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"Carrie Fisher: Truthaholic"
What's not to love?
Carrie Fisher, addicted to brutal truth, delivered the fascinating details of her life with her classic self-effacing humor.
Well... 'Wishful Drinking' -- Ms. Fisher's memoir that also let's her fans know what her Wonder Bread years were like
Everyone has a 'readervoice' in their head that turns on when reading a book. You have your own style, and it works; besides, what else are you gonna do for a narrator?
When an author, who is also an actor, reads you their work, you know you're getting it exactly the way they wrote and meant it to be heard.
So you get the added novelty of filling in a sort of emotional gap between the author and audience.
You could... in my case we did listen to it from beginning to end while driving (skidding) through a torrential downpour while looking for an open restaurant on the backroads of Virginia one Sunday.
I loved it.
"Evidently Buddha is a Morning Person"
Not a bad book, just didn't like it as much as Merullo's the "Breakfast With Buddha."
Maybe it was the theme of death which set up the antagonism for the plot of the book. Maybe it was just me, having just finished "An Available Man" by Hilma Wollitzer, which also sponsored a newly minted widower. Maybe I was just tired of listening to a man lament the death of his wife, even if done in a decent, respectful way.
I do love the narrated voice of the Rinpoche as created by Sean Runnette. I love the personality Merullo paints for the Rinpoche.
Of course, at times, Merullo has the Rinpoche ask about an Americanism or slang or custom that you figure he must have already run into at least once in his sojourn in America, having interacted enough with the culture to marry an American and start a commune on its premises. These instances can seem like an obvious attempt at preaching to the choir in some aspects-- as can the somewhat contrived meetings with typical jerks who expose their prejudices too facilely and a trifle predictably and who just beg for an appropriate Buddhist dialogue which will set their errors aright.
I understand Merullo might want each Buddha book to stand alone and feels a new reader may need these set-ups, but reader of the Breakfast book might tire of the repetition.
In the long run, though, who am I to critique a book about a Buddhist monk? I can hear the Rinpoche laughing.
The sound of one hand not clapping.
"'An Available Man'... Starring: The Dialogue!"
Early in her book,Hilma Wolitzer presents her reader with the ultimate plot complication… a death. And from there, a tried and true plot line which is as old as cuneiform--how do the survivors cope afterwards. And, in some hands holding the quill, it can be a very tiresome and predictable contrivance.
However, she is a master at dialogue and therefore character development. I always feel that I'd read a 1,000 page novel about someone going to pick up bread at the grocery store if the author makes me care about the protagonist and their journey. Wolitzer definitely does that.
Also, Fred Sullivan is an excellent narrator.
You'll enjoy this book, I promise.
"The First Book I DID NOT Finish"
See the title.
The author might have more facility as a poet. The words are strung together beautifully. Unfortunately, the words don't develop characters that I actually care about.
I hated to do it but I gave up on it.
"Well… It's a Good, Not Great, Listen"
When I listened to the first hour or so of the book, I had really, really high hopes. Great descriptive writing and at first, really deep character development. Initially, I found that the primary characters had real foibles and color to their personality. Something to get your teeth into, as far as caring about their lives and relationships. But it seemed the author got tired of furthering that development and let them slip into less depth than the beginning promised. I can't go int the most disappointing aspects of the character plot lines without spoiling several critical plot junctures, so I won't. I'll just say, I didn't like the shallow twist(s) that occur several times with several characters.
I like science fiction type plots and this had promised to take its readers into a time-travel proposal without too much scientific glossing… just enough to suspend disbelief and to get the story moving. Unfortunately, as it moved along, it just felt like the book needed a little more guts to the temporal relationships.
The narrator is pretty good… although his cadence often remained static and could have used a little more interpretation of emotion at times.
Overall, a good listen but not one where you miss the characters at the end, as I was sure that I was going to at the beginning.
""What Alice Forgot" Is Not Forgettable, But…."
Liane Moriarty manages to take a tried and true soap operatic plot stand-by and make it interesting enough to keep a listener involved. Her characters are fun, intelligent and pretty well fleshed out. You feel you know them a few pages into the book and you do care what happens to them. Moriarty gets her readers invested in her characters, always the hallmark of an A+ author.
I enjoyed the book. You most likely will, also.
(FYI: The following is not really a spoiler since most of the synopses of the book explain the crux of the plot. But if you want an entirely fresh take, maybe you will want to skip my following insights, just in case I say something that takes too much from your own discoveries while listening. :)
So, as I was saying, BUT…..
If she had only pushed a little harder at the boundaries of what might possibly happen when someone becomes an amnesiac.
Moriarty early on conveys that the problem is more of a nuisance and strange interlude -- not one of a medical tragedy, so I guess I wanted more tangles and entertaining scenarios where Alice's memory loss gets her into a pickle. It just seems that the plot begged for some excruciatingly revealing but inadvertent situations that could put Alice in a situation that was comedic and still moved the plot along, too, based on her inability to recall most of her recent past.
There was a mix of the serious and the lighthearted, somewhat. But at times I couldn't tell if Moriarty wanted to get a little too dark, at the expense of the more lighthearted which was set at the beginning.
Anyway. There are well developed relationships and well written insights into the characters inner lives. There will be times that you want to yell at Alice, "Just ASK what happened!" But then, that is the point of the book and the involvement you have with it. And that makes it a pretty entertaining ride.
And one word about the narrator: Excellent.
"Murakami Takes a Literary Pilgrimage with His Readers"
I never quite knew where I stood with Haruki Murakami's hero, Tsukuru Tazaki. But that was not a bad thing.
I once read a novel by Joyce Carol Oates - I don't recall which one - but I remember thinking, as I dove deeper into it, that it was like climbing a brick wall with no end. I sort of felt this way while listening to Murakami's tale of the life of Tsukuru Tazaki. Was he a good man? Is he really a bad man? Where did my sympathies lie? Murakami gave me just enough information about his character to keep me involved in his life's journey while also feeling that I may not be getting the whole story on Tsukuru's flaws or better qualities. I will say it was quite the existential travel, like Sartre's "No Exit." Where was the moral compass I kept looking for from the narrator? But that structural vertigo did keep me interested in discovering the roots of Tsukuru's character.
Anyway. A good book keeps you thinking. Not only about the plot's twists and resolutions but also about the structure the author chooses to use. It seems to me, that this book could be used in Lit classes to excellent purpose.
Some reviews had mentioned they found the narrator's slight Japanese accent to be patronizing in some fashion. I didn't think of it that way. Since I was listening to a reading in English, of a Japanese novel, I felt it added color. (Ironically, given the book's title.) Like a person from Japan was telling me, in his second language, his story as we travelled on a long trip.
Also and lastly, I'll mention one of those weird synchronicity things that I often notice and think is kinda neat. Right after I finished the book I noticed Murakami had a short story The New Yorker. Also, I was in a bookstore not long after and saw another book by him on an endcap. Having never heard of Murakami until I found The Colorless Tsukuru Tazaki, I found it interesting. Of course, it probably just means Murakami is extra hot right now.
If you like a book written by a writer's writer, you'll find this book to your taste.
"King Earns a Crown With this One"
From the opening line to the last Stephen King brings his A-Game. You NEVER lose interest in this book. And it's a hefty tome.
I think just about everyone agrees that Stephen King's ability to breathe literary life into his characters is pretty much unchallenged in today's fiction field and he does a superb job of instilling pathos and humanity into all of his characters in this novel.
11/22/63 is part fantasy, much like all of King's work. But unlike a lot of his work (in which the fantastic lands in the horror genre,) this novel doesn't veer into the realm of the scary and undead. The main twist in this book includes a time flux in the plot's construction--which involves a lot of nostalgic play for anyone that was born in the fifties or sixties. Yet, the story is full of depth, which means anyone who loves an excellent character-based tale with nuanced intrigue will have no problem getting into this book.
And don't let the title cool your interest if you think the book heavily relies on a million facts about the assassination of JFK. It doesn't. That aspect creates a translucent "time period" backdrop for a really fine travel into one man's quest to create a different ending to many things.
This novel keeps you in that loop and waiting to discover if he succeeds.
"A Walk Through The High Weeds in Science"
I am not a physicist, biologist or nuclear scientist. But as a (somewhat) normal human with a (reasonable) amount of curiosity, I found this book engaging. I admit to not following every science based nuance and facet that the author presented in these 13 anomalies of the scientific world but I did feel that Michael Brooks had dumbed down the intricacies as much as was possible for the lay reader and still preserve the essential ingredients of the Things.
If you were drawn to the title, you will be drawn into the book's intriguing facts. The narration is superb and it's the type of book that can handle a second or third listen, just to nail down some of the fine points you may have missed during the first listen. If you've already read a few reviews & like what they say, you will find the unreasonable 13 Things excellent fodder for your gray matter to chew upon.
If you decide against listening to or reading 13 Things That Don't Make Sense, Mr. Brooks will have to edit the title to then read: 14 Things That Don't Make Sense.
