Biomolecular machines

[Teleological]

Sorry for posting so many Off topic posts in here

I am at work now and will start really reading your thread when I get home.

Cool.

 

[nauseous_monkey]

Here's the crux of the matter, anyone wishing to discuss these issues in the depth demanded by posts #1 & 3 would choose a forum populated by experts in these fields, and not a branch of an IT forum's "Offtopic".

Anyone wishing to discuss these matters in general/principle would have summarised them to a couple of paragraphs not requiring multiply posts.

and

How can you judge Teo if you are not a research scientist? (you admitted that yourself)

I found it weird that even Devill admitted that it is impossible to really contribute anything to this thread if you are not 'research scientist'.... and then reading alloytoo's post you soon realize that this thread has nothing to do with contributing anything. Teleo is here to push his fat juicy mind turd and that's it!

Devill wants us to 'leave teleo alone' but we simply cannot. Teleo repetitively posts plagiarized articles from elsewhere on the interweb, and then wants people to say 'Wow... yes it is very complex teleo.... that must mean it was designed right!" and if you do not say that he claims that you are going off topic or trolling etc etc.

No one knows what the hell teleo is on about. I that have studied alot of biochemistry thinks that his posts are pointless and leaning towards just plain rediculous. It is not the fancy wording you see... it is the 'lost in translation' aspect. He can spew as much jargon at you as you want.... but the fact remains... he is preaching Intelligent Design.

Now if he wants to do that then he should goto PD... we will take him on there.... but here we talk science buddy.


And no Devill... this is not about POV's this is about truth versus Lies. Teleo is a liar. We are simply pointing it out. A cunning two-bit liar which hides behind 'copy-paste' jobbies.

ah well. Nuf Sed.

 

[antowan]

/me pops in to see what is happening here.

 

[w1z4rd]

Yet you refuse to allow Teo to post his own thinking? And yes he does not just Copy and paste, you just refuse to actually debate the statements with him like adults.

You are a hypocrite.

And you are lying. How the fluck am I refusing him posting his own thinking? If its science, its good and open for review, if it looks like pseudoscience, we will be critical but open for review. Thats what scientists do. ffs man, get a clue.

Why can he not have his opinion and you yours?

Sorry.. I have noticed he posted a lot here. You must be completely blind.. or lying.. again.

Lol, you are pathetic, you admit to posting things that are incorrect YET you will not give Teo the chance to post and learn. You do not give him any room..... Go look at NM's post, no relevance to the thread, its just for insulting Teo....and you guys just fan the flames.

Dude.. you are seriously the most dishonest person I have met in a long time on myadsl. Could you point out where I "disagreed" with him? I was merely commenting on his use of mechanical analogies which seriously looked like he was hinting strongly at design. Of course, you dont understand what the heck we are talking about..

How can you judge Teo if you are not a research scientist? (you admitted that yourself)

Im not judging him.. I am commenting on his comment. Stop lying.

W1z4rd? You tell Teo he is wrong, yet you have not presented any form of qualification in biology/physiology.

I said he was wrong?? REALLY? Show me where I said he was wrong.

Once again.. for the learning impaired. My comments where about his use of analogies, and if we are going to start talking design.. its no longer science and should be moved to the pseudoscience section.

All I am saying is get of your high horsies and play nice because you are being really retarded at the moment.

Get an education. Learn to read.

People like you annoy me. You got EVERY point wrong. Why the heck should I bother responding to you if you make up lies, twist the truth, and act like a 24/7 troll? lame lame lame lame.

NOW DEVILL.. tell me. What is teo`s point.. what is mine? Now that I have said it several times?

Antowan.. you might as delete all posts by Devill.. and all posts by me after Devill posted.

 

[alloytoo]

NOW DEVILL.. tell me. What is teo`s point.. what is mine? Now that I have said it several times?

Antowan.. you might as delete all posts by Devill.. and all posts by me after Devill posted.

