ernas

Human breast cancer cell. Image courtesy of the National Cancer Institute.

Enhancer RNAs Alter Gene Expression
New class of molecules may be key emerging “enhancer therapy”

In a pair of distinct but complementary papers, researchers at the University of California, San Diego School of Medicine and colleagues illuminate the functional importance of a relatively new class of RNA molecules. The work, published online this week in the journal Nature, suggests modulation of “enhancer-directed RNAs” or “eRNAs” could provide a new way to alter gene expression in living cells, perhaps affecting the development or pathology of many diseases.

Enhancers are sequences in the genome that act to boost or “enhance” the activity or expression of nearby genes. They “often behave in a cell-specific manner and play an important role in establishing a cell’s identity and functional potential,” said Christopher Glass, MD, PhD, a professor in the department of Medicine and Cellular and Molecular Medicine at UC San Diego and principal investigator of one of the papers.

Although enhancers have been recognized for more than 25 years, scientists have labored to fully flesh out the breadth and complexity of what enhancers do and how they do it. In 2010, it was discovered that enhancers directed expression of RNA on a broad scale in neurons and macrophages, a type of immune system cell. Dubbed eRNAs, they were different from other classes of nuclear non-coding RNAs, and raised new questions about their potential roles in the functions of enhancers. The two Nature papers attempt to answer some of these questions.

In the first, principal investigator Glass and colleagues investigated a pair of related transcriptional repressors called Rev-Erb-alpha and Rev-Erb-beta (proteins with important roles in regulating the circadian rhythm in many cell types) in mouse macrophages. Using genome-wide approaches, they found that the Rev-Erb proteins repressed gene expression in macrophages primarily by binding to enhancers. Collaboration with researchers at the Salk Institute for Biological Studies revealed that the repressive function of Rev-Erbs was highly correlated with their ability to repress the production of eRNAs. 

In the second paper, principal investigator Michael G. Rosenfeld, MD, a professor in the UC San Diego Department of Medicine and Howard Hughes Medical Institute investigator, and colleagues looked at estrogen receptor binding in human breast cancer cells – and its impact on enhancer transcription.  In contrast to the repressive functions of Rev-Erbs, estrogen receptors (ERs) activate gene expression; but, like Rev-Erbs, they primarily function by also binding to enhancers. ER binding was shown to be associated with increases in enhancer-directed eRNAs in the vicinity of estrogen-induced genes, and to exert roles on activation of coding target genes.

Both papers offer new evidence that eRNAs significantly contribute to enhancer activity, and therefore to expression of nearby genes. “Because many broadly expressed genes that play key roles in essential cellular functions are under the control of cell-specific enhancers, the ability to affect enhancer function by knocking down eRNAs could potentially provide a new strategy for altering gene expression in vivo in a cell-specific manner,” said Glass, noting that in his research, anti-sense oligonucleotides were developed in conjunction with Isis Pharmaceuticals, which suppressed enhancer activity and reduced expression in nearby genes.

Photo By:  Ikram N'gadi

“Can we just stand idly by and watch while they drown on their way to freedom? We simply can’t. Should we be out at sea, searching and rescuing? Some people say we shouldn’t. And maybe they are right. But as long as people are suffering at sea we have a very good reason to be here. As a doctor and aid worker, this is my duty.”

MSF doctor and emergency team member Erna Rijnierse shares her experiences on an MSF search-and-rescue boat in the Mediterranean. http://bit.ly/1dpT2z3 

2

banana chai ginger brazil nut milk,
made from the scratch - inspired by a smoothie of erna und kaethe.

soak 2 cups of raw brazil nuts in water over night, rinse,
blend in high speed blender with 2 cups of fresh water, strain.
(keep nut meal for other recipes like cakes or crumbles).

brew 2 cups of chai tea, let it cool down.

blend brazil nut milk, chai tea, 2-3 frozen bananas,
dates (to taste - they add full-bodied, sirupy sweetness) and
ginger (to taste - it adds a tangy, citrussy sharpness),
add cardamom and cloves (to taste - they add a fragrant, earthy spiceyness).