"Tale of Old-New Orleans Well Paced"
First off, Doll-Baby is superbly narrated. January LaVoy masterfully adapts her reading to her characters' personalities and origins. This definitely gives the story depth and adds flesh to the bones of the individuals in the tale.
The story itself is good… it holds your interest, but Ms. McNeal often stunts her tale by a too simplistic sentence structure, which leaves the listener hoping for slightly more depth in the thought and personalities of her characters. Ms. LaVoy helps to add gradations of personal qualities which Ms. McNeal often neglects. Hence the three stars for the story itself and the five stars given the performance.
Some listeners may find the characters somewhat stereotyped. But in Ms. McNeal's defense, this seems to be a matter of the depths to which she wished to mine her players' inner life. Also, all of her characters are treated to the same level of development, which does give the story an even literary treatment. In other words, there isn't a lack of development in only some of the characters, there seems to be an overall reliance by Ms. McNeal to have the reader fill in the undefined gaps on all of her characters, while mainly giving a surface development to them all. That said, you do actually get enough grit in the story to get to know the players and to care what happens to them.
If you are interested in a (non-intellectually-taxing,) solid story of a young girl's coming-of-age in unexpected circumstances, you will enjoy Doll-Baby overall, at about that four-star level.
Just don't expect to discover the next Great American Novel.
"Black Diamonds: Pure Gold"
Well. If you love British History, especially the history which zeroes in on a particular family's life, then of course you will want to listen to "Black Diamonds."
This is a well researched and intriguing presentation of the history of the Fitzwilliam family and their relationship to the industry which supported them and the thousands of colliers who lived to mine their fortune of coal, or "black diamonds." That the mining of coal allowed a lopsided advantage of privileged wealth to the gentry while exacting a heavy toll (both physically and financially,) on the miners, is revealed in an interesting and engaging way by the author, Catherine Bailey.
By examining the rise and fall of the Fitzwillams, Ms. Bailey renders a good understanding of the economic relationship of English aristocracy and the people they employed while also fully coloring the manner in which industrial England transformed after the reformation of the ownership of the coal industry itself. Even with all the finely nuanced political and economic information which Ms. Bailey includes, it is never a dry read (or listen,) but a thoroughly gripping story of human trials, life and loves.
One last word. I need to throw some well-earned accolades toward the narrator, Gareth Armstrong. His performance, in which he easily switches from some very specific regional accents and back to his "neutral" narrative voice, is 100% on target. His abilities, (even when wrestling with the flattened vowels of an American voice,) are beyond expectation and render a full spectrum of character and depth to the book.
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trouble with my indoor tomato/jalapeno grow
I have recently built a hydro set-up and currently have 2 beter boy hybrid toms. and 2 early jalapenos. I am new to Hydro but have outdoor soil expeirience. Im having trouble with my leave tips hooking down and back. some of my tomato leaves are twisting as well. the first thing I notice was small irregulare light blotches on the bottom tomatoe leaves as well as a greyish patern on the same leave but on the jalapeno leaves. the roots are getting a brownish tint.
The system is a combo of an NFT with 1 sprayer and one fogger per plant spot. between each plant a fogger sprays as well. My pump was running at 8 times per day-every 3 hours. i run 400w MH with 5-5-5/gallon of flora series at 1.5 E.C. and P.H. set to 5.5-5.6 with each weekly change. it never drifts above 6.2-6.3. my E.C. stays pretty constant. Is that normal?
In order to combat the roots, i figured was watering too often, i reduced the time for the pump to run every 4 hours at 30min itervels. other than the leaves and roots, nothing else seems effected.
Could the leaf symptoms be caused by too much water? if anyone has came across similar symptoms could you please let me in on the good advice? it will be greatly appreciated. i would post a pic but i dont know how.
PH is fine. Keep temp below 65f.
This is what you need.
BROWN ROOTS-Do you use a "cleaner" what nutrients do you use? Get to your local hydro store and ask the person there about a "cleaner" and the generial hydroponic line. H202 can work good. empty your water then add new water. add H202 at the right ammount(you can find out online) let it run for 30 mins then add your nutes. Cleners kill off bad algae and other mold on the water. the blotchs on your leaves are most likely from your roots as most problems are. I see you use flora well go get flora shield!!!
So there you go. The answer to your problem is florashield.
I would want to see some pictures first. Brown roots aren't always a problem. Roots tend to discolor the older they get anyway, and the nutrients themselves can stain/tint the roots also. Nether is a problem, and natural. I'm more concerned with the statement:
"the first thing I notice was small irregulare light blotches on the bottom tomatoe leaves as well as a greyish patern on the same leave but on the jalapeno leaves."
That sounds like a mildew (fungus), like powdery mildew that starts as small dusty white or light gray spots, and grow together into a continues mat of fungus that resembles something like talcum powder on the plant. Mildew/fungus will also affect the overall health of the plant, and tomatoes are very susceptible to fungus problems. But again I would like to see some pictures before I assume there is a fungus problem. I would also like to know what the humidity level is/was. Powdery mildew thrives in dry climates, but needs damp spots, or areas of high humidity to germinate the spores first. Where Downy Mildew is probably more likely in wet climate, and/or high humidity situations, and look similar.
Like HH, I would like to see pics. Can you link them? Or just google how to post pics on here. I always have to do that as I forget every time.
I think we are missing info. What kind of water are you starting with? What nutes, exactly? What you are describing seems to me to be a lockout issue. The brown on the roots is often due to fall out of minerals. Maybe rusting iron? Ever seen all the rust on a bathroom wall of old homes where the iron in the mist collects on the wall? This is even worse in high pH water. Iron falls out faster and faster as you go above 7. The pH of your solution may be at 6, but that doesn't mean it's staying there when collected on the roots as the roots change the pH. As suggested, use a cleaner to remove the deposits.
Anyway, from the little info available, I'd hazard a guess at nute deficiency in the plant. Not necessarily in the solution. Often times, nute deficiency is a matter of uptake rather than content. So, don't go straight to adding nutes. The leaf curl can be a calcium deficiency or an over abundance of nitrogen or even both. Calcium helps make the cells strong. Nitrogen increases growth speed. Sometimes it happens faster than all the cells can handle and you get distortion in the leaves. Very common in peppers as people tend to over fertilize them. Especially if they put them in the same system as tomatoes. They have very different needs. Hard to say if this is happening without seeing the plants in a good, true color pic (no adjustments due to flash or backlight compensation). The spots can be a magnesium or calcium deficiency. Others, too, but these are common ones. Again, need to see the plants.
Again without seeing any pictures, it's really hard to come to any conclusions. But here a few links with symptoms and pictures of powdery, and downy mildew. The symptoms sound more similar to the downy mildew to me, with both the curling leaves, and spots on the leaves. But powdery mildew also causes pour plant health as well.
Downy Mildew
Quote taken from the above link:
Symptoms can be confused with other plant problems. Leaves may become mottled and yellowed, resembling nutritional deficiencies. On some plants, downy mildew infection may look similar to injury from foliar nematodes. In both cases, angular lesions are bounded by leaf veins. However, downy mildew infection results in a soft, fluffy gray, brown or purple fungal sporulation developing on the underside of leaves. On coreopsis, the fungal sporulation is white.
Symptoms can also vary depending upon the host plant. On snapdragons, infected plants are yellow and stunted. You may see downward leaf curling on the young seedlings. On salvia, angular yellow blotches can be seen between the leaf veins. On pansy, leaves turn mottled and off-color with purple blotches. Pale green or yellow patches develop on geum. Purplish patches occur on lamium and veronica. On roses, leaves develop angular dark purple to black areas and may turn yellow and drop."
Some more links with symptoms and pictures
Downy mildew on grapevines
Powdery mildew
Powdery Mildew Quick Facts
Easy to tell if it's either of the mildews: Are the spots fuzzy or look like they have powder sugar on them? They will if it's either of those. I doubt it's the problem, though.
First, the original post doesn't mention fuzz/powder and I have a feeling it would have. Of course, it could have been an oversight.
Second, neither of these are particularly known for tomato and peppers indoors. Sometimes in a greenhouse, but that's due to the spores being carried in on the wind and through the vent system and the humidity in a greenhouse make ideal conditions for spore adherence. Plus, it's really too early for mildew spores in KS. There hasn't been enough outside foliage to propagate them, which means they also aren't likely to have been carried in from outside. Give it another couple weeks, though.
Third, neither cause brown roots, but some things that cause brown roots do cause the symptoms described. So, if it's either of the mildews mentioned, that's independent of the brown roots. The brown roots could (though not necessarily) be an indicator of a nute issue whether you have the mildew problem or not.