Teo apparently doesn't have a point. This thread is merely a "scrapbook" to post interesting links, and his highlighting of certain words doesn't imply any promotion of design, it's merely for the spelling bee.

Soon he may well post a list of all your spelling mistakes by way of an exercise. Folks like you and I are too important to correct our own spelling mistakes, that's what we have editors for.

 

[Devill]

Point Taken.

Enjoy the 'Ctrl + C' and 'Ctrl + V'

I win that round, then ey

Wow.. you really stick on human analogies teo. An analogy is not evidence for anything.

Just not in the science section please.. keep psuedoscience to the PD section

Tell me how these are not just your opinions?

Also please point out the relevance of these posts.

And you are lying. How the fluck am I refusing him posting his own thinking? If its science, its good and open for review, if it looks like pseudoscience, we will be critical but open for review. Thats what scientists do. ffs man, get a clue.

See there you go again, I have no problem in you challenging his ideas facts ect ect but please be more civil about it and drop the god complex.

Sorry.. I have noticed he posted a lot here. You must be completely blind.. or lying.. again.



Dude.. you are seriously the most dishonest person I have met in a long time on myadsl. Could you point out where I "disagreed" with him? I was merely commenting on his use of mechanical analogies which seriously looked like he was hinting strongly at design. Of course, you dont understand what the heck we are talking about..



Im not judging him.. I am commenting on his comment. Stop lying.


I said he was wrong?? REALLY? Show me where I said he was wrong.

Once again.. for the learning impaired. My comments where about his use of analogies, and if we are going to start talking design.. its no longer science and should be moved to the pseudoscience section.

This is his thread and if he can give some facts and then make some Observations you have a right to challenge them but again get of your high horse and be more civil.
You don't know everything yet you post like you do......


People like you annoy me. You got EVERY point wrong. Why the heck should I bother responding to you if you make up lies, twist the truth, and act like a 24/7 troll? lame lame lame lame.

Your opinion. Again because its your opinion does not make it right / the truth.
NOW DEVILL.. tell me. What is teo`s point.. what is mine? Now that I have said it several times?

ROFL this proved that you did not even read the previous post where even alloytoo stated that this was a "scrap book" and he wont read it but Teo is free to continue IHO.

Antowan.. you might as delete all posts by Devill.. and all posts by me after Devill posted.

Now please for the last time I am telling you that I do not ahve a problem if you actually read the other posts and also show some respect but thus far you have been thinking that you are the final authority on everything.

You are a bigot and a hypocrit. Please also I would still like to see the papers you have written... where were they published and all that.

 

[nauseous_monkey]

Devill. You have never contributed to any thread in a meaning full way. Show me once that you debated a good point without getting emotional.

 

[Devill]

Devill. You have never contributed to any thread in a meaning full way. Show me once that you debated a good point without getting emotional.

LOL

Coming from you? Lol, you NEVER have anything to say except to inflame situations. I told you last time the only way you get any attention is by trolling, then I even sent you a friend invite so you would not be so lonely.... ag shame.

You have already been banned once, don't make it a second time.

Ps. Science section, no debating here just facts....isn't that what you always say?

Ok as for your question, we can start here. If you want I can pm you the rest because we have completely screwed up this thread.
http://mybroadband.co.za/vb/showpost.php?p=1791592&postcount=18

 

[nauseous_monkey]

LOL

Coming from you? Lol, you NEVER have anything to say except to inflame situations. I told you last time the only way you get any attention is by trolling, then I even sent you a friend invite so you would not be so lonely.... ag shame.

You have already been banned once, don't make it a second time.

Ps. Science section, no debating here just facts....isn't that what you always say?

Ok as for your question, we can start here. If you want I can pm you the rest because we have completely screwed up this thread.
http://mybroadband.co.za/vb/showpost.php?p=1791592&postcount=18

Wow, one post where you contributed to the discussion constructively. You are on a winning streak ey! At his rate you'll own all of us.

