. cGAS protein level was detected by Western blot. (C) WT and Usp27x-KO RAW264.7 macrophages were infected with HSV-1 for the indicated times, then cGAS protein level was detected. (D) Primary peritoneal macrophages were transfected with Usp27x siRNA or scramble siRNA, infected with HSV-1 for the indicated times, and then cGAS protein level was detected by Western blot. (E) WT and Usp27x-KO RAW264.7 macrophages were infected with HSV-1 for 4 h, then treated with cycloheximide (100 μg/ml) for the indicated times. cGAS protein level was detected by Western blot. (F) WT and Usp27x-KO RAW264.7 cells were pretreated with MG132 or chloroquine (CQ) for 6 h, followed by HSV-1 stimulation for the indicated times. cGAS protein level was detected by Western blot. Quantification of cGAS protein levels relative to β-actin is shown in (B)–(F). Similar results were obtained in three independent experiments.
USP27X positively regulates intracellular DNA-induced innate signaling
Recognition of cytosolic DNA by cGAS led to the production of cGAMP, which binds to STING to promote the phosphorylation of TBK1 and IRF3, and then phosphorylated IRF3 dimerizes and translocates into the nucleus to induce type I IFN production (18–20). HSV-1 infection and ISD transfection could induce phosphorylation of IRF3 and TBK1 (Fig. 3A, Supplemental Fig. 2C). Phosphorylation of IRF3 and TBK1 induced by HSV-1 infection and ISD transfection was greatly decreased in Usp27x-KO RAW264.7 cells (Fig. 3A, Supplemental Fig. 2C). In contrast, cGAMP-induced phosphorylation of IRF3 and TBK1 was barely affected in Usp27x-KO RAW264.7 cells (Fig. 3A). Similarly, TBK1 and IRF3 phosphorylation was also decreased in primary peritoneal macrophages transfected with Usp27x siRNA compared with those transfected with control siRNA (Supplemental Fig. 3D). Interestingly, SeV- and poly(I:C)-induced phosphorylation of IRF3 and TBK1 were increased at late time points, indicating USP27X may negatively regulate RLR- and TLR3-mediated signaling (Supplemental Fig. 2D). HSV-1–induced phosphorylation of p65, IκB, and IKKβ was also decreased in Usp27x-KO RAW264.7 cells (Supplemental Fig. 2E). To directly confirm that Usp27x deficiency affects the phosphorylation of IRF3 and TBK1 on HSV-1 infection, we restored Usp27x expression in Usp27x-KO macrophage through transduction with Usp27x overexpression lentivirus. Overexpression of WT Usp27x, but not the enzymatic mutant C87A, rescued HSV-1–induced phosphorylation of IRF3 and TBK1 (Fig. 3B).
USP27X positively regulates intracellular DNA-induced innate signaling. (A) Western blot of phosphorylated (p) and total IRF3 and TBK1 in WT and Usp27x-KO RAW264.7 cells infected with HSV-1 (MOI = 10) or stimulated with cGAMP (50 μg/ml) for the indicated time points. (B) Western blot of phosphorylated (p) and total IRF3 and TBK1 in WT, Usp27x-KO, and Usp27x-KO RAW264.7 cells with overexpression of WT Usp27x or C87A mutant infected with HSV-1 (MOI = 10). (C) Native PAGE analysis of IRF3 dimerization in WT and Usp27x-KO RAW264.7 cells infected with HSV-1 (MOI = 10) or stimulated with cGAMP (50 μg/ml) for the indicated time points. (D) Quantitative PCR of Ifnb1 mRNA in WT and Usp27x-KO RAW264.7 cells infected with HSV-1 or stimulated with cGAMP for indicated time points. (E) ELISA for IFN-β production in culture supernatant from WT and Usp27x-KO RAW264.7 cells infected with HSV-1 or stimulated with cGAMP. (F) Quantitative PCR and ELISA analysis of Ifnb1 mRNA and IFN-β production in WT, Usp27x-KO, and Usp27x-KO RAW264.7 cells with overexpression of WT Usp27x or C87A mutant infected with HSV-1 (MOI = 10). Data are shown as mean ± SD of triplicates from one representative experiment in (D)–(F). Similar results were obtained in three independent experiments. **p < 0.01.
We further measured IRF3 dimerization on various stimulations. Consistent with IRF3 phosphorylation, IRF3 dimerization was also decreased in Usp27x-KO RAW264.7 cells transfected with HSV-1 or ISD compared with those in their control counterparts (Fig. 3C, Supplemental Fig. 2F). cGAMP-induced IRF3 dimerization was not changed between WT and Usp27x-KO macrophages (Fig. 3C).