Ya, I agree. That's why I would have liked to see some pictures. But in case the original poster couldn't post them, I wanted to post some links to descriptions and pics so they could see if that seems like what they are experiencing. Also as you mentioned regardless, that doesn't mean there is only one issue they are dealing with or not. But I'm guessing that at the time of the original post when noticing the irregular light blotches, as well as the grayish spots, simply noticing if they were a fuzzy or dusty substance was as you mentioned, just an oversight or missing information. And the light blotches wouldn't necessarily need to be fuzzy or dusty for the downy mildew on the tops of the leaves (where I think they were noticed), so assuming they are on the tops of the leaves, and the fungus is on the bottom of the leaves, it sure seems to fit the situation.
Even though the fungus needs to be growing to propagate the spores, the spores will only need air current to travel, and the spores are seeds that will survive winters. Once they make it into a greenhouse, it's not winter for the spores anymore, and will germinate anytime conditions are favorable. The downy mildew even prefers "cool" moist conditions, and can also cause the leaf curl (that's being experienced).
But the reason that I don't really focus on the statement about the brown roots is mainly because there are brown roots, and then there are brown roots. Everyone's idea of what's brown is, is different. Basically there are many shades of brown, and the original posters statement was "the roots are getting a brownish tint." To me that suggests that they seem to be going form a solid and/or bright white that they are used to seeing, to a slight off-color (brownish).
And as I mentioned, older roots tend get a brown tint anyway. The poster never said how old the plants were that I remember, and I assume they are not exactly young plants. Also some nutrients will naturally give the roots a brownish tint as well, even if so. So without any more information or pictures to go on, I simply don't see the statement of the roots getting a brownish tint as a problem or issue at this point. But that's not to say it isn't the first visible sign of a problem, or even to say that there isn't another issue going on as well.
oops. sorry guys for the delay on the post. I have been searching my ass off! I figured out the prob. I belive it is a combonation of powdery mildew as well as a root rot problem. But i dont think the roots are too awful bad. I went back to the hydro store and picked up some hydrozome. I have been emptying my res and scrubbing with alcohol(Ive been told H202 kills ALL bacteria. she said you need some GOOD bacteria for the plant to do good). After that i run flora kleen through for a few hours. when i topped back up I put low lewel amounts of Hydrozome as well as- belive it or not! Superthrive-I figured it could help with stress. just 1 drop a gallon! After trimming the worst roots I hit the leaves with sulfer for the Mildew and, voila!!! It seems to be dooing great. it is back to rapid growth already. 2 weeks of that is all it took. The roots that looked best are growing feeder hairs like crazy! I plan on continueing this regimine for a while to make sure no rot is continuing. Oh yeah, I also increased the slope of my trough as well as added extra air stones.
Thanks for the help!!!

subset: commoncrawl


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Today on Current State: Lansing city budget; Red Cedar now open for fishing ; Wharton Center reveals new season; and a Public Poetry Announcement with Carl Phillips.
Yesterday the Lansing City Council continued discussions about one of the most challenging parts of next fiscal year's budget--spending for city police services. Mayor Virg Bernero's proposed spending plan for the 2014 fiscal year includes a $700,000 cut to the police budget.
The Wharton Center for Performing Arts announced its 2013-14 season Monday evening. Peter Whorf spoke with Wharton Executive Director Mike Brand about some of the highlights, including The Book of Mormon and the St. Petersburg Philharmonic Orchestra.
Carl Phillips went from a high school Latin teacher to one of the most prestigious positions in American letters, a chancellor of the Academy of American Poets. The world-renown poet and professor at Washington University-St. Louis discusses his career and reads one of his poems ahead of his visit to Michigan State University on Wednesday.


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£680,000 Under Offer 4 Bedrooms Heightington, Bewdley, Worcestershire, DY12
A Superb Barn Conversion Consisting of Three Wings Around a Central Courtyard, Offering Extremely Versatile Accommodation Of Around 3162.5 Sq. Ft. Set Within Over 2 Acres.
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Worcester 20 miles Birmingham 26 miles M5 (J5) & (J3) 20 miles Bewdley 5 miles Kidderminster 8 miles (Distances approximate) A stunning, modern property situated on the edge of the Wyre Forest.
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The athletic department from Doctors Hospital held an Athletic Training Clinic at Grovetown High School, Saturday.
Greenbrier holds an undefeated record against all other county teams this season and a No. 1 state ranking in AAAA baseball.
Third Grade A...
While golf dominates Masters Week, there are several Spring Break camps for children.
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Patient OPTION Act would repeal Obamacare, allowing citizens to deduct healthcare expenses from their taxes.
Rather than continue to ride the state's prekindergarten roller-coaster, Columbia County should just step away.
You're supposed to pay sales taxes on Internet purchases, but most people don't because they aren't forced to do so.
Lawmakers and lobbyists alike had little time to study the tax reform bill rushed through the Georgia Legislature.
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- Is the oil industry subsidized much more than the electrified vehicle industry?
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- Leaf number 75,000 sold in the US -Is Volt du…Posted 6 days ago
Anyone who reads this site regularly knew this was coming ...
Does it matter? Will we see a turnabout?
Since the Volt and Leaf were launched the very same month in December…
Car is 8 months old and I'm buying a tire
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Posted on 28 March 2015 by electricAnt
5 replies | 176 views
Anyone know why the EVSE clicks at all when plugged in to the car but the car is not charging up due to delayed charge mode? I figure if fans are...
Finally (!) some advertising: 'Tomorrowland' movie will advertise Chevy Volt, E-NVs
Posted on 28 March 2015 by Bammerman
3 replies | 360 views
Seen this morning:
Autoline gen 2 Volt interview
Posted on 28 March 2015 by Scupper
5 replies | 549 views
For those that haven't seen it yet...
Thank You Volt Advisor!
Posted on 28 March 2015 by sectime
5 replies | 507 views
About a month ago my Volt, while driving, would emit a loud pop in the right rear C pillar area. I'm talking like a baseball or rock hit very loud....
Who covers towing for roadside assistance?
Posted on 29 March 2015 by llninja
3 replies | 172 views
In a different thread, my son hit a deer with my volt, punctured the radiator, and he hit the Onstar button to get it flat bedded to the dealership....
AGM Battery Replacement thoughts
Posted on 29 March 2015 by Miredian
5 replies | 231 views
My '13 Volt is about to turn three as it was assembled in early '12 I'm thinking I'd like to replace the 12v battery on my own. Anyone done this?...
How is Volt in deeper snow?
Posted on 28 March 2015 by caryrae73
9 replies | 274 views
Thinking about a Volt as my next car when the time comes. It looks like the volts front end is pretty low to the ground so for anyone who knows how...
Extremely Bad Experience with OnStar
Posted on 28 March 2015 by edwardang
3 replies | 277 views
Last night, 51 miles into my 220-mile trip, I got a flat tire on the freeway. I was able to exit the freeway and pull over safely onto a parking...
Looking for help to diagnose possible noises under the car when going over bumps
Posted on 28 March 2015 by Prohidium
7 replies | 369 views
In the colder weather, my 2013 volt will have a "knocking sound" under the body of the car when going over bumps. The knocking sound appears to be in...
'16 Volt to appear in a Disney's Tomorrowland
Posted on 28 March 2015 by bro1999
2 replies | 311 views
Along with the EN-V concept. It seems there will be advertising for the Volt linked to the movie as well. Tomorrow comes out May 22nd....my bet is...
CA Volt visiting BC
Posted on 28 March 2015 by Rampage_Rick
0 replies | 238 views
Spotted another Volt in town today, first time I've seen another Topaz Blue in the wild, definitely the first out-of-province sighting. Must have...
Torklift EcoHitch Stealth Install
Posted on 28 March 2015 by omaharacer
2 replies | 318 views
I just finished installing my Torklift Ecohitch "Stealth" on my 2015 Volt. I'm sure this has been posted a few times already, however I couldn't find...