ENJOY!

“The SILENCE of the Lambs” Introducing The Power of Uncoded RNA

“The SILENCE of the Lambs” Introducing The Power of Uncoded RNA

An illustration of the central dogma of molecular biology annotated with the processes ncRNAs are involved in. (Photo credit: Wikipedia)

X-ray structure of the tRNA Phe from yeast. Data was obtained by PDB 1ehz and rendered with PyMOL. violet: acceptor stem wine red: D-loop blue: anticodon loop orange: variable loop green: TPsiC-loop yellow: CCA-3′ of the acceptor stem grey: anticodon (Photo…

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7 Years

ладно, вру. 3. если не больше. 3 года ожиданий и надежд увидеть и услышать это вживую..

это была первая метал группа, которая крепко засела мне в душу. примерно 7 лет назад я услышал одну их песню, лишь 5 лет назад я скачал их альбомы, а 3 года назад до меня вдруг дошло, что есть еще и такая вещь как концерты и тут же появилась мечта. а сегодня она осуществилась.

он выходит на сцену, точь-в-точь такой же, каким я видел его на картинках, с неповторимой улыбкой. Старина Салли - простой парень из Бостона, для которого единственной отдушиной в детстве были замусоленные кассеты Black Sabbath и старенький магнитофон в темноте подвала. Который не умел петь абсолютно, но стал обладателем неподражаемого вокала. человек, который стал для меня символом целеустремленности. не всякие там бизнесмены и т.д. а тот, кто шел к в простой в общем-то мечте и добился своего.

и если честно - мне плевать, что он там увлекается темной магией, похлеще вуду и прочее. от него весь концерт шла такая волна энергии, полная отдача, что было просто невозможно не ответить тем же. под конец на глаза наворачивались слезы от ощущения счастья и надежды на то, что и он был рад выступать здесь, мы оправдали его ожидания. глупо наверное звучит, но так оно было. Денис тоже сказал, что из всех концертов, на которых он был (а их в общем-то не мало), этот был самый атмосферный в плане отдачи.

не смогу описать словами как это было, такие вещи нужно пережить, пропустить через себя. но как кто-то очень точно подметил, это смахивало на какое-то волшебство, но не с радугой и пони, скорее действительно похожее на темную магию - ты в его власти, полностью, бесповоротно. она обволакивает тебя легкой волной драйва, нет страха и волнения, проблемы ушли куда то далеко, а сам ты растворился в музыке, пока Салли колдует на сцене, все больше увлекая тебя за собой в его мир - мир настоящей магии.
на других концертах меня вгоняло в транс просто от классных запилов и т.п
сейчас же было что-то более глубокое, непостижимое, завораживающее - воистину магия.

поэтому мне хочется высказать “невысказываемое” спасибо Салли Эрна и его группе Godsmack, за все те эмоции, что они дарили мне на протяжении стольких лет, особенно сегодня.

Салли - Карлсон, который живет на моей крыше.
и он обещал вернуться

Hey! Jij daar! Heb je het hele weekend weer zitten denken over alle dingen die je niet hebt gedaan maar wel had willen doen? Dan is dit jouw teken! Morgen is het een nieuwe dag en dat is de dag dat jij gaat leven. Doe wat je nooit eerder durfde. Spreek die vreemde aan. Laat zien dat jij bestaat! (En als het morgen niet lukt is er de dag erna weer een nieuwe dag) (Proberen is soms ook goed genoeg)

The Wicked End (Welcome To Hell) Chapter Ten

Chapter Ten

“People are strange when you’re a stranger/Faces look ugly when you’re alone/
Women seem wicked when you’re unwanted/Streets are uneven when you’re down”

“When you’re strange faces come out of the rain/When you’re strange no one remembers your name/When you’re strange, when you’re strange/When you’re strange”

“People are strange when you’re a stranger/Faces look ugly when you’re alone/
Women seem wicked when you’re unwanted/Streets are uneven when you’re down”

“When you’re strange faces come out of the rain/When you’re strange no one remembers your name/When you’re strange, when you’re strange/When you’re strange, alright, yeah”

“When you’re strange faces come out of the rain/When you’re strange no one remembers your name/When you’re strange, when you’re strange/When you’re strange”

“People Are Strange” by The Doors

Tommy Lee’s POV

Tommy Lee’s POV Meanwhile back in LA, at the White Box Music Recording Studios…..