To investigate whether Usp27x regulates IFN-β production, peritoneal macrophages were transfected with a scramble siRNA or Usp27x siRNA (Supplemental Fig. 3A). We found that knockdown of Usp27x expression greatly decreased Ifnb1 mRNA and IFN-β secretion in HSV-1–infected or ISD-transfected cells but not in cGAMP-stimulated cells (Supplemental Fig. 3B, 3C). Consistent with negative regulation of RLR- and TLR3-mediated signaling by USP27X, SeV- and poly(I:C)-induced expression of Ifnb1 mRNA was increased in Usp27x siRNA-transfected macrophages (Supplemental Fig. 3E). Knockout of Usp27x in RAW264.7 macrophages resulted in decreased expression of Ifnb1 mRNA expression on ISD transfection and HSV-1 infection. In contrast, cGAMP transfection-induced Ifnb1 mRNA expression was comparable in Usp27x-KO and WT cells (Fig. 3D, Supplemental Fig. 2G). SeV- and poly(I:C)-induced expression of Ifnb1 mRNA was increased (Supplemental Fig. 2G). We further found that secretion of IFN-β in response to HSV-1 infection, but not to cGAMP stimulation, was significantly impaired in Usp27x-KO RAW264.7 cells (Fig. 3E). Overexpression of WT Usp27x, but not the enzymatic mutant C87A in Usp27x-KO RAW264.7 cells, rescued HSV-1 infection-induced expression of Ifnb1 mRNA and IFN-β secretion (Fig. 3F). Collectively, these data indicated that USP27X is essential for the cytosolic DNA-induced innate signaling and IFN-β production.
USP27X regulates cGAMP production
cGAS is the enzyme responsible for the production of the second messenger cGAMP (3). To explore the function of USP27X-mediated deubiquitination and stability of cGAS, we measured cGAMP production in Usp27x-KO RAW264.7 cells after transfection with HSV-60. cGAMP levels in the stimulated cells were indirectly measured through IRF3 phosphorylation and dimerization. As expected, culture supernatant from WT macrophages stimulated with HSV-60 induced IRF3 phosphorylation and dimerization, whereas the culture supernatant from Usp27x-KO RAW264.7 induced less IRF3 phosphorylation and dimerization (Fig. 4A), indicating Usp27x-KO RAW264.7 cells produced less cGAMP on HSV-60 transfection compared with WT macrophages. We also measured the cGAMP production in Usp27x-KO cells after HSV-60 transfection using 2′3′-cGAMP ELISA Kit. Similar to the data of cGAMP-induced IRF3 activation, cGAMP production was decreased in Usp27x-KO cells compared with those in WT macrophages (Fig. 4B). Importantly, restoration of the WT Usp27x expression, but not the mutant C87A expression, in Usp27x-KO cells rescued HSV-60–induced cGAMP production. All together, these data suggested that USP27X regulates cGAMP production through deubiquitination of cGAS protein.
USP27X positively regulates cGAMP production and anti-DNA virus infection. (A) WT or Usp27x-KO RAW264.7 cells were stimulated with HSV-60 for indicated times, and extracts from these cells were used to prepare heat-resistant supernatants, which were delivered to permeabilized fresh RAW264.7 cells to stimulate IRF3 dimerization. (B) ELISA analysis of cGAMP production in WT, Usp27x-KO, and Usp27x-KO RAW264.7 cells with overexpression of WT Usp27x or C87A mutant stimulated with ISD transfection. (C and D) Plaque assay of HSV-1 titers and copy number of HSV-1 genomic DNA were measured in WT, Usp27x-KO, and Usp27x-KO RAW264.7 cells with overexpression of WT Usp27x or C87A mutant. (E and F) Plaque assay of HSV-1 titers and copy number of HSV-1 genomic DNA were measured in primary peritoneal macrophages transfected with Usp27x siRNA or control siRNA. Data are shown as mean ± SD of triplicates from one representative experiment in (C)–(F). Similar results were obtained in three independent experiments. **p < 0.01.
USP27X potentiates innate antiviral responses to DNA virus
Finally, we assessed if USP27X played a role in the regulation of DNA virus infection. WT and Usp27x-KO RAW264.7 cells were infected with HSV-1, and then the virus titer in the culture medium and genomic DNA copy of HSV-1 in the infected cells were measured by plaque assay and quantitative PCR, respectively. As a control, VSV was also used to infect the WT and Usp27x-KO cells. Plaque assay of RAW264.7 cells infected with HSV-1 showed that knockout of Usp27x greatly increased viral replication compared with that in WT infected cells (Fig. 4C). Consistently, the HSV-1 genomic DNA copy number was also significantly increased in the Usp27x-KO cells compared with WT cells (Fig. 4D). Importantly, restoration of WT Usp27x expression, but not the mutant C87A expression in Usp27x-KO cells, repressed HSV-1 replication (Fig. 4C, 4D). Knockdown of Usp27x expression in primary peritoneal macrophages through Usp27x siRNA also increased HSV-1 replication (Fig. 4E, 4F). In contrast, VSV replication was decreased in Usp27x-KO cells compared with that in WT cells (Supplemental Fig. 4A, 4B), indicating Usp27x positively regulates DNA virus infection but negatively regulates RNA virus infection.