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Publications (24)284.73 Total impact
Article: Monoacylglycerol Lipase Inhibitor JZL184 Improves Behavior and Neural Properties in Ts65Dn Mice, a Model of Down Syndrome.[Show abstract] [Hide abstract]
ABSTRACT: Genetic alterations or pharmacological treatments affecting endocannabinoid signaling have profound effects on synaptic and neuronal properties and, under certain conditions, may improve higher brain functions. Down syndrome (DS), a developmental disorder caused by triplication of chromosome 21, is characterized by deficient cognition and inevitable development of the Alzheimer disease (AD) type pathology during aging. Here we used JZL184, a selective inhibitor of monoacylglycerol lipase (MAGL), to examine the effects of chronic MAGL inhibition on the behavioral, biochemical, and synaptic properties of aged Ts65Dn mice, a genetic model of DS. In both Ts65Dn mice and their normosomic (2N) controls, JZL184-treatment increased brain levels of 2-arachidonoylglycerol (2-AG) and decreased levels of its metabolites such as arachidonic acid, prostaglandins PGD2, PGE2, PGFα, and PGJ2. Enhanced spontaneous locomotor activity of Ts65Dn mice was reduced by the JZL184-treatement to the levels observed in 2N animals. Deficient long-term memory was also improved, while short-term and working types of memory were unaffected. Furthermore, reduced hippocampal long-term potentiation (LTP) was increased in the JZL184-treated Ts65Dn mice to the levels observed in 2N mice. Interestingly, changes in synaptic plasticity and behavior were not observed in the JZL184-treated 2N mice suggesting that the treatment specifically attenuated the defects in the trisomic animals. The JZL184-treatment also reduced the levels of Aβ40 and Aβ42, but had no effect on the levels of full length APP and BACE1 in both Ts65Dn and 2N mice. These data show that chronic MAGL inhibition improves the behavior and brain functions in a DS model suggesting that pharmacological targeting of MAGL may be considered as a perspective new approach for improving cognition in DS.PLoS ONE 12/2014; 9(12):e114521. DOI:10.1371/journal.pone.0114521 · 3.53 Impact Factor
Article: Global Identification of Caspase Substrates Using PROTOMAP (Protein Topography and Migration Analysis Platform).[Show abstract] [Hide abstract]
ABSTRACT: Delineation of the natural substrate scope of proteases is important for understanding the functions of proteolytic pathways in physiology and disease. Herein we describe the protocol for PROTOMAP, a technique that combines SDS-PAGE with tandem mass spectrometry to globally identify shifts in protein migration indicative of proteolytic processing. When applied to cells undergoing apoptosis, this unbiased global method provides a snapshot of the topography and magnitude of proteolytic events associated with programmed cell death.Methods in molecular biology (Clifton, N.J.) 01/2014; 1133:61-70. DOI:10.1007/978-1-4939-0357-3_3 · 1.29 Impact Factor
Nature Chemical Biology 03/2013; 9(4):200-205. DOI:10.1038/nchembio.1211 · 12.95 Impact Factor
Article: Functional interplay between caspase cleavage and phosphorylation sculpts the apoptotic proteome.[Show abstract] [Hide abstract]
ABSTRACT: Caspase proteases are principal mediators of apoptosis, where they cleave hundreds of proteins. Phosphorylation also plays an important role in apoptosis, although the extent to which proteolytic and phosphorylation pathways crosstalk during programmed cell death remains poorly understood. Using a quantitative proteomic platform that integrates phosphorylation sites into the topographical maps of proteins, we identify a cohort of over 500 apoptosis-specific phosphorylation events and show that they are enriched on cleaved proteins and clustered around sites of caspase proteolysis. We find that caspase cleavage can expose new sites for phosphorylation, and, conversely, that phosphorylation at the +3 position of cleavage sites can directly promote substrate proteolysis by caspase-8. This study provides a global portrait of the apoptotic phosphoproteome, revealing heretofore unrecognized forms of functional crosstalk between phosphorylation and caspase proteolytic pathways that lead to enhanced rates of protein cleavage and the unveiling of new sites for phosphorylation.Cell 07/2012; 150(2):426-40. DOI:10.1016/j.cell.2012.05.040 · 31.96 Impact Factor
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ABSTRACT: Cysteine is the most intrinsically nucleophilic amino acid in proteins, where its reactivity is tuned to perform diverse biochemical functions. The absence of a consensus sequence that defines functional cysteines in proteins has hindered their discovery and characterization. Here we describe a proteomics method to profile quantitatively the intrinsic reactivity of cysteine residues en masse directly in native biological systems. Hyper-reactivity was a rare feature among cysteines and it was found to specify a wide range of activities, including nucleophilic and reductive catalysis and sites of oxidative modification. Hyper-reactive cysteines were identified in several proteins of uncharacterized function, including a residue conserved across eukaryotic phylogeny that we show is required for yeast viability and is involved in iron-sulphur protein biogenesis. We also demonstrate that quantitative reactivity profiling can form the basis for screening and functional assignment of cysteines in computationally designed proteins, where it discriminated catalytically active from inactive cysteine hydrolase designs.Nature 11/2010; 468(7325):790-5. DOI:10.1038/nature09472 · 42.35 Impact Factor
Article: Superfamily-wide portrait of serine hydrolase inhibition achieved by library-versus-library screening.[Show abstract] [Hide abstract]
ABSTRACT: Serine hydrolases (SHs) are one of the largest and most diverse enzyme classes in mammals. They play fundamental roles in virtually all physiological processes and are targeted by drugs to treat diseases such as diabetes, obesity, and neurodegenerative disorders. Despite this, we lack biological understanding for most of the 110+ predicted mammalian metabolic SHs, in large part because of a dearth of assays to assess their biochemical activities and a lack of selective inhibitors to probe their function in living systems. We show here that the vast majority (> 80%) of mammalian metabolic SHs can be labeled in proteomes by a single, active site-directed fluorophosphonate probe. We exploit this universal activity-based assay in a library-versus-library format to screen 70+ SHs against 140+ structurally diverse carbamates. Lead inhibitors were discovered for ∼40% of the screened enzymes, including many poorly characterized SHs. Global profiles identified carbamate inhibitors that discriminate among highly sequence-related SHs and, conversely, enzymes that share inhibitor sensitivity profiles despite lacking sequence homology. These findings indicate that sequence relatedness is not a strong predictor of shared pharmacology within the SH superfamily. Finally, we show that lead carbamate inhibitors can be optimized into pharmacological probes that inactivate individual SHs with high specificity in vivo.Proceedings of the National Academy of Sciences 11/2010; 107(49):20941-6. DOI:10.1073/pnas.1011663107 · 9.81 Impact Factor
Article: LDL Receptor-Related Protein 1 Regulates the Abundance of Diverse Cell-Signaling Proteins in the Plasma Membrane Proteome[Show abstract] [Hide abstract]
ABSTRACT: LDL receptor-related protein 1 (LRP1) is an endocytic receptor, reported to regulate the abundance of other receptors in the plasma membrane, including uPAR and tissue factor. The goal of this study was to identify novel plasma membrane proteins, involved in cell-signaling, that are regulated by LRP1. Membrane protein ectodomains were prepared from RAW 264.7 cells in which LRP1 was silenced and control cells using protease K. Peptides were identified by LC-MS/MS. By analysis of spectral counts, 31 transmembrane and secreted proteins were regulated in abundance at least 2-fold when LRP1 was silenced. Validation studies confirmed that semaphorin4D (Sema4D), plexin domain-containing protein-1 (Plxdc1), and neuropilin-1 were more abundant in the membranes of LRP1 gene-silenced cells. Regulation of Plxdc1 by LRP1 was confirmed in CHO cells, as a second model system. Plxdc1 coimmunoprecipitated with LRP1 from extracts of RAW 264.7 cells and mouse liver. Although Sema4D did not coimmunoprecipitate with LRP1, the cell-surface level of Sema4D was increased by RAP, which binds to LRP1 and inhibits binding of other ligands. These studies identify Plxdc1, Sema4D, and neuropilin-1 as novel LRP1-regulated cell-signaling proteins. Overall, LRP1 emerges as a generalized regulator of the plasma membrane proteome.Journal of Proteome Research 10/2010; 9(12):6689-95. DOI:10.1021/pr1008288 · 5.06 Impact Factor
Article: Global profiling of proteolysis during rupture of Plasmodium falciparum from the host erythrocyte.[Show abstract] [Hide abstract]
ABSTRACT: The obligate intracellular parasite pathogen Plasmodium falciparum is the causative agent of malaria, a disease that results in nearly one million deaths per year. A key step in disease pathology in the human host is the parasite-mediated rupture of red blood cells, a process that requires extensive proteolysis of a number of host and parasite proteins. However, only a relatively small number of specific proteolytic processing events have been characterized. Here we describe the application of the Protein Topography and Migration Analysis Platform (PROTOMAP) (Dix, M. M., Simon, G. M., and Cravatt, B. F. (2008) Global mapping of the topography and magnitude of proteolytic events in apoptosis. Cell 134, 679-691; Simon, G. M., Dix, M. M., and Cravatt, B. F. (2009) Comparative assessment of large-scale proteomic studies of apoptotic proteolysis. ACS Chem. Biol. 4, 401-408) technology to globally profile proteolytic events occurring over the last 6-8 h of the intraerythrocytic cycle of P. falciparum. Using this method, we were able to generate peptographs for a large number of proteins at 6 h prior to rupture as well as at the point of rupture and in purified merozoites after exit from the host cell. These peptographs allowed assessment of proteolytic processing as well as changes in both protein localization and overall stage-specific expression of a large number of parasite proteins. Furthermore, by using a highly selective inhibitor of the cysteine protease dipeptidyl aminopeptidase 3 (DPAP3) that has been shown to be a key regulator of host cell rupture, we were able to identify specific substrates whose processing may be of particular importance to the process of host cell rupture. These results provide the first global map of the proteolytic processing events that take place as the human malarial parasite extracts itself from the host red blood cell. These data also provide insight into the biochemical events that take place during host cell rupture and are likely to be valuable for the study of proteases that could potentially be targeted for therapeutic gain.Molecular & Cellular Proteomics 10/2010; 10(5):M110.001636. DOI:10.1074/mcp.M110.001636 · 7.25 Impact Factor