        A day and a half later after our long ass night of partying with stripers, booze, and drugs at the posh Sapphire Isle Hotel up in the upscale part of LA, I finally managed to get me and Nikki down here at the recording studio to meet up with Vince and Mick, to start getting the ball running on making a new album. We arrived here yesterday morning and somehow just barely made it on time to start work on some new material, me and Nikki had managed to stay here all night trying to come up with some ideas for song lyrics, well after Vince and MIck left for home to go back to their wives and their sober lives. Ever since Vince finally decided to get sober once and for all, it seemed as though as our little group started to become more and more divided into two smaller groups, the boring ones which were Vince and Mick (whom had always been acting like the old man of the group, anyway), and the partiers which were me and Nikki, both professionally and personally. And even though I have done and do my share of drugs, I must say I’m not nearly as bad or into them as much as Nikki is to be quite frank. And when I say not that bad, I mean that I can actually take them or leave them with no questions. I don’t need drugs all the time to make me and my little world content. That’s what I have my music for. As for Nikki, he can deny all he wants to me, the rest of the guys in the band, our friends and family, and our fans that he doesn’t have a problem till he’s blue in the face, but he can’t fool me at all for one second that he doesn’t have a problem. As the saying goes, you can’t bullshit a bullshitter and today was definitely no different or exception from any other day of the week.

       Anyway, after Vince and MIck had finally left for the night after putting in their time on their half of the work on the album, maybe somewhere around eleven or so, me and Nikki were still sitting in the studio; me at my drums, trying to come up with some killer drum parts for the new record, and Nikki on his bass, writing down his parts, while the both us were drinking some Jack Daniels and trying to come up with some ideas for some of the new songs that we had just started working on. We had just finished writing and recording the final touches to Animal In Me, Mother Fucker Of the Year, and had just started putting down and adding some new lyrics to White Trash Circus, that the both of us had collaborated on while back, while doing a brief stint of shows in Japan. It’s when I noticed on this night that Nikki was starting to exhibit some really strange and odd behaviors that were giving him away as an addict, such as nervous twitching of his body, his lack of focus, getting up every fifth teen minutes to just pace back and forth across the room, increase agitation, constant muttering and mumbling to himself, etc. It was all really weird and out of character shit for him, that’s for damn sure.

       “Oh my god, I seriously need a fucking break! My head is just throbbing from all this writing and thinking,” shouted Nikki as he slammed his bass on the table and got up from the table, and started making his way to doorway to head on out of the studio. “I just can’t fucking take this shit anymore.”

        Immediately, I stopped all my drumming after I looked directly up at him and saw how agitated that he was quickly becoming, I immediately got up and ran towards Nikki to see what the hell was going with him by grabbing him firmly by the arm as he was starting to make his way out the door. “Nikki, where the hell are you going? We’re on a fucking good roll tonight. We just finished with Animal In Me and Mother Fucker Of the Year, and just started getting White Trash Circus up and running lyrically. Let’s try to stay on task for just a little longer and finish up with this song, and then we’ll head out of here for the night and go pick up some chicks to keep us busy.”

        “Look, I just need a damn break, man,” snapped Nikki, as he quickly pulled his arm away from me. “I’m in no mood for the company of a woman tonight. I’m just so fucking stressed out, I just need to be alone for a few fucking minutes.” “Whoa, Dude! You need to chill the fuck out and relax a bit,” I said with concern at how quickly tensed Nikki was getting around me, and he never ever got this way at all with me before. This definitely had me concerned and most alarmed about him and his overall mental and physical health. We’ve always been able to just talk about things and laugh at stupid random stuff, and usually NIkki is a super, easy going person to be around, but this Nikki that was standing before me with a serious scowl across his face was not the same happy NIkki from a few years back that I first met. “Is everything alright with you, man?”, I asked him.