Previous study reported that TRIM14 deficiency impairs type I IFN signaling by both HSV-1 and VSV infection via recruiting USP14 to deubiquitinate cGAS (11). In our study, we demonstrated that USP27X could directly form a complex with cGAS and cleave K48-linked ubiquitination from cGAS, leading to the stabilization of cGAS. Further, we deleted the Usp27x gene in RAW264.7 macrophages with CRISPR/Cas9 technology to assess the role of Usp27x in cytosolic DNA-mediated innate immunity. We found that Usp27x deficiency increased the K48-linked ubiquitination and turnover of cGAS and impaired DNA virus-induced cGAMP production, IRF3 phosphorylation, and IFN-β production.
We also found that USP27X plays different roles in the control of DNA virus and RNA virus infection. During HSV-1 infection, we found that USP27X targets cGAS to prevent its ubiquitination-dependent degradation; therefore, Usp27x-deficient RAW264.7 macrophages were more permissive to HSV-1 infection. During VSV infection, USP27X may target other signaling molecules to negatively regulate RNA virus infection. Thus, Usp27x deficiency in RAW264.7 macrophages repressed VSV replication. The specific mechanism for USP27X in the negative regulation of RLR signaling needs further investigation.
Overall, this study provides strong evidence that USP27X is responsible for the deubiquitination of cGAS and sheds light on the regulation of cGAS activation. Given the fact that cGAS–STING pathways play an important role in innate antiviral immunity and autoimmune diseases, USP27X may have therapeutic potential for the prevention and treatment of autoimmune diseases with aberrant DNA signaling.
The authors have no financial conflicts of interest.
This work was supported by grants from the National Natural Science Foundation of China (3173002 and 81525012 to C.G.).
The online version of this article contains supplemental material.
Abbreviations used in this article:
cGAMP
cyclic GMP-AMP
cGAS
cyclic GMP-AMP synthase
deubiquitinating enzyme
hemagglutinin
HSV-1
HSV type 1
IFN stimulatory DNA
multiplicity of infection
poly(I:C)
polyinosinic:polycytidylic acid
RLR
retinoic acid–inducible gene I–like receptor
Sendai virus
small interfering RNA
vesicular stomatitis virus.
Received May 9, 2019.
Accepted August 16, 2019.
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Diner, E. J.,
D. L. Burdette,
S. C. Wilson,
K. M. Monroe,
C. A. Kellenberger,
M. Hyodo,
Y. Hayakawa,
M. C. Hammond,
R. E. Vance
. 2013. The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Rep. 3: 1355–1361.
Ishikawa, H.,
G. N. Barber
. 2008. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. [Published erratum appears in 2008 Nature 456: 274.] Nature 455: 674–678.
You are going to email the following Cutting Edge: USP27X Deubiquitinates and Stabilizes the DNA Sensor cGAS to Regulate Cytosolic DNA–Mediated Signaling
Yunyun Guo, Fei Jiang, Lingli Kong, Bingqing Li, Yinlong Yang, Lei Zhang, Bingyu Liu, Yi Zheng, Chengjiang Gao
The Journal of Immunology October 15, 2019, 203 (8) 2049-2054; DOI: 10.4049/jimmunol.1900514
Cutting Edge: Subunit Booster Vaccination Confers Sterilizing Immunity against Liver-Stage Malaria in Mice Initially Primed with a Weight-Normalized Dose of Radiation-Attenuated Sporozoites
Cutting Edge: DOCK8 Regulates a Subset of Dendritic Cells That Is Critical for the Development of Experimental Autoimmune Encephalomyelitis
Cutting Edge: Lung-Resident T Cells Elicited by SARS-CoV-2 Do Not Mediate Protection against Secondary Infection
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It Works For Me. Wendy Clarke Shares Her Personal Writitng Rules.
This week I am delighted to welcome Wendy Clarke to talk about her writing and share the writing tips that have brought her such success in the short story world of women's magazines in recent years.
My stories are rarely fully formed when I start to write them. I generally have just the seed of an idea and occasionally the ending. I do not allow myself to overthink the story, but just start writing, and as I do, the story gradually unfurls like the petals of a flower.
It sounds obvious but it's surprising how many people will write something that they don't care about, just to fit in a particular market. If I don't like my own story, I can pretty much guarantee that nobody else will. If my story isn't something I'm proud of, I won't send it out - simple as that.
