RNA measurements may yield less insight than assumed

High-throughput characterization of protein–RNA interactions doi: 10.1093/bfgp/elu047 RNA-binding proteins (RBPs) are important regulators of eukaryotic gene expression. Genomes typically encode dozens to hundreds of proteins containing RNA-binding domains, which collectively recognize diverse RNA sequences and structures. Recent advances in high-throughput methods for assaying the targets of RBPs in vitro and in vivo allow large-scale derivation of RNA-binding motifs as well as determination of RNA–protein interactions in living cells. In parallel, many computational methods have been developed to analyze and interpret these data. The interplay between RNA secondary structure and RBP binding has also been a growing theme. Integrating RNA–protein interaction data with observations of post-transcriptional regulation will enhance our understanding of the roles of these important proteins. http://bfg.oxfordjournals.org/content/early/2014/12/13/bfgp.elu047.short?rss=1

Dionisio

gpuccio Merry Christmas! Thank you for the encouraging words. I appreciate them very much, specially coming from you, who could teach a few things to many of us here! :) Dionisio

Connecting the Cytoskeleton to the Endoplasmic Reticulum and Golgi DOI: http://dx.doi.org/10.1016/j.cub.2014.05.033 A tendency in cell biology is to divide and conquer. For example, decades of painstaking work have led to an understanding of endoplasmic reticulum (ER) and Golgi structure, dynamics, and transport. In parallel, cytoskeletal researchers have revealed a fantastic diversity of structure and cellular function in both actin and microtubules. Increasingly, these areas overlap, necessitating an understanding of both organelle and cytoskeletal biology. This review addresses connections between the actin/microtubule cytoskeletons and organelles in animal cells, focusing on three key areas: ER structure and function; ER-to-Golgi transport; and Golgi structure and function. Making these connections has been challenging for several reasons: the small sizes and dynamic characteristics of some components; the fact that organelle-specific cytoskeletal elements can easily be obscured by more abundant cytoskeletal structures; and the difficulties in imaging membranes and cytoskeleton simultaneously, especially at the ultrastructural level. One major concept is that the cytoskeleton is frequently used to generate force for membrane movement, with two potential consequences: translocation of the organelle, or deformation of the organelle membrane. While initially discussing issues common to metazoan cells in general, we subsequently highlight specific features of neurons, since these highly polarized cells present unique challenges for organellar distribution and dynamics. http://www.cell.com/current-biology/abstract/S0960-9822(14)00598-3 Dionisio

Dionisio: Merry Christmas to you! :) (And please, go on with your very good work). gpuccio

Axonal Transport: Cargo-Specific Mechanisms of Motility and Regulation DOI: http://dx.doi.org/10.1016/j.neuron.2014.10.019 Axonal transport is essential for neuronal function, and many neurodevelopmental and neurodegenerative diseases result from mutations in the axonal transport machinery. Anterograde transport supplies distal axons with newly synthesized proteins and lipids, including synaptic components required to maintain presynaptic activity. Retrograde transport is required to maintain homeostasis by removing aging proteins and organelles from the distal axon for degradation and recycling of components. Retrograde axonal transport also plays a major role in neurotrophic and injury response signaling. http://www.cell.com/neuron/abstract/S0896-6273(14)00917-9 Dionisio

AVS Thank you for your nice comments. :) Merry Christmas! Dionisio

hrun0815 Thank you for your nice comments. :) Merry Christmas! Dionisio

wd400 Thank you for your nice comments. :) Merry Christmas! Dionisio

I don't think anyone was the least bit upset but the contents of your posts Dionisio. The sheer volume of them is kind of annoyingly spammy. And when you combine all the links with your refusal to discuss any topic in any detail you end up looking a bit a squid -- retreating rapidly while sending forth a (l)ink cloud to try cover your lack of any argument. So, no "discomfort", just mild;y amused bewilderment about what you think you are achieving. wd400

AVS:

So Joe, I take it you are unable to find a scientific source that only claims ATP synthase evolved and does not provide evidence for this claim?

That isn't my claim. Obviously you have other issues.

Also, it’s not that evolution can’t be modeled, the problem is it is too complex a process for us to successfully model right now.

Again your equivocation is duly noted. Evolution can be modeled. Unguided evolution producing something of note cannot be. As I said you think your ignorance means something but it doesn't. Joe

Wow, Dionisio. That's some mighty delusion. Can you point to any place where the content of your C/P jobs was actually discussed? That's like claiming that BA77's posts stimulate discussion. hrun0815

News, As you can see, this thread got reactivated after I posted a few related references to recent research reports, which apparently caused some itching and discomfort to some commenters here. :) Let's ignore the whiners, specially when they're barking up the wrong trees. Let's keep moving on. :) Marry Christmas! Dionisio

Endosomal transport of septin mRNA and protein indicates local translation on endosomes and is required for correct septin filamentation DOI 10.1002/embr.201338037 Endosomes transport lipids and proteins over long distances by shuttling along microtubules. They also carry mRNAs on their surface, but the precise molecular function of this trafficking process is unknown. http://embor.embopress.org/content/15/1/94

the precise molecular function of this trafficking process is unknown What else is new? Many things are still unknown. Which means that more research is required. More resources have to be invested in that research. As new discoveries are made, more light is shed on the biological big picture, unveiling elaborate cellular and molecular processes, amazingly orchestrated choreographies, that demand further explanation. This is simply fascinating. That's why we look forward, with much anticipation, to reading newer reports coming out of research labs. Rejoice! :) Dionisio

#163 addendum

DOI: 10.1126/science.1256898 The eukaryotic cell contains membrane-bound organelles with distinct functionality and composition. Preservation of organelle identity depends on the highly selective transfer of proteins and lipids between compartments. Central to this are transport carriers called vesicles. Mechanisms are required not only for the selective incorporation of specific cargos into vesicles as they bud off a donor organelle, but also for the correct delivery to an acceptor organelle. SNARE proteins on the vesicle and destination organelle drive membrane fusion after arrival and have been implicated in contributing to specificity in choice of organelle. However, upstream of the fusion step, a process called tethering is thought to initially attach the vesicle to the destination organelle and then bring it close to allow the SNARE proteins on opposite membranes to interact. The importance of tethering in conferring specificity to membrane traffic is currently unclear. http://www.sciencemag.org/content/346/6209/1256898.abstract

Dionisio

All you need to know is described in sufficient details at the very beginning. Just look carefully, so you can see it. If you miss it, then it’ll be described again, even more clear, at the very end. But don’t wait till then. Try to get it now. :)

Ah, yes, Dionisio. You are just