        “Look, I’m sorry, Tommy! I don’t mean to be so damn snippy with you,” began Nikki as he just shook his head and relaxed his shoulders a bit and his overall stance. “But I just have so much going on in my life and in my head these days, that it’s leaving me absolutely crazy and frustrated as all hell. Just give me a few minutes to be alone to calm the fuck down and I’ll be right back.”

        Before I could say or do anything to see if I could get him to change his mind and sit down with me right now and deal with whatever the hell is going on in his hand, Nikki quickly turns around and continues walking right on out of the recording studio door. You know, ever since him and his slutty ass ex-wife Donna D'Errico got divorce awhile back, Nikki just hasn’t been himself at all and has really gotten worse and apparently so much on this night. His lyrics for our music have been bad ass, but his bass playing is starting to suffer and his whole general outlook and attitude on life has been extremely shitty as of late. And there was absolutely nothing that I or anyone else could do about it at the moment.

         After about twenty minutes or so after Nikki disappeared from the studio, abandoning the rest his work load, and leaving me hanging around, hoping that he would eventually bring his ass back here to finally get this shit done and over with for the night, I finally grew so damn impatient that I immediately got my ass off the drum kit and proceeded to walk over to the front door and try to hunt him down, to bring him back here and talk things out with him.

       As soon as I walked into the main hallway, all of a sudden, I heard an extremely loud crash and thud sounds, along with some flashing lights coming from the men’s restroom down the hall on my left hand side of me. I immediately ran down the hall towards the bathroom, rushed right on in, and to my complete shock and horror, there was Nikki completely laid out on the floor and knocked out cold with a cracked forehead and blood gushing all over the place. And as he was all laid out and out cold, he was shape shifting into different objects and things faster than a jack rabbit running across the hot, desert sand, while blood was still gushing everywhere.

      “Oh shit! This can’t be fucking good!” I said to myself as I started looking all over the bathroom and noticed that one of the bathroom mirrors was smashed in so bad that you couldn’t even see your reflection anymore, and there were huge shards of glass pieces all over the place. And as I looked all around Nikki and all over the floor, I immediately had spotted a syringe on the floor, that was laying right next to Nikki and had just rolled right underneath one of the bathroom stalls. It was then I just realized what he had just done when he came in here, when he said he needed a break earlier. He fucking shot himself up a dose of heroin, and now he’s fucking overdosing in the men’s room.

    “Nikki, what the hell did you do to yourself, man?” I asked, as I quickly knelt down beside him to check to see if he had a pulse at all, which thank god he did, so I knew he was well alive, but I was still completely freaking the fuck out on the inside. “What kind of trouble are you in and how badly are you hurting, my friend?”

“No, I don’t feel a thing./Life’s going by me. And still I say,/Oh God! I’m making the same mistakes.”

“Low? I’m on empty./Try to erase all the bad times./Free? I don’t seem to be./
My soul remains tied to your life./Every breath you breathe deep, I feel you circulating through me./I’ll never forgive myself again./I’m so sick and tired of making the same mistakes.”

“MIstakes”…..Godsmack

Hailee Bach’s POV

Hailee Bach’s POV Meanwhile, back at the Exalted Galaxy Hotel, in Morristown, New Jersey….

      Once Calista had finally checked out of the hotel earlier this morning to continue on with her venture to California, I quickly summoned Jasmine and Mom to briefly go over a few things that had occurred late last night with Corey and David being here, and how quickly Dad came back to the hotel after he dropped her off here, so he could quickly go get her car towed and fixed for this morning. Luckily, one of them saw Dad, and must of told the other about Dad being down here on Earth and as well as told Sully as well, that they saw him here and seriously hauled some ass before he came back here to the motel to check on Calista. Thankfully, she was safe and sound in her room the remainder of the night, and Dad had immediately called me down from heaven to watch over things here until she woke up and was ready to leave to venture out.