This can be taken in so many different ways: dialogue, adverbs, adjectives and descriptions in general. I love using description in my stories, but it has to be carefully done and mustn't distract from the all-important plot-line. I will dripfeed description into my stories a couple of sentences at a time. I want the reader to get the feel of the person/place I'm talking about, but not be swamped.
This is similar to the rule above, and is especially relevant to historical stories. Okay, so I've done my research and know everything there is to know about the Industrial Revolution or nursing in the 19th century. The magazine readers don't need to know, though... honestly they don't! I add any relevant information into my story sparingly, rather than give the reader a whole paragraph about the 1833 Factory Act or Louis Pasteur's germ theory.
Wendy Clarke is a full time writer of women's fiction. Since starting writing three years ago, she had sold over a hundred short stories and her work regularly appears in national women's magazines such as The People's Friend, Take a Break Fiction Feast and Woman's Weekly. She has also written serials and a number of non-fiction articles. Room in Your Heart and The Last Rose are Wendy's two collections of short stories. She has just finished her first novel.
Lovely to hear from you, Jen. I agree with you about the "less is more" and "don't info dump." As writers, we have to learn to trim things down. I'm glad you are enjoying this series.
I enjoy your short stories, Wendy, and thanks for sharing your writing tips with Susanna's readers. I chuckled when I read your advice about 'less is more' and 'don't info dump.' So true and those are areas of writing I've worked hard to address.
Another great blog in this series. Thank you both!
Thanks for your comments, Sue. I'm pleased you found Wendy's tips useful.
I'm glad you found it helpful, Sue. Thank you for commenting.
Thank you Wendy for sharing your writing rules with us. So interesting to read and extremely helpful.
Thank you for inviting me onto your blog to let your readers in on a few of my secrets, Susanna. I hope they are useful.
It was certainly a luxury to be able to use more description in my novel, Jan, but even then I had to be careful.
It's so tempting to put everything in isn't it, Frances. You spend such a lot of time doing the research that it seems a waste not to use it - still, there's always a next time.
Hi, Frances and Jan. Thank you both for your comments. Wendy's personal rules are ones that we all recognise and know the value of, I'm sure. The one about info dumping made me remember some books in which the authors had done precisely that - they were determined to share their knowledge, and it led to some clunky writing and unnatural dialogue.
It was interesting to read your tips, Wendy, and for me 'Less is more' is such a good piece of advice. Because I love words, it's too tempting to overdo the descriptions. Your point to drip feed and drop in carefully is something I need to follow. Thank you to you and Susanna.
Hi Wendy, I totally agree with all your writing tips, especially the one about knowing the time and place you're writing about, but not thrusting it down your readers' throats. It's so tempting to tell them interesting facts, isn't it?


Yuri Kostarev is the general manager of Ullman Sails Northwest Russia in St. Petersburg and Ullman Sails South Russia in Taganrog. With over 17 years of sailmaking experience, Yuri has been recognized as one of Russia's top sailmakers for over ten years. Yuri started his career building windsurfing sails and quickly expanded to all facets of sailing.
On the water, Yuri is a decorated sailor, winning the 2010 Micro class World Championships. He was involved with one of Russia's top Yngling teams from 2004-2008. In the loft, Yuri has designed and built sails for top one design and offshore competitors in classes from the Yngling to the Quarter Ton. The two sail lofts in St. Petersburg and Taganrog, plus a number of experienced dealers, all work with Yuri to deliver the best sails for their customer's sailing needs.


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Viewers Don't Trust TV Ads
A poll in the UK shows that less than 15% of TV viewers trust the messages given in TV ads.
A poll in the UK shows that less than 15% of TV viewers trust the messages given in TV ads, the Guardian reports:
Of 4,000 viewers questioned, around one in eight said they agreed with the statement "the commercials shown on ITV are truthful and accurate". Around half neither agreed nor disagreed, with one-third saying they disagreed.
MediaGuardian.co.uk | 'Trust me, I'm an advertiser'


Cashflow Problems? 5 Areas to Improve….
Cashflow – Most small business owners suffer from the same issues regarding this issue. If a business is to remain viable, it is imperative that the business generates positive cash flow consistently – year after year. When you have surplus cash you are better able to grow your business – and if you want to grow your business steadily – you will need to focus on profitability.
Non-payment or late-payment of supplier invoices.
If any (or all) of these signs appear familiar, then you need to take immediate Action to address them as your business, personal life, and health may also suffer from the stress they bring.
Weak Profit Margins – In many cases, this issue starts out small, we get it – you started your business, feel the need to compete on price so you discount or low-ball quotes just to win work. However, your supplier prices increase, and pretty soon you have a cash crunch.
Solution: Determine the total cost of delivering your products and services and compare these costs against actual revenues being generated. Do this for each product or service and modify (ie: increase the prices) or eliminate programs that don't perform.