Devill, you will never change. You are transparently ignorant. Blinded by God. as soon as you realize that you are deluded, maybe you'll be a better forumite.

 

[Devill]

Wow, one post where you contributed to the discussion constructively. You are on a winning streak ey! At his rate you'll own all of us.

Devill, you will never change. You are transparently ignorant. Blinded by God. as soon as you realize that you are deluded, maybe you'll be a better forumite.

ROFL so if you believe in a god then you are a bad formite?

See why you are a joke?

You strugle with the basics of debating, well that and stringing a proper sentence together.

How did God enter this discussion?

I really thing you should learn to read, see the part where I said I will pm you the rest if you really want to see it?

Again you are nothing but a jester good for a laugh and nothing more.

 

[nauseous_monkey]

ROFL so if you believe in a god then you are a bad formite?

See why you are a joke?

You strugle with the basics of debating, well that and stringing a proper sentence together.

How did God enter this discussion?

I really thing you should learn to read, see the part where I said I will pm you the rest if you really want to see it?

Again you are nothing but a jester good for a laugh and nothing more.

It is pretty clear to everyone here that your blind support of ID threads is characteristic of your god delusion. You believe in God and thus you think anything that sounds like it might support that idea you blindly support.

Why else would a rational thinking person support any of the crazy crap teleo posts?

 

[Devill]

It is pretty clear to everyone here that your blind support of ID threads is characteristic of your god delusion. You believe in God and thus you think anything that sounds like it might support that idea you blindly support.

Why else would a rational thinking person support any of the crazy crap teleo posts?

LOL

See you talk so much out of your ass, where have I supported Teo?

I stated that Alloytoo and W1z4rd were acting like Idiots not that they were wrong...

Please learn to read

I have told you before that you are a blind zealot for hating religion....

Lol, you are worse than this idea that you hate...

Shame you should rather go study. You are a troll, just go and look at the first post in this thread by you....

Maybe oneday when you have stopped blaming religion for everything thats wrong in your life and own up you will grow up.

Till then stop trolling.

 

[nauseous_monkey]

I'm officially bored by you.

 

[Devill]

I'm officially bored by you.

K thx bye

Don't let the door slam you on your ass on the way out

 

[w1z4rd]

Devill, I tried to reason with you. You are a waste of time to me. Bye. Ignore list +1.

 

[nauseous_monkey]

I have also officially added him to my ignore list.

 

[Teleological]

Seriously guys, if you want to participate in the thread, make it relevant.
Here:

The anaphase promoting complex/cyclosome: a machine designed to destroy.

The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase that has essential functions in and outside the eukaryotic cell cycle. It is the most complex molecular machine that is known to catalyse ubiquitylation reactions, and it contains more than a dozen subunits that assemble into a large 1.5-MDa complex. Recent discoveries have revealed an unexpected multitude of mechanisms that control APC/C activity, and have provided a first insight into how this unusual ubiquitin ligase recognizes its substrates.

What a provocative sounding title for an article to be published in Nature reviews. Molecular cell biology. Some might think the author published it to push his fat juicy mind turd . All those design lingo-mumbo-jumbo, preaching Intelligent Design, so it must be designed right? Just another two-bit creationist that spins around jargon. Right? Mmmm.

So let's see what the article says and what does the complex actually do?

First of all, it is an E3 ubiquitin ligase that forms part of the protein quality control system that plays a crucial role in protein homeostasis. The complex tags damaged, misfolded and other proteins ready to be degraded with ubiquitin. Once proteins are tagged by ubiquitin, the are transferred and degraded by the 26S proteasome machinery (see below). Activity of the complex is strictly regulated and is dependent on one of several co-activator proteins. These co-activator proteins are in turn also strictly controlled during various phases of the cell cycle.

Basically what it does is selectively recognizes and tags proteins for destruction at the correct time during key events of mitosis (cell division). Two major functions include:
Cyclin proteolysis to activate initiation of anaphase (Cyclin B in particular)
Initiates sister-chromatid separation through the selective degradation of securin.