     “Hailee, my girl! How are things down here?”, Mom asked me with all seriousness as her and Jasmine beamed into the motel office directly from heaven.

     “Things are fine now after Dad came back to check on Calista after bringing her car to the nearest tow truck company down the road and quickly managed to scare off Corey and David before anything went down,” I said, with a slight smile on my face and walked over to my sister and mother to give each one a hug before returning to my position behind the counter.

     “Thank goodness for that,” stated Mom with a deep sigh of relief, as she slowly looked around the room and carefully glanced over everything and studied every detail in the room to make sure that there wasn’t anything suspicious laying around anywhere. “Is Calista still here or she’s already gone? And is she alright?”

       “She’s gone. She left about a half an hour ago and is very determined to make it out to Hollywood one way or another. At least, that’s what I had gathered from how quickly she peeled off from the parking lot earlier as if she was an Evil Kneevil stunt woman, doing a semi-donut outside before finally hitting the road,” I said, laughing slightly, as I quickly looked down on the office computer screen in front of me and started to look up a few things that were saved onto the computer data bases from last night’s events. “So to answer your question, mom, Calista is just fine.”

      “At least, the young lady is safe for now from Sully’s creeps,” began Mom, as she rested her left arm on the counter, and leans forward towards me to look at the computer screen as I continued to search through the data bases . “But we need to keep a very close and carefull eye on her at all times. Especially if both Corey and Dave are still on the Earth’s surface, doing all of Sully’s dirty work. I don’t want nothing to happen to that poor, innocent, young girl. Speaking of her, what town is Calista is going to be stopping at next?”

      After a few more minutes of searching through different profiles and several maps that I had access to through the motel’s computer bases and internet, I finally managed to pull up a map of Iowa on the screen and a bright, red blinking light starts flashing over the city of Des Moines. “It looks like she’ll be heading towards Des Moines in the next two or three days,” I said nonchalantly, glancing back up at Mom, who was waiting patiently for my answer while lightly tapping her fingernails on the desk countertop.

        As soon as I even mentioned Des Moines, all of a sudden out of nowhere, I could see Jasmine, who’s standing close behind Mom and near the office front door, immediately starts becoming all flushed red and her eyes rolling into the back of her head as a white, billowy, cloud of smoke starts forming around her and beneath her feet. This always happens when her ESP starts kicking in and has a vision flooding into her head like a ton of bricks at times, especially if it’s a vision that’s about to happen soon in the near future. Not always a pretty picture to always sit and watch, but Jasmine is always spot on and very accurate with how true her visions really become.

         “Honey, what’s wrong? What kind of vision are you having right now?”, asked Mom, with a tone of concern in her voice as she quickly turned around to see Jasmine shaking, convulsing, and foaming at the mouth as if she was having some kind of seizure. I quickly jumped over the counter to reach for her when I noticed how quickly she was dropping to her knees on the floor from having this vision. This is definitely not a good sign of things to come if Jasmine has a vision quite this powerful and has such an affect on her.

    “Jasmine, please wake up! Tell me what you saw!” I said, shouting at her as I’m trying to shake her out of her little haze and snap back into reality and get her to talk to me. After a minute or so of shaking some sense into her, the color of her eyes returned to normal as she finally opened them up to glance right away with a dark concern and grimace look on her face. “What’s wrong, Jasmine? Please tell me.”

       “Their waiting patiently for Calista in Des Moines,” Jasmine says very meekly, as she’s trying to regain her strength to talk and think straight so as she could openly talk to me. “Who’s waiting for Calista in Des Moines? Corey and David?” Mom asks, sounding even more concern, as she comes over to me and Jasmine’s side, and kneels beside me. “What the hell are they planning to do to her?”

         "Yes, and Corey and Dave are going to get to her before you and Dad show up to save her,“ stated Jasmine nervously as she was able to push herself up in a sitting up position on the floor. "Corey is just as an evil bastard as Sully is. He’s planning on raping Calista before he drags her down to hell to bring her to Sully. Corey definitely has some serious and cruel intentions that he’s planning on doing to her, to say the very least of what’s about to happened.”