High Overhead Costs – These are the costs associated with running your business such as rent, phone, etc. In some cases, under-performing revenues can be outweighed by these expenses, resulting in a cash-flow imbalance that can destroy your business.
Solution: Review overheads and eliminate expenses that are not absolutely necessary. For expenses that are required, then search for options that are less expensive.
Slow-Paying Clients – Clients that pay invoices slowly can be a massive drain on your cash flow. Allowing clients to pay on 30 – 60 day terms ties up cash in accounts receivable, so your business may well be profitable but cash poor.
Solution: Implement a collections system. Amend your terms to suit your business. Follow up with clients to make sure they pay on time. Consider offering an early payment incentive. Consider using a factoring service for slow-paying invoices, but only as a final option as you may incur a loss in the long run.
Bad Debt – This can happen when you extend credit to clients who then do not pay on-time or at all.
Excessive Inventory – Retail businesses can often have too much product on the shelf, and not moving out the door. This ties up your funds, potentially being a risk to the survival of the business.
Solution: Ideally, run on a lean-inventory strategy. Customers are conditioned to wait for products, so order goods once sales are confirmed. Operate a "just-in-time" delivery strategy that ensures that you do not carry inventory for very long.
Want more advice on your Cash Flow issues? Contact us now to arrange an obligation free meeting, and to claim your FREE hard copy of Instant Cashflow – the first ever best-selling book by Brad Sugars. Watch Brad's video review of the book here…..
When ActionCOACH North Brisbane started coaching way back in 1999, Business Coaching was fairly new and a lot of people hadn't heard about it. Then the word got out and now it is imperative for Business Owners to have a well-trained, highly-experienced "mentor" for their business. These days, more and more people are receiving the benefits from having a Business Coach – but there are still a lot of people who are still unsure as to why they should have a Business Coach…..What a Business Coach does….and how a Business Coach can help to grow their business.
These are all great questions…..


I'm on my fourth day of Perika 300mg x 3 daily. I feel like straight up poop. I am way more depressed than when I started taking this stuff. I am going to tough it out but this is sucky.
Day 5 - I dropped down to 2 a day and have noticed a drastic change. I did not think this would be necessary as I am a big boy..230 lbs.
I dont feel anchored down, depressed, with massive anxiety like yesterday. I actually am getting stuff done today and feel *kinda* good. Like its on its way or something.
I really hope this works.. I have been depressed for over 15 years. Hopeful at the moment.
I started May 15, 2018 so it has been 15 days for me at 600 mg a day (300 mg after breakfast and another 300 mg during late afternoon) and I haven't noticed an improvement in my mood. I've read that I should give it at least 6 weeks. I guess I'm impatient. I'm a slim guy, 137 # so I think I should stay at this dose instead of the recommended full dose of 900 mg a day. Can someone offer his or her thoughts?
Ramon what brand are you taking? If you are taking Perika I would suggest you try only 300mg at your weight since you are almost 100 lbs less than me. I usually require a higher dose than normal with other meds.
Ramon, you could also try to only take one tablet 300mg for one day only and then go back to two the following day and see how that helps. Since its basically a reverse of when you took that one extra and it started causing you problems. Your brain may be over-saturated with the drug and needs a little break. This is what happened to me for sure.
Hi Waggz, thanks so much for responding quickly. I feel desperate not getting any response when I need it most. I'm taking Perika standardized to 2% hyperforin. I just want to take it at the dose where I can get the maximum benefit without taking too much either. I'm concerned that if I only take 300 mg that it won't be effective. But I don't want to take 900 mg a day either since I think that would be too much for my body weight.
Just do this Ramon. Only take one today or tomorrow and see how you feel. Please do this and then let me know how you feel by midday tomorrow. If you feel worse then you can continue with two. I have a hunch that you will get this boost of energy and feel better if you only take one as did I. I still have not taken my second dose today and I feel great.
This test will be a confirmation to tell you if 600mg is indeed too much. If the test does not work you can always go back to taking two and then you should try upping the dose to 3 and test the same way.
I will try your suggestion about only taking one tablet (300mg) a day starting today. It's not that I was having any side effects from taking 2 tablets (600 mg) a day or feeling more depressed. I'm okay with it so far for the past 15 days. It's just that I have not yet felt a lift in my mood. Maybe it's too soon for me to expect any improvement at this time.
Ramon I know what you mean. We humans usually quantify more quantity with more better feeling.. but in this case it was less quantity that had the better feeling.
Lets keep our fingers crossed that you feel some changes by going down to one. If not then the next step is trying 3.
Thank you for taking time to respond and I appreciate all your input. I'm trying to stay hopeful.


Well it seems spring genuinely is here and it wasn't s false alarm. On Saturday evening I had couple of hours available in the evening so went to see if I could find the roe deer.
Upon arrival I was quickly deflated as the cows where still in the field the deer frequent meaning I was probably out of luck. However I have often seen them along the river so decided to try the tow path along the other side to see if that worked.