Article: The glycerophospho metabolome and its influence on amino acid homeostasis revealed by brain metabolomics of GDE1(-/-) mice.[Show abstract] [Hide abstract]
ABSTRACT: GDE1 is a mammalian glycerophosphodiesterase (GDE) implicated by in vitro studies in the regulation of glycerophophoinositol (GroPIns) and possibly other glycerophospho (GroP) metabolites. Here, we show using untargeted metabolomics that GroPIns is profoundly (>20-fold) elevated in brain tissue from GDE1(-/-) mice. Furthermore, two additional GroP metabolites not previously identified in eukaryotic cells, glycerophosphoserine (GroPSer) and glycerophosphoglycerate (GroPGate), were also highly elevated in GDE1(-/-) brains. Enzyme assays with synthetic GroP metabolites confirmed that GroPSer and GroPGate are direct substrates of GDE1. Interestingly, our metabolomic profiles also revealed that serine (both L-and D-) levels were significantly reduced in brains of GDE1(-/-) mice. These findings designate GroPSer as a previously unappreciated reservoir for free serine in the nervous system and suggest that GDE1, through recycling serine from GroPSer, may impact D-serine-dependent neural signaling processes in vivo.Chemistry & biology 08/2010; 17(8):831-40. DOI:10.1016/j.chembiol.2010.06.009 · 6.52 Impact Factor
Article: Characterization of mice lacking candidate N-acyl ethanolamine biosynthetic enzymes provides evidence for multiple pathways that contribute to endocannabinoid production in vivo.[Show abstract] [Hide abstract]
ABSTRACT: The biosynthesis of the endocannabinoid anandamide (AEA) and related N-acyl ethanolamine (NAE) lipids is complex and appears to involve multiple pathways, including: (1) direct release of NAEs from N-acyl phosphatidyl ethanolamine (NAPE) precursors by the phosphodiesterase NAPE-PLD, and (2) double O-deacylation of NAPEs followed by phosphodiester bond hydrolysis of the resulting glycero-phospho (GP)-NAEs. We recently identified GDE1 as a GP-NAE phosphodiesterase that may be involved in the second pathway. Here, we report the generation and characterization of GDE1(-/-) mice, which are viable and overtly normal in their cage behavior. Brain homogenates from GDE1(-/-) mice exhibit a near-complete loss of detectable GP-NAE phosphodiesterase activity; however, bulk brain levels of AEA and other NAEs were unaltered in these animals. To address the possibility of compensatory pathways, we generated GDE1(-/-)/NAPE-PLD(-/-) mice. Conversion of NAPE to NAE was virtually undetectable in brain homogenates from these animals as measured under standard assay conditions, but again, bulk changes in brain NAEs were not observed. Interestingly, significant reductions in the accumulation of brain NAEs, including anandamide, were detected in GDE1(-/-)/NAPE-PLD(-/-) mice treated with a fatty acid amide hydrolase (FAAH) inhibitor that blocks NAE degradation. Finally, we determined that primary neurons from GDE1(-/-)/NAPE-PLD(-/-) mice can convert NAPEs to NAEs by a pathway that is not preserved following cell homogenization. In summary, combined inactivation of GDE1 and NAPE-PLD results in partial disruption of NAE biosynthesis, while also pointing to the existence of an additional enzymatic pathway(s) that converts NAPEs to NAEs. Characterization of this pathway should provide clarity on the multifaceted nature of NAE biosynthesis.Molecular BioSystems 08/2010; 6(8):1411-8. DOI:10.1039/c000237b · 3.35 Impact Factor
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ABSTRACT: Genome sequencing projects have uncovered thousands of uncharacterized enzymes in eukaryotic and prokaryotic organisms. Deciphering the physiological functions of enzymes requires tools to profile and perturb their activities in native biological systems. Activity-based protein profiling has emerged as a powerful chemoproteomic strategy to achieve these objectives through the use of chemical probes that target large swaths of enzymes that share active-site features. Here, we review activity-based protein profiling and its implementation to annotate the enzymatic proteome, with particular attention given to probes that target serine hydrolases, a diverse superfamily of enzymes replete with many uncharacterized members.Journal of Biological Chemistry 02/2010; 285(15):11051-5. DOI:10.1074/jbc.R109.097600 · 4.60 Impact Factor
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ABSTRACT: Obesity is a worldwide epidemic, and severe obesity is a risk factor for many diseases, including diabetes, heart disease, stroke, and some cancers. Endocannabinoid system (ECS) signaling in the brain and peripheral tissues is activated in obesity and plays a role in the regulation of body weight. The main research question here was whether quantitative measurement of plasma endocannabinoids, anandamide, and related N-acylethanolamines (NAEs), combined with genotyping for mutations in fatty acid amide hydrolase (FAAH) would identify circulating biomarkers of ECS activation in severe obesity. Plasma samples were obtained from 96 severely obese subjects with body mass index (BMI) of > or = 40 kg/m(2), and 48 normal weight subjects with BMI of < or = 26 kg/m(2). Triple-quadrupole mass spectroscopy methods were used to measure plasma ECS analogs. Subjects were genotyped for human FAAH gene mutations. The principal analysis focused on the FAAH 385 C-->A (P129T) mutation by comparing plasma ECS metabolite levels in the FAAH 385 minor A allele carriers versus wild-type C/C carriers in both groups. The main finding was significantly elevated mean plasma levels of anandamide (15.1+/-1.4 pmol/ml) and related NAEs in study subjects that carried the FAAH 385 A mutant alleles versus normal subjects (13.3+/-1.0 pmol/ml) with wild-type FAAH genotype (p = 0.04), and significance was maintained after controlling for BMI. Significantly increased levels of the endocannabinoid anandamide and related NAEs were found in carriers of the FAAH 385 A mutant alleles compared with wild-type FAAH controls. This evidence supports endocannabinoid system activation due to the effect of FAAH 385 mutant A genotype on plasma AEA and related NAE analogs. This is the first study to document that FAAH 385 A mutant alleles have a direct effect on elevated plasma levels of anandamide and related NAEs in humans. These biomarkers may indicate risk for severe obesity and may suggest novel ECS obesity treatment strategies.PLoS ONE 01/2010; 5(1):e8792. DOI:10.1371/journal.pone.0008792 · 3.53 Impact Factor
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ABSTRACT: Two proteomic methods were recently introduced to globally map proteolytic cleavage events in biological systems, one that characterized proteolyzed proteins by differential gel migration (PROTOMAP) and the other by enzymatic tagging and enrichment of the nascent N-terminal peptides generated by proteolysis (Subtiligase). Both technologies were applied to apoptosis, and each uncovered hundreds of novel proteolytic events. An initial survey, however, revealed only minimal overlap in the two data sets. In this article, we perform an in-depth comparative analysis of the PROTOMAP and Subtiligase results that assimilates the complementary information acquired by each method. This analysis uncovered substantial agreement between the PROTOMAP and Subtiligase data sets, which in integrated form yield a highly enriched portrait of the proteome-wide impact of proteolysis in apoptosis. We discuss the respective strengths of each proteomic method and the potential for these technologies to expand the scope and sensitivity of large-scale studies of proteolysis in biological systems.ACS Chemical Biology 06/2009; 4(6):401-8. DOI:10.1021/cb900082q · 5.44 Impact Factor
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ABSTRACT: As the field of chemical biology matures, its practitioners are tackling ever more sophisticated biological problems. Chemical approaches, both synthetic and analytical, provide researchers with powerful new technologies to perturb, dissect and even reconstruct complex biological systems. Here we discuss the special challenges and opportunities confronted at the burgeoning interface of chemical and systems biology.Nature Chemical Biology 12/2008; 4(11):639-42. DOI:10.1038/nchembio1108-639 · 12.95 Impact Factor
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ABSTRACT: Proteolysis is a key regulatory process that promotes the (in)activation, translocation, and/or degradation of proteins. As such, there is considerable interest in methods to comprehensively characterize proteolytic pathways in biological systems. Here, we describe a robust and versatile proteomic platform that enables direct visualization of the topography and magnitude of proteolytic events on a global scale. We use this method to generate a proteome-wide map of proteolytic events induced by the intrinsic apoptotic pathway. This profile contained 91 characterized caspase substrates as well as 170 additional proteins not previously known to be cleaved during apoptosis. Surprisingly, the vast majority of proteolyzed proteins, regardless of the extent of cleavage, yielded persistent fragments that correspond to discrete protein domains, suggesting that the generation of active effector proteins may be a principal function of apoptotic proteolytic cascades.Cell 09/2008; 134(4):679-91. DOI:10.1016/j.cell.2008.06.038 · 31.96 Impact Factor