Inactivation of this complex results in death in all species in which it has been investigated so far.

That is it, that is all it does. It does not prove anything.



Now if you think the above sounding title was provocative, here is another one:
The 26S proteasome: a molecular machine designed for controlled proteolysis.

In eukaryotic cells, most proteins in the cytosol and nucleus are degraded via the ubiquitin-proteasome pathway. The 26S proteasome is a 2.5-MDa molecular machine built from approximately 31 different subunits, which catalyzes protein degradation. It contains a barrel-shaped proteolytic core complex (the 20S proteasome), capped at one or both ends by 19S regulatory complexes, which recognize ubiquitinated proteins. The regulatory complexes are also implicated in unfolding and translocation of ubiquitinated targets into the interior of the 20S complex, where they are degraded to oligopeptides. Structure, assembly and enzymatic mechanism of the 20S complex have been elucidated, but the functional organization of the 19S complex is less well understood. Most subunits of the 19S complex have been identified, however, specific functions have been assigned to only a few. A low-resolution structure of the 26S proteasome has been obtained by electron microscopy, but the precise arrangement of subunits in the 19S complex is unclear.

Published in Annual review of biochemistry.

Here is a very nice video describing the process!


Does this prove Intelligent Design? No! These articles just explain how these macromolecular structures work. That is it! Nothing more!

 

[Teleological]

More great videos. This time about RNAi.
RNAi Discovered
RNAi is cool (same one with explanation)

 

[Teleological]

Cell's 'Quality Control' Mechanism Discovered

Researchers in Japan and Canada have discovered a key component of the quality control mechanism that operates inside human cells – sometimes too well. The breakthrough has significant implications for the development of new treatments for cystic fibrosis (CF) and some other hereditary diseases, the researchers say.

Their results were published July 25 in the journal Science.

Dr. Kazahiro Nagata and colleagues at Kyoto University and the Japan Science Technology Agency, and Dr. David Thomas and Dr. Gregor Jansen at McGill University in Montreal, have discovered the important role played by an enzyme called ERdj5 inside the cell's endoplasmic reticulum (ER).

The ER acts as a sort of packaging plant that folds and prepares proteins for distribution inside or outside the cell. But when proteins are misfolded in the ER, they must be destroyed in a degradation process – and that is where ERdj5 comes into play.

"ERdj5 is like a quality control inspector," explained Dr. Thomas, McGill's Chair of Biochemistry and Canada Research Chair in Molecular Genetics. "If you ever owned an AMC Pacer and you now drive a BMW, you know the difference quality control can make. That's what ERdj5 does, it recognizes when a protein has 'manufacturing defects' and degrades it before it can be distributed."

The ERdj5 enzyme is the first protein found to be capable of breaking the disulfide bonds that hold the misfolded proteins together in the ER. Once those bonds are broken, the researchers say ERdj5 also helps other enzymes and molecules break down the misfolded proteins completely so that the constituent amino acids can be recycled for further protein synthesis.

"Unfortunately, the mechanism sometimes works a little too well," Dr. Thomas said. "It insists on BMW quality when a Honda would do. For example, some people carry a mutated version of the protein CFTR. The mutated protein is damaged but would still work fine if it were distributed, but in some individuals, the quality control mechanism insists on degrading it. It's the degradation of the protein, not the mutation itself, which causes cystic fibrosis. We're hoping this discovery will open up new avenues of research into treatments for CF."

Cells' very own natural selection mechanism to remove mutated proteins from the population .

This mechanism is not limited to eukaryotic cells. The ERdj5 enzyme operates in eukaryotes. The DnaJ enzyme is a homlogous chaperone protein in bacteria that carries out virtually the same function. Also known as heat shock 40 proteins (HSP40).
The DNAJ gene family.
DnaJ is also found in primitive eubacteria, indicating that the system was present VERY early on during evolution.
Eubacteria:

Most eubacteria are gram positive, and they are generally less structurally complex than other bacteria.