On the walk round I spotted this Small Tortoiseshell butterfly, a sign that spring really has sprung.
Slightly further round I heard a rustle and then noticed a deer was stuck between a laid hedge and the old fence. It soon jumped out and disappeared off into the woods. I don't know who was more startled me or the roe!
Once on the other side of the river my gamble soon paid off. I spotted a lone doe feeding in the long grass. She was aware of my presence, thanks to 1 badly placed step, but soon settled down back to feeding.
After a while she moved off into the woods. Further down I found 4 more deer, one was probably the doe from before but it was hard to tell. I tried to get a few images but the combination of distance and deer placement just meant nothing really worked out.
Deciding it wasn't working I left the deer in peace to feed and carried on down the path as I've only been down it once before and not this far. I found a SWT labelled gate and decided to follow it to see where it went. Turns out it comes out at one of the work areas for RHS Wisley Gardens, and also quite near my house.
This route lead me down a section of the River Wey I've not been down before. I've heard talk of kingfisher and this area looks promising with high mud banks and overhanging trees to fish from. Once the river calms down a touch and the water clears I'll be back to scout.
Nearly home there was one more surprise. In the final field I pass before coming back out into my road was a dog fox, just sat watching me.
After watching for a bit longer I saw a vixen in the long grass. She was spooked by me initially but soon relaxed again and headed off into the field to hunt.


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Calendar Leeds United
A man has been charged with assault on former Leeds manager Gary McAllister
Leeds United goalkeeper Kiko Casilla charged with racial abuse
Centenary celebrations for Leeds United
A 33 year old man has been charged with attacking former Leeds United manager & player Gary McAllister.
The Spaniard, 33, is alleged to have made discriminatory comments towards Jonathan Leko during a Championship match on September 28.
Celebrations include the unveiling of a blue plaque and a free party for fans in Leeds city centre
One of Leeds United's legends greatest goals immortalised in city mural
It has been created as part of the Mental Health charity Mind's Goals Get People Talking campaign, as part of World Mental Health Day.
Leeds United win FIFA Fair Play award
Marcelo Bielsa's men have been commended for their sportsmanship during the Best FIFA Football Awards in Milan
Barnsley and Leeds investigating crowd trouble at Oakwell
Leeds fans clashed with stewards in the away end and, in a separate incident, fighting also broke out in the east stand.
Documentary about Leeds United gets red-carpet premiere
A special premiere has been held for the first episode of a new documentary series, narrated by Russell Crowe, about his team Leeds United.
TRANSFER NEWS: Blades, Leeds, Wednesday and Hull are busy
Sheffield United made two late signings at the end of a busy transfer deadline day for all our clubs
Pontus Jansson leaves Leeds United
Swedish defender Pontus Jansson has left Leeds United to join fellow Sky Bet Championship side Brentford.
Leeds United sign Jack Harrison and Ben White
Leeds United have signed Manchester City winger Jack Harrison and Brighton defender Ben White on season-long loan deals.


President Nigeria Labour Congress, (NLC) Comrade Ayuba Wabba has called for an upward review of pension to help minimise economic hardship facing pensioners.
Wabba said this at the 16th edition of Pensioners Day Celebration in Abuja.
According to him, it is criminal that federal government pays N4000 as pension to some pension in this hard economy, if we want a better Nigerian than we must be willing to take care of our pensioners and workers.
" Our country is so blessed with various resources but it is a pity that we cannot account how it been spent.
" We got releases to pay six months out of 12 months been owed civil service pension out of the 36 month we have paid six month out of it.
" For police pension we paid them one year out of the 33 months and we just have a balance for 12 months for police pensions.
She said the essence of the verification was to make sure pensioners were fully capture so that there would not be need for them to come back again.


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Sheila Bonini
Senior Vice President, Private Sector Engagement
Sheila Bonini leads the private sector engagement team at WWF, overseeing a team of sustainability professionals supporting the organization's conservation mission. WWF works with more than 100 companies and that works spans from sustainability sourcing to awareness-raising, all with the goal of harnessing the power of the private sector as a force for conservation.
Sheila joined WWF from The Sustainability Consortium (TSC), a global organization focused on making consumer products more sustainable, where she served as Chief Executive Officer. In that capacity, she focused the organization on developing strategies and tools across the full product lifecycle that help to transform consumer goods supply chains. Prior to joining TSC, Sheila spent more than 15 years with the global consulting firm McKinsey & Company in the US, Europe and South America. Sheila served as senior expert consultant and co-leader of McKinsey's Sustainability Transformation Service, and her work focused on the link between social and environmental impact and financial value creation. Prior experience includes investment banking at Merrill Lynch and Goldman Sachs. Sheila received an AB degree in Applied Mathematics from Harvard University and an MBA from Stanford University Graduate School of Business.