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ABSTRACT: Insights into the proteome reactivity of electrophiles are crucial for designing activity-based probes for enzymes lacking cognate affinity labels. Here, we show that different classes of carbon electrophiles exhibit markedly distinct amino acid labeling profiles in proteomes, ranging from selective reactivity with cysteine to adducts with several amino acids. These data specify electrophilic chemotypes with restricted and permissive reactivity profiles to guide the design of next-generation functional proteomics probes.Nature Chemical Biology 08/2008; 4(7):405-7. DOI:10.1038/nchembio.91 · 12.95 Impact Factor
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ABSTRACT: Delta(9)-tetrahydrocannabinol (THC), the psychoactive ingredient of marijuana, has useful medicinal properties but also undesirable side effects. The brain receptor for THC, CB(1), is also activated by the endogenous cannabinoids anandamide and 2-arachidonylglycerol (2-AG). Augmentation of endocannabinoid signaling by blockade of their metabolism may offer a more selective pharmacological approach compared with CB(1) agonists. Consistent with this premise, inhibitors of the anandamide-degrading enzyme fatty acid amide hydrolase (FAAH) produce analgesic and anxiolytic effects without cognitive defects. In contrast, we show that dual blockade of the endocannabinoid-degrading enzymes monoacylglycerol lipase (MAGL) and FAAH by selected organophosphorus agents leads to greater than ten-fold elevations in brain levels of both 2-AG and anandamide and to robust CB(1)-dependent behavioral effects that mirror those observed with CB(1) agonists. Arachidonic acid levels are decreased by the organophosphorus agents in amounts equivalent to elevations in 2-AG, which indicates that endocannabinoid and eicosanoid signaling pathways may be coordinately regulated in the brain.Nature Chemical Biology 07/2008; 4(6):373-8. DOI:10.1038/nchembio.86 · 12.95 Impact Factor
Article: Anandamide biosynthesis catalyzed by the phosphodiesterase GDE1 and detection of glycerophospho-N-acyl ethanolamine precursors in mouse brain.[Show abstract] [Hide abstract]
ABSTRACT: Anandamide (AEA) is an endogenous ligand of cannabinoid receptors and a well characterized mediator of many physiological processes including inflammation, pain, and appetite. The biosynthetic pathway(s) for anandamide and its N-acyl ethanolamine (NAE) congeners remain enigmatic. Previously, we proposed an enzymatic route for producing NAEs that involves the double-O-deacylation of N-acyl phosphatidylethanolamines (NAPEs) by alpha/beta-hydrolase 4 (ABDH4 or Abh4) to form glycerophospho (GP)-NAEs, followed by conversion of these intermediates to NAEs by an unidentified phosphodiesterase. Here, we report the detection and measurement of GP-NAEs, including the anandamide precursor glycerophospho-N-arachidonoylethanolamine (GP-NArE), as endogenous constituents of mouse brain tissue. Inhibition of the phosphodiesterase-mediated degradation of GP-NAEs ex vivo resulted in a striking accumulation of these lipids in brain extracts, suggesting a rapid endogenous flux through this pathway. Furthermore, we identify the glycerophosphodiesterase GDE1, also known as MIR16, as a broadly expressed membrane enzyme with robust GP-NAE phosphodiesterase activity. Together, these data provide evidence for a multistep pathway for the production of anandamide in the nervous system by the sequential actions of Abh4 and GDE1.Journal of Biological Chemistry 05/2008; 283(14):9341-9. DOI:10.1074/jbc.M707807200 · 4.60 Impact Factor
Article: Localization ofN-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) expression in mouse brain: A new perspective onN-acylethanolamines as neural signaling molecules[Show abstract] [Hide abstract]
ABSTRACT: N-acylethanolamines (NAEs) are membrane-derived lipids that are utilized as signaling molecules in the nervous system (e.g., the endocannabinoid anandamide). An N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) that catalyzes formation of NAEs was recently identified as a member of the zinc metallohydrolase family of enzymes. NAPE-PLD(-/-) mice have greatly reduced brain levels of long-chain saturated NAEs but wild-type levels of polyunsaturated NAEs (e.g., anandamide), suggesting an important role for NAPE-PLD in the biosynthesis of at least a subset of endogenous NAEs in the mammalian nervous system. To provide a neuroanatomical basis for investigation of NAPE-PLD function, here we have analyzed expression of NAPE-PLD in the mouse brain using mRNA in situ hybridization and immunocytochemistry. NAPE-PLD(-/-) mice were utilized to establish the specificity of probes/antibodies used. The most striking feature of NAPE-PLD expression in the brain was in the dentate gyrus, where a strong mRNA signal was detected in granule cells. Accordingly, immunocytochemical analysis revealed intense NAPE-PLD immunoreactivity in the axons of granule cells (mossy fibers). Intense NAPE-PLD immunoreactivity was also detected in axons of the vomeronasal nerve that project to the accessory olfactory bulb. NAPE-PLD expression was detected in other brain regions (e.g., hippocampus, cortex, thalamus, hypothalamus), but the intensity of immunostaining was weaker than in mossy fibers. Collectively, the data obtained indicate that NAPE-PLD is expressed by specific populations of neurons in the brain and targeted to axonal processes. We suggest that NAEs generated by NAPE-PLD in axons may act as anterograde synaptic signaling molecules that regulate the activity of postsynaptic neurons.The Journal of Comparative Neurology 02/2008; 506(4):604-15. DOI:10.1002/cne.21568 · 3.51 Impact Factor
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ABSTRACT: In the past decade, there have been remarkable advances in proteomic technologies. Mass spectrometry has emerged as the preferred method for in-depth characterization of the protein components of biological systems. Using mass spectrometry, key insights into the composition, regulation and function of molecular complexes and pathways have been gained. From these studies, it is clear that mass-spectrometry-based proteomics is now a powerful 'hypothesis-generating engine' that, when combined with complementary molecular, cellular and pharmacological techniques, provides a framework for translating large data sets into an understanding of complex biological processes.Nature 01/2008; 450(7172):991-1000. DOI:10.1038/nature06525 · 42.35 Impact Factor
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- Nature Chemical Biology (4)
- Journal of Biological Chemistry (2)
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- Nature (2)
- PLoS ONE (2)
Abide TherapeuticsSan Diego, California, United States
The Scripps Research Institute
La Jolla, CA, United States
- • Department of Chemical Physiology
- • Skaggs Institute for Chemical Biology
- • Department of Chemistry


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Latest Bacterial diseases Reference Libraries
Vibrio vulnificus is a species of Gram-negative, motile, curved, rod-shaped bacteria of the Vibrio Genus. Hollis et al. first reported it in 1976. It was given the name Beneckea vulnifica by Reichelt et al. in 1976 and in 1979 Vibrio vulnificus by Farmer. V. vulnificus is related to V. cholerae and is present in marine environments such as estuaries, brackish ponds, or coastal areas. It causes an infection often incurred after eating seafood, especially raw or undercooked oysters. It can...
Vibrio cholerae is a gram negative comma-shaped bacterium with a polar flagellum that causes cholera in humans. V. cholerae belongs to the gamma subdivision of the Proteobacteria. Classical and El Tor are the two types of V. Cholerae identified by hemaggluttination testing. El Tor is found throughout the world, while the classical biotype is found only in Bangladesh. It was first isolated as the cause of cholera by Italian anatomist Filippo Pacini in 1854; however, this discovery was not...
Streptococcus pyogenes is a spherical, Gram-positive bacterium is the cause of Group A streptococcal infections. It displays streptococcal group A antigen on its cell wall. When it is cultured on blood agar plates it produces large zones of beta-hemolysis. They are catalase-negative and in ideal conditions it has an incubation period of about 1-3 days. It is an infrequent part of the skin flora. It is the cause of many important human diseases, ranging from mild superficial skin infections...
Staphylococcus aureus is a facultative anaerobic gram-positive coccus, and is the most common cause of staph infections. It is commonly part of the skin flora found in the nose and on skin. Around 20% of the human population is long-term carriers. It gets its golden color due to its carotenoid pigment staphyloxanthin. The pigment acts as a virulence factor with an antioxidant action that allows the microbe to evade death by reactive oxygen species used by the host immune system. Staphylococci...
Rickettsia rickettsii is a gram-negative bacterium native to the New World and causes the malady known as Rocky Mountain spotted fever (RMSF). It is transmitted through the bit of an infected tick when it feeds on animals and humans. Humans are not necessary hosts in the rickettsia-tick life cycle but they can be. S. Burt Wolbach created the first detailed description of the etiologic agent in 1919. He recognized it as an intracellular bacterium seen most frequently in endothelial cells....
- Forsooth! indeed! originally a parenthetical phrase used in repeating the words of another with more or less contempt or disdain.


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For over a century, the UBC Debate Society has been a lively, competitive club dedicated to the art of debating and persuasive speaking. We offer students a wide variety of debating experiences, ranging from the casual 'once-in-a-while' speaker to the internationally competitive debater.