        “Not if I can help it, that’s for damns sure,” yelled Mom as she quickly jumped back up on her feet quicker than a hiccup, and starts pacing back and forth across the office floor furiously, before returning her attention back to me and Jasmine. “I want you two head on over Des Moines now and follow every single inch and move that Calista makes as she’s heading out to Hollywood, to try to keep her as safe as possible from those two jerks, especially from the likes of one Corey Taylor. I know exactly what that asshole is capable of doing.”

    “What about the elderly couple that’s tied up in the closet, still knocked out cold?”, I asked as I stood up and helped Jasmine to her feet.

     “Don’t worry about them! I’ll take care of them and make sure their alright. You two start making your way to Des Moines now and protect that young girl with all your lives from those two sinister bastards,” said Mom, nonchalantly as she quickly glanced over to the closet that I was pointing to where the elderly couple was still passed out in, before returning her attention back to us. “I’ll get them all settled and then I’m off to go warn your dad about this serious situation that’s starting to brew.”

       With that being said and no questions asked, me and Jasmine quickly teleported out of the hotel with no hesitation and started flying out to Des Moines to save Calista.

Het mooiste cadeau dat je iemand kunt geven is leegte

We ontwaakten in een spel, waren nergens
en naast ons was er helemaal niks. Wij waren het
en de enige. We wisten precies wat ons te doen stond:
zolang we erin slaagden mochten we samen God spelen.

We kenden de verhalen van de oerknal en Darwins theorie
maar hadden het meer op met creationisme.

Dus zorgde jij dat je een potlood schiep en bedacht ik het papier.
We trokken een cirkel, groot genoeg om in te staan.
Vanaf dat moment werd al het elders daar, bevonden wij ons hier.

Iets met tijd, had ik een keer gelezen, dus ik klapte in mijn handen.
Zestig keer en zette een grote, kale muur neer
die ad infinitum mijn klappen zou weerkaatsen.

Je zei: ‘Ook de tijd verdient het dat wij ons erin kunnen plaatsen.’
Je schudde gebeuren uit je mouw en ik zoog bewustzijn uit mijn duim.
Wat plaats zou vinden binnen al het huidige besef, heette nu.
Daarvoor was geweest, erna zou nog komen.

Een niet te bevatten slaap drong zich aan ons op.
We vouwden uit de plooien van onze huiden een bed
en tekenden naast onze cirkel een rechthoek voor het.

Bij wijze van experiment vertelde ik een mop.

We lachten dat het goed was en bedachten voor het gemak
de nacht waarin we elkaar grondig hebben ontdekt.

Om alles nog mooier te maken vlogen er fluitende vogels uit je ogen
stak ik de zon aan om de stralen je gezicht te doen aaien.
Samen ontwaken verklaarden we heilig.
Voor het eerst iets in koor, namelijk zalig, gezegd.

Na nog wat te hebben geschapen als woorden die eindigden op -w
het geluk van de één die per ongeluk de lievelingsdrank
van de ander koopt en een gedeelde muzieksmaak

zei je plotseling: 'Hey, wat nu als dit allemaal uitlekt?’

Je bedoelde natuurlijk dat Goden niet met elkaar slapen
maar je bracht me op een lumineus idee.

Ik gooide een balletje op en noemde het aarde.
Daarop bouwde ik zo vlug als ik kon een stad van huizen.

Ik schafte alle blikken mens aan die ik vinden kon en maakte hen
één en al oor. Ik klom op twee daken en schreeuwde ons verhaal
ervanaf. Bijna alle mensen hadden niks door. God is liefde, spraken ze.

Helaas had één wijsneus me in de gaten. Hij diende bezwaar in
bij de raad van realisme. Daar trok men massaal ons bestaan in twijfel.
Bewijzen tegen ons kwamen in de grootsten getale.
Dat voor ons was pietluttig en pover.

Game over.