Sheila is Participating in these Events
Leadership in Tracking Plastic Commitments and Translating them into Measurable Action - Keynote on Tuesday 19 November 2019 at 09:50:00


Car Auctions Yeovil | How To Find Government Car Auctions?
Car Auctions Yeovil. Related Posts. Government Car Auctions Bangalore. Police Car Auctions Wisconsin. Ex Government Cars Nz. Online Car Auctions Dallas Tx.
Yeovil Town Matchday Experience Survey.


Atria Windsor Woods is a warm independent and assisted living community that offers seniors all the comforts of home. Look forward to a fulfilling day with social opportunities, activities, educational programs and wellness events. Take a morning swim in our pool or enjoy a short walk outside; we offer countless opportunities to make the most of retirement living. We are located on 10 acres in Hudson, Florida, a suburb of Tampa, FL. Creating an environment of trust and companionship, Atria Windsor Woods provides the ultimate senior living experience, with delicious dining, dynamic calendars with more than 200 monthly events, and the freedom to choose which opportunities to explore next.
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The Carolina Way: Speech is Free (only for leftists)
Posted on August 30, 2013 by Brant Clifton
Fifty years ago, The University of North Carolina passed a Speaker Ban to clamp down on Marxist interlopers trying to poison the young skulls of mush matriculating in Chapel Hill. Of course, the lefties went nuts. Universities are about the sharing of ideas. Exposing people to all points of view, they said.
In 1968, the ban was overturned by the courts. The leftists rejoiced — hailing a new era of free speech and openness in the heart of Orange County.
Fast forward to the present day. In 2009, the university gained statewide and national publicity due to leftist fascists disrupting and shutting down on-campus speeches by conservatives Tom Tancredo and Virgil Goode. In 2013, student government at Carolina has cut the College Republicans' speakers budget by 75 percent. The Foundation for Individual Rights in Education is actively expressing concerns about the level of respect for The First Amendment at UNC-Chapel Hill. I guess those arguments from the 60s about hearing all kinds of points-of-view are no longer relevant.
I am an adjunct professor at two different college campuses here in North Carolina. I consider myself a libertarian-leaning conservative. But I do not attempt to brainwash students. I encourage debate. I expose my students to Ayn Rand, Peter Drucker and Milton Friedman. We discuss and debate the points in their works. I also offer in-depth explanations of the socialist and Marxist views on economics. I don't fail people for disagreeing with me.
One of my favorite professors during my undergrad years was a guy who admitted to the class he was a socialist. He and I had spirited debates about US foreign and domestic policies in class. He was respectful to me, and I was respectful to him. I think we both learned a lot by the end of the semester. (I got an 'A'.)
I try to live by some advice the late Tim Russert offered up about 20 years ago. I was working in DC, and was part of a small breakfast group that met monthly at The Jefferson Hotel. We regularly had media figures like Brit Hume, Sam Donaldson, George Will and Tim Russert join us for off-the-record discussions. Russert, then somewhat of a rookie with NBC news, was open about his Democrat background. But he told us something interesting about how he prepares for his on-air work. He talked about reading The Nation AND The National Review. He talked about reading The New York Times AND The Washington Times. Russert talked about how important it is to expose yourself to the work of folks you disagree with — as well as to the work of those you agree with. It makes you a much better-informed, more well-rounded person when you have a good understanding of the folks on the other side.
Mike Adams — the token conservative on the faculty at UNCW — recently made national news with an open letter he wrote to a liberal colleague who had slandered him for daring to express an opinion outside of the leftist orthodoxy. That lefty faculty member called Adams "the biggest embarassment to higher education in America." Adams responded by pointing out several wacky, bizarre events perpetrated by leftists on North Carolina campuses in recent years and asking which was more embarassing — Adams' comments or the antics of those leftists.
The media and the Democrats have lamented the rise of an alleged conservative revolution in North Carolina. Granted, the GOP has taken control of state government. But the left is firmly in control of higher education in North Carolina. We've got radical far-left misfits firmly ensconced in tenured roles — soaking up tax dollars to stoke white guilt, trash religion and bash capitalism. You have to look hard through the course catalogs to find courses that would be meaningful to young people setting out into the world with their diplomas seeking gainful employment.
The Republicans in Raleigh have a grand opportunity to reform The University of North Carolina system. I'm not suggesting turning the campuses into GOP training camps. How about actually pushing them into the position of (1) encouraging free thought and debate, and (2) providing more meaningful curriculum elements to aid students in the post-graduation world? A lot less African history, poverty studies, and feminist literature, and a whole lot more management, economics, marketing, entrepreneurship, American history and government. What kind of job can a load of feminist lit classes land you?