Articles:
ERdj4 and ERdj5 Are Required for Endoplasmic Reticulum-associated Protein Degradation of Misfolded Surfactant Protein C
ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ER.

 

[Teleological]

Cell division​

The cell cycle is a highly regulated process with various positive- and negative-feedback systems to ensure that cells divide in a controlled manner. The process consists of a sequence of events by which a growing cell duplicates all its components and divides into two daughter cells, each with sufficient machinery to repeat the process. In eukaryotic cells, one round of cell division consists of two “gap” phases termed G1- and G2-, an S-phase during which duplication of all DNA happen, and an M-phase where proper segregation of duplicated chromosomes and chromatid separation occur. During each of these phases, regulatory signaling pathways monitor the successful completion of events in each phase before proceeding to the next phase.

Two recent articles from sciencedaily:

Being A Control Freak Aids Dividing Cells

Micromanagers may generate resentment in an office setting, but they get results in your body. New data indicate that a dividing cell takes micromanagement to the extreme, tagging more than 14,000 different sites on its proteins with phosphate, a molecule that typically serves as a signal for a variety of biological processes.

This preponderance of signals suggests that the cell may become a control freak during the division process, regulating each of its parts, no matter how obscure. It may take extreme measures to ensure that each "daughter" receives a full complement of cellular material. The new data—published online the week of July 28 in PNAS—open unexplored frontiers to developmental biologists, cancer researchers, and others who study cell growth and proliferation.

"There's a massive wave of phosphorylation in dividing cells, much bigger than anyone expected," says HMS associate professor of cell biology Steven Gygi, who is corresponding author on the study. "This discovery implies that we've severely underestimated the scope of regulation in cell division for decades, which has implications for our understanding of a wide-range of diseases and developmental defects linked to the cell cycle, from cancer to holes in the heart."

Traditionally, researchers probed cell division by zooming in on a particular gene or protein and tracing its interactions. But Gygi took a different approach. A leader in the emerging field of "proteomics," which involves looking at thousands of proteins at once, his team used an instrument called a mass spectrometer to essentially take a wide-angle shot of dividing cells, capturing information that narrow studies missed. The panoramic view revealed a surprising level of signaling activity throughout the cell.

"An enormous number of proteins—more than 1,000—became highly phosphorylated during cell division, some more than 10 times," says postdoctoral researcher Noah Dephoure, who ran the experiment.

In collaboration with Chunshui Zhou, a researcher in HMS professor of genetics Stephen Elledge's lab, Dephoure worked with human cells, dividing them into two dishes. (The cells used are HeLa cells, which, while derived from a tumor, are used for many experiments because they thrive in culture. It's possible that some of the signaling events reported here are unique to these cells.) The first dish received nutrients with "heavy" carbon atoms—more massive than their "light" counterparts, which are abundant in nature. The second dish received normal nutrients, plus a toxic chemical to freeze the cells mid-division.

Dephoure and Zhou mixed all the cells together, killed them, chopped their constituent proteins—which were preserved—into small pieces called peptides, and fed these into a mass spectrometer. The instrument distinguished between otherwise identical peptides, based on the presence of "heavy" or "light" atoms, generating a ratio for each peptide. Dephoure paid particular attention to the ratios for peptides containing phosphate groups and uncovered major differences between the two populations of cells.

The dividing cells harbored a staggering number of regulated phosphate groups in unexpected places.

Gygi hypothesizes that the cell uses phosphorylation to break down every last protein complex before dividing. "Maybe the cell does something akin to putting Humpty Dumpty back together again at the end," he says.

"The massive number of phosphorylation changes in cell division strongly suggests that it involves a massive reorganization of the cell," adds HMS Department of Systems Biology chair Marc Kirschner, who was not involved in the study.

"Or the cell might phosphorylate everything to ensure that it hits a few key targets critical for proper division," says Dephoure. Under this scenario, extraneous phosphorylation may cloud the picture.