Your UBCDS experience is really what you make of it. In addition to offering an abundance of training resources, opportunities to practice, memorable (and subsidized!) competitions, we are both very social and inclusive.
Our regular meetings for second term start on January 9th and are held on Tuesdays at 5pm (in BUCH D317) and Fridays at 4pm (in ANGU 343).
To find out more about joining our club, check out our Join page!


text: Jaxon to Jazmyn: 'I Love You' (Video) by jbz 5/01/2014 | 6:28 8 Posted in News @justinbieber: Awwww.. WATCH VIDEO: Tags:cute, jaxon bieber, jazmyn bieber, jazzy bieber Related Bieber News Justin Bieber Hides Behind MTV Trophies! Happy Holidays! Justin Bieber Spending Christmas with Family in Canada! Justin Bieber with a Cute Puppy! -PIC Justin Bieber: 'Happy Birthday @JaxonBieber, I Love You' Comments Hannah Bieber 6/01/2014 | 10:33 awwww there so cute <3 i love justin...... 6/01/2014 | 10:50 @ Hannah Bieber justin retired!!!!!! Don't know if it's true but, I'm seriously emotional right now!!!!!! Please be a rumor….. Justinbieberfan 7/01/2014 | 7:13 Don't worry he will never quit music he is just taking a break Nicole 7/01/2014 | 1:59 Awwww that was Soooo Cute!!!!!. that's just adorable essie j 7/01/2014 | 6:32 they're so cute aw nicki 7/01/2014 | 2:14 Awww that is so cute…..Luv you guys ♥belieber&jelenator♥ 8/01/2014 | 8:11 aww they are so cute !!!!!!!!!! Belieber 8/01/2014 | 4:41 Aww they're so cute


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Comment: Re:Cannot take attendance? (Score 1) 167
Reminds me of a South Park episode, 'Taming Strange', where they computerize the entire school:
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Reminds me of a South Park episode, 'Taming Strange', where they computerize the entire school:
But putting a giant toaster in your basement to then circulate the heat around? I'm pretty much certain the laws of thermodynamics would say that's a terrible way of doing it.
No less efficient than any other central heating system.
For central heating, the existing solutions would work far better than inefficient electrical appliances generating hear.
There is no such thing as an inefficient electrical heater, unless you're venting the heat outside or something. Because all the waste energy is given off as.. more heat. Plus the heat given off by these appliances is free, since the server company is paying for it.
Free heat
It's hard to beat
Even with forced air
It works a treat
We need coal to be GONE.
We're working on it as fast as we can.
A disturbing trend I've seen is the tendency for a conference or publication to ask the author's recommendation for suitable people to peer review the paper! This largely defeats the purpose of the review, since the author can cherry pick reviewers he knows will vote to accept. Say, a colleague or associate. I don't think the "cherry picking" isn't even conscious most of the time. I mean, who else would you recommend? Someone you don't know?
The justification given by the publisher is that they need someone with the right expertise to correctly review the paper, since it may deal with extremely specialized knowledge. But I've found that asking authors for "peers" seems to be the default for many journals, rather than the exception. So you end up with these low-quality journals that boast a full peer review process, but seem to be full of papers of dubious quality.
But in the publish-or-perish world, any publication is better than no publication, so these journals persist, soaking up rejected papers or low-quality work.
There's an optimal pricing for most services. Take cable TV - lower the price and a few more people will buy in. But, not enough to make up for the lost revenue from lower prices. Raise the prices and you'll get more money, but not enough to make up for the people leaving your service. Your pricing can deviate around that "sweet spot", but not by a huge amount.
That's why companies instead try to make their services shittier, by inserting ads and reducing quality and so forth. People are more willing to put up with that. But if you legislate that they can no longer provide shitty service, it doesn't necessarily mean the prices will increase accordingly. Even if ISPs start lowering their data caps, people will likely perceive that as "paying more for less".
I can't help but see this as anything but a win for the consumer.
would of easily had enough time in the billions of years that have passed to colonize every single planet a thousand times over in the entire galaxy
I take the more pessimistic view: it means that interstellar travel is so difficult that no species has ever managed it.
We cannot build a computer that can model a bug's brain activity
True, but we can create machines that can more or less do what insects can do. Look at self-driving cars: they can make simple maps of their environments, recognize multiple pre-programmed objects (signs, other cars, pedestrians), and navigate around easy obstacles. If we were able to control a beetle with a couple hundred kilograms of computer hardware and sensors, we could probably come up with something roughly similar to what the beetle already does.
Delayed gratification is not about increasing the amount of work you do, it's about being able to plan ahead. I saved up my dollars from a summer job working on my Dad's farm, and bought a computer for $1400 at the end of it. My brother spent his money as soon as he got it, but when I got a computer he wanted one too. So he got some kind of 'lease to own' deal, which he was still paying back years later, long after that thing was an obsolete piece of shit. Ended up costing him almost three grand.
Who ended up working more? This is not a trick question.
The only thing delaying gratification achieves is that you get less years and less opportunity to be happy.
The opposite is true. The ability to save money, to be financially responsible, and to study for an education all reduce the amount of work you need to do over your lifetime. And it will tend to be more enjoyable, satisfying work.
Torrents... I see what you did there.
It all depends on how long you've been playing. (And how long you've been reading spoilers) For those who play for conducts, the most common conducts are:
Never changed shape.
Never polymorphed an item.
Never wished for an artifact item.
Never wished for a regular item.
So you see lots of five-conduct ascensions, since these five are relatively easy to achieve. Easier than say, weaponless. Or pacifist.
(Seriously-- Gehenna without any genocide scrolls? LOL! As IF!)
Heh. I'm guessing this is about arch-liches. They're dangerous, but manageable if you have magic resistance. You just stand on the upstairs and beat them to
... though his invention worked superbly -- his theory was a crock of sewage from beginning to end. -- Vernor Vinge, "The Peace War"


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COP18 Hotcoldwetdry Talks Pretty Much End In Failure
Except for those who enjoyed their government funded working vacation, of course. They had a great time…..well, eating, since no alcohol is allowed in the Muslim nation of Qatar. As for the talks themselves, really, when you hold them in the world's 3rd highest "Carbon polluting" nation, it's no wonder they failed. (Reuters) gives it the old college try in trying to rescue the outcome
Almost 200 nations extended a weakened United Nations plan for combating global warming until 2020 on Saturday with a modest set of measures that would do nothing to halt rising world greenhouse gas emissions.
Many countries and environmentalists said the deal at the end of marathon two-week U.N. talks in OPEC-member Qatar would fail to slow rising temperatures or avert more floods, droughts, heatwaves and rising sea levels. (hey, look, hotcoldwetdry!)
Environment ministers extended until 2020 the Kyoto Protocol, which obliges about 35 industrialised nations to cut their greenhouse gas emissions until the end of 2012. That keeps the pact alive as the sole legally binding climate plan.
Problem is, only 37 countries of 194 actually signed on to the extension of Kyoto. Many others offer a non-binding "declaration of intent." Canada, New Zealand, Russia, and even Japan, the nation for which the original protocol was conceived, opted out. For those who committed, that only covers 15% of mankind's CO2 output.
They did agree to
steal raise around $100 billion dollars in aid for developing nations, but there is no framework nor is there any binding commitment to do so.
Britain was a big force in pushing the extension and binding themselves to hosing their economy even more with "green" targets and spending billions. Um, yeah
More snow is expected to fall in the south east (of Britain) from Monday as bitterly cold north-easterly winds continue to bring temperatures as low as 14F (-10C), icy roads and freezing fog.
My bad, I forgot that now cold weather is caused by heat trapping gases.
Fortunately for climate partiers, this means that there will be more United Nations meetings in luxuries vacations spots in future years, where they can talk to their hearts content about reducing Other People's carbon footprints before jumping back in their fossil fueled airplanes. For COP19, it will be in an Eastern Europe nation, to be decided by whomever provides the best party atmosphere, and which will be amusing as hell, since Eastern Europe has had 4 straight miserable winters, with very cold temps and lots of winter weather.
Crossed at Pirate's Cove. Follow me on Twitter @WilliamTeach.
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It took a lot of guts to do what this young man did. They also offered him 20k in hush money. Fabulous. The proof in my opinion here is that...Read More
William Teach
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Comfort Inn Near Plano Medical Center, Plano
Situated in the heart of Plano, Comfort Inn Near Plano Medical Center is close to Shops at Willow Bend. Additional area attractions include University of Texas at Dallas and Arbor Hills Nature Preserve.
Hotel Features.
Wireless and wired high-speed Internet access is complimentary in public areas. Business amenities include a business center and a meeting room. A complimentary breakfast is available. Additional amenities include a 24-hour fitness center, multilingual staff, and coffee/tea in the lobby. Complimentary self parking is available onsite for guests. This is a smoke-free property.