The Board of Governors and the various boards of trustees have a significant amount of influence in shaping the hiring and operational policies on campus. NCGA leaders could seek out people seriously committed to making fundamental lasting changes on the UNC campuses. But so far, we've seen an awful lot of rewarding of campaign contributors.
If you want a serious conservative revolution resulting in fundamental, long-lasting change — reforming UNC from the top down is a great place to focus your attention.
Education, Media, NC State Government, NCGOP, Politics
budget, College Republicans, North Carolina, speakers, UNC
Hagan to US House Speaker: Go, Johnny, Go !!!
Bob Pittenger needs a clue (and a primary)
2 thoughts on "The Carolina Way: Speech is Free (only for leftists)"
Outstanding post! This should be required reading for every legislator and member of the UNC Board of Governors and all the trustees of the various UNC institutions. The radical Democratic left has been brainwashing our college students for decades. Republicans are now in a position to address this issue; however, some Republicans seem clueless. Many Republican legislators now regret some of their choices for appointment to the Board of Governors.
Kirk D. Smith says:
Unfortunately, having worked among the progressives at a number of our institutions of higher indoctrination, it amazes me that they continue to raise the costs of higher education and there is no outcry from their leftist myrmidons! Where is the right portly Rev. Barber?
Our Army Reserve Officer Training Corps at the University of Rhode Island was able to secure from the Marxist led student union a paltry $2.95 for film to cover our trip to the Gettysburg National Battlefield back in 1996. The perversity crowd was allowed tens of thousands of dollars to host a annual four day Gay Fest!
These bloated institutions need to have their budgets seriously cut! Then we will hear the "wailing and gnashing of teeth!" It will be biblical!


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Washington Wizards sign Johnny O'Bryant
A source told ESPN that Johnny O'Bryant will sign a deal with the Washington Wizards.
O'Bryant was drafted by the Bucks with the number 36 overall pick in 2014 but has yet to make a serious impact in the NBA. He is a jump-shooting power forward that the Wizards could use to backup Markieff Morris and Andrew Nicholson if they were to rest. O'Bryant started 15 games as a rookie and played 66 total last year. He won't have any fantasy value.
Johnny O'Bryant will sign a deal with the Washington Wizards, source told ESPN.
— Jeff Goodman (@GoodmanESPN) September 10, 2016
Johnny O'BryantWashington Wizards
September 12, 2016, 12:14 pm


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College Basketball / UMBC
UMBC impresses in win over Vermont
by Tom Martin · February 21, 2019
Catonsville — Junior guard K.J. Jackson tallied 18 points on 7-13 from the field as he led his UMBC team to a 65-56 victory at home against the Vermont Catamounts (21-6, 11-2) Thursday evening.
Jackson was the catalyst the entire evening for the Retrievers offense, seemingly scoring at will when he drove into the paint. Even when he wasn't scoring, Jackson played tough defense, grabbing three defensive rebounds and accumulating two steals in 36 minutes of playing time.
Jackson's exploits, along with junior forward Arkel Lamar, who finished with 15 points, helped the Retrievers (18-10, 10-3) dominate the Catamounts in the paint, 40-24.
The Retrievers defense was extremely tough all evening. They held Vermont to just 17-47 from the field and 19 points under their season average.
The Catamounts could never seem to build momentum, partly because they committed 16 turnovers, several of which were unforced.
Vermont held the lead just once during the game when they inched ahead, 20-19, with 3:44 remaining in the first half. The next five points were then scored by UMBC junior guard Ricky Council II, and the Retrievers took a slim 26-25 lead into the locker room.
The game was still a one-point affair early in the second half, but the Retrievers would go on a 12-4 run over the next 5:37.
Vermont tried to get back in the game, cutting the lead to 44-38 with 11:32 left on the clock. However, UMBC answered with a 7-0 run over the next 3:01 to effectively putting the game on ice.
The Retrievers frustrated Vermont leading-scorer junior forward Anthony Lamb throughout the contest. Though Lamb did finish with 14 points, it was seven points under his average and he was only 5-14 from the field.
Perimeter defense was clearly a focus of head coach Ryan Odom, as his team held the Catamounts to 4-24 from three-point range, less than half their season average of 34%.
The Retrievers were clearly the tougher team. They made the Catamounts work hard for every opportunity, and forced the ball into the paint on offense on several occasions.
UMBC has now won nine of their last 10 games, and have jumped over Stony Brook to take sole possession on second place in the America East.
The win is also the third in a row for the Retrievers over the Catamounts. It's their first three-game win streak in the all-time series since the 2007-08 season. Vermont won all 23 contests between UMBC win streaks.
The Retrievers will now hit the road for two games in New York. Their first stop will be Saturday when they square off against UAlbany.
Tom Martin
Husband, father of three. Baltimore born and raised. UMBC '94. Follow me on Twitter -- @martymar1970
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