Armed with the team's list of proteins and phosphorylation sites, labs can conduct additional experiments to resolve this debate. They can investigate particular phosphorylation events and determine which ones contribute to successful regulation of cell division. Some may present therapeutic targets for patients with cell cycle diseases such as cancer.
"

Article 2:
Positive-feedback System Ensures That Cells Divide

In the life of every cell, there’s a point of no return. Once it enters the cell cycle and passes a checkpoint known as “Start,” a cell will follow the steps it needs to divide — no matter what changes might occur in its environment.

Now scientists at Rockefeller University show that a positive-feedback system ensures that a cell that has made the decision to divide finishes what it has started.

Part of the decision process includes activating more than 200 genes simultaneously, a formidable problem considering the noisy environment of the cell. “Given how difficult it is for a cell to activate just one gene, activating 200 at the same time seems like a very difficult task,” says Jan Skotheim, a postdoc who collaborated on the research with Frederick Cross, head of the Laboratory of Yeast Molecular Genetics, and Eric Siggia, head of the Laboratory of Theoretical Condensed Matter Physics. “And the way the cell solves this challenge is through positive feedback. It keeps all these events in sync.”

Positive-feedback mechanisms allow cells to adapt to changes in their environment rapidly and efficiently. In the case of cell division, the key is a pair of molecules called Cln1 and Cln2, part of a family of proteins known as G1 cyclins. Skotheim and his colleagues, including graduate student Stefano DiTalia, show that when budding yeast (Saccharomyces cerevisiae) cells sense that they are big enough to divide, they synthesize an activator molecule that triggers a positive feedback system in which Cln1 and Cln2 advance their own expression.

“So what happens is that the very rapid ramp-up of the G1 cyclins during Start lead to all those target genes getting fired synchronously,” says Skotheim. “It’s a function of positive feedback that hasn’t been thought of before: synchrony and coherence.”

For the genes to be fired synchronously, a protein called Whi5 must be exported from the nucleus, and kept out until the two daughter cells are born. During Start, which lasts approximately three minutes, Cln1, Cln2 and the activator molecule all collaborate to kick out Whi5. Once out, Cln1 and Cln2 must continue to advance their own expression in order to keep Whi5 out. Then, the moment the two daughter cells separate, the G1 cyclins are inactivated, Whi5 enters back into the nucleus and the complex detaches. In previous work, the team showed that the export of Whi5 is the molecular event that signals Start. Now they show that a positive-feedback mechanism is what drives it.

In the past, when scientists tested the possibility that positive feedback could be behind cell division, the results always came out negative. But Skotheim took a different approach from that of his predecessors. Instead of averaging the results across many cells, he looked at data from individual cells, an approach that minimizes data loss.

Working with two strains of single-celled budding yeast, only one of which had Cln1 and Cln2, the researchers observed that most cells without the two molecules had less predictable divisions. They took longer to start dividing, and when they finally passed Start, the time it took them to complete the process varied considerably. Some cells, in fact, didn’t bud at all.
”

There is a considerable amount of cross-talk between DNA repair mechanisms, cell cycle signaling pathways, programmed cell death pathways (autophagy, apoptosis, mitotic catastrophe etc.) and other cell stress signaling pathways. All these intricately interwoven pathways serve to ensure accurate cell division and removal of faulty cells from a population through programmed cell death. The problem comes when one of the checkpoints or programmed cell death pathways become corrupted and causes uncontrolled cell division in multicellular organisms. Cancer is one of the outcomes of abrogated cell death signaling and uncontrolled cell division.

Bacterial cell division is also a well orchestrated process and programmed cell death is not limited to multicellular organisms as bacteria also contain the necessary pathways to self destruct.
E.g.:
Engelberg-Kulka H, Amitai S, Kolodkin-Gal I, Hazan R. Bacterial programmed cell death and multicellular behavior in bacteria. PLoS Genet. 2006 Oct;2(10):e135.

Cool huh ?