The 65 air-conditioned guestrooms at Comfort Inn Near Plano Medical Center include coffee/tea makers and hair dryers. Complimentary wireless and wired high-speed Internet access is provided. Televisions are equipped with premium cable channels. All accommodations provide desks and phones; free local calls are offered (restrictions may apply). All units feature microwaves and refrigerators. Additional amenities include irons/ironing boards and complimentary toiletries. Housekeeping is offered daily. Renovation of all guestrooms was completed in October 2014.
old hotel. Not as nice as most Comfort Inn we've stayed at. Will not do stay again.
The only problem with the was the shower curtain rod was broken and you could not keep…
Enter dates to check prices
Hotel Info: 866-539-8117from $86
- Standard Doubles
- Standard Room, 1 King Bed with Sofabed, Non Smoking
- Standard King
- Standard Room, 2 Queen Beds, Non Smoking
Recommended hotels
At a glance
Key facts
Hotel size
- This hotel has 65 rooms
- This hotel is arranged over 2 floors
- Check-in time 3 PM-7 AM
- Check-out time is 11 AM
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
- Children (18 years old and younger) stay free when occupying the parent or guardian's room, using existing bedding
- Pets not allowed
- Free WiFi and wired Internet access in public areas
- Free WiFi and wired Internet access in rooms
- Free self parking
Other information
- Smoke-free property
Nearby Two Star Plano hotels
In the hotel
- Free buffet breakfast
- Coffee/tea in the lobby
- 24-hour fitness facilities
- Business center
- One meeting room
- 24-hour front desk
- Dry cleaning/laundry service
- Free newspapers in lobby
- Number of buildings/towers - 1
- Elevator/lift
- Safe-deposit box at front desk
- In-room accessibility
In the room
- Air conditioning
- Coffee/tea maker
- Iron/ironing board
- Free toiletries
- Hair dryer
- Premium TV channels
- Desk
- Free WiFi
- Free local calls
- Refrigerator
- Microwave
- Daily housekeeping
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"Hotel management and staff were wonderful...professional, friendly, and accommodating. Lobby/bar/lounge area is very nice and the entire hotel is spotless. We plan to go back and…"Mar 8, 2015


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...I also recognize which advisors were able to help me and which ones were not. In turn, I've learned how to be patient while remaining resolute in jointly pursuing a scholastic goal. Lastly, I am in a perfect position to sympathize with the challenges facing students, as I myself continue to take post-graduate coursework in and draft scholarly articles in English Literature.
58 Subjects: including Latin, English, reading, writing
Los Angeles, CA
I am a second year PhD student in the History Department at UCLA. My specific field of interest is Ancient Mediterranean History, as well as the languages of Ancient Greek and Latin. I have multiple years of tutoring experience with students of all ages and levels.
3 Subjects: including Latin, Greek, classics
Los Angeles, CA
...In 2007, I was an instructor at Salpointe Catholic High School (History, 10th and 11th grades). From the Fall of 2008 to the Spring of 2010 I was a Latin instructor at the University of Arizona. I am currently teaching first-year Latin at UCLA.I have studied Latin for over a decade and I have ex...
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...I am able to tutor students in these skills when working with literature of other time periods and cultures, as well. I am a voracious reader and I have read a huge amount of English literature, as well as foreign literature translated into English and ancient Greek and Roman literature, both in...
19 Subjects: including Latin, reading, English, GRE
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...I studied abroad for a semester in Rome. I am a current PhD student of Classics at UCLA and my specific focus is on Ancient Greek Literature. I learned Ancient Greek at Georgetown University, where I studied it for 4 years and received a BA in Classical Languages.
6 Subjects: including Latin, algebra 1, Italian, prealgebra
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Questions - Glass on Glass Mosaics.
Hello all. I've been lurking and enjoying your beautiful artwork for sometime now, and I also browse the garden junk forum as well.
I am not exactly new to glass, I own a kiln, and have dabbled in fused glass, but lately I have a new obsession and that is taking all that old glass and gluing it. I think I've enjoyed gluing things all over things since I was about two. I just recently realized there's a name for it, mosaics!
Mostly, I want to know how mandalas or glass folding tables are made. Is it a special glass? Tempered glass? I would think if I were to just cut a sheet of clear glass and start mosaicing it would be so easy to break. How do you make something strong enough to hold up yet hang in a window or go on top of a table? I want the light to show through, so wouldn't want to use an MDF or backerboard substrate.
Any suggestions would be so much appreciated. Thank you for a great place to come and admire and be inspired!
Welcome to a great playground, BEANY. I'll let those w/experience advise you, but if I were going to mosaic a glass top table, I'd use 1/4" plate glass for the substrate. One of my patio tables has a glass top, and I've been thinking of mosaicing it for some time. IMO, it w/not be easily broken. FLAG can tell you a little story about an accident w/a GOG table top, and the amazing strength it showed when it fell to a concrete floor. I think most of the glass on glass (GOG) artists here prefer Mac glue or GEII as an adhesive.
I'm thinking maybe a microwave turntable for a mandala, but not sure how to find those either...but the glass tables, even the folding ones with tempered glass are usually expensive. Maybe I'll have to pay closer attention to thrift stores and garage sales etc. I'm just not artistically ready for that kind of investment yet. Thanks for the tip on the Mac Glue or GEII silicone.
I used a microwave turntable for a little table from my bro. Used a large ceramic pot for its base. By all means, check Salvation Army, Goodwill - all thrift stores. I've seen them available there.
Microwave turntable
Hi Beany! Welcome to the Obsession of GOG!!!heh heh! I LOVE doing GOG and anything is Fair Game!!! I have used the mirror door of a shower door set, 1/4glass, tabletop glass, old wooden windows, Plexiglass tubes(ice bucket) old outdoor plexiglass globes,
Wow, beautiful stuff. I asked on freecycle.org and got a glass microwave plate and going to try hitting the thrift stores this week to see if I can get some more. This one has a built in pattern on it which might be a little harder to do than if it was flat, but still, I love it! Thanks so much for sharing!
Calamity how were you able to hang the one I see here with the bird house? Drilling slowly with water and a diamond bit?
Yup, I think I used a diamond bit and a sponge for keeping water around the bit when drilling. Haven't tried drilling a microwave plate as of yet, I know that some things are tempered and may explode/break apart when drilled. I was going to also mention that all the glass used on that bird house one, is scrounged old 70's stained glass, that I find at thrift stores/garage sales/for sale by owner websites...so I probably don't spend very much on my projects, I spend money on the marine silicone and outdoor grout and sealer I use as I want it to last(I use thinset when I can)
Calamity, I found six cobalt blue saucers at a thrift shop. I wanted to use blue on the last guitar I made so I got one of the saucers and nipped it with the wheeled nippers (as I have done a thousand times before). The saucer EXPLODED all over the porch. It was scary. So guess it wasn't annealed, probably made in China. So be careful out there, people!
Hello all
I have dabbled in other media like oil and acrylic painting, Recently I got interested in
glass tiles / stained glass mosaics (complete newbie). My question is, can I mount
stained glass art work on an acrylic sheet (plexiglass) by using glue? I have searched
several forums and cannot find an answer.
thanks in advance
SilvaMae has the info on her hubpage
Here is a link that might be useful: mosaic on plexiglass


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Speakers Corner
It's free to register, to post a question or to start / join a discussion
I thought they were talking about Africa
Likes # 0
Posted March 30, 2013 at 7:39PM
Honestly I saw this enter link description here and at first it didn't sink in that they were talking about darkest Kent.
If it is true then this country is in a very bad state of affairs.
Likes # 0
Posted March 30, 2013 at 8:21PM
Unfortunately the criminal does not respect country's or respect other peoples rights, all they see is a way to make some money, and they don't care who or what gets hurt.
Why did I think of politicians when I wrote that?
Likes # 0
Posted March 30, 2013 at 9:49PM
I see the story says 'it's impossible to judge what the threat is'.
Still, it is important to let people know about it, especially at the start of a holiday weekend when people will be wondering where to go for a day out.
Likes # 0
Posted March 31, 2013 at 8:13AM
Or Gay Parie
Likes # 0
Posted March 31, 2013 at 9:14AM
Meanwhile, the fight against real poachers claims five lives.
Likes # 0
Posted March 31, 2013 at 9:20AM
"Their horns are sold in Asia, where some believe they have medicinal purposes, although there is no evidence to support it."
You'd think that wealthy Asians would have the brains to buy the best western medical cures rather than believe in witch doctor remedies in the 21st century.
Likes # 0
Posted March 31, 2013 at 10:11AM
That's an interesting comment to make today of all days.
Likes # 0
Posted March 31, 2013 at 10:32AM
At least here in a UK or possibly any other enclosed wildlife park, the chance of survival would be far higher, than out in the bush in Africa or other 'supposedly protected' free ranging wildlife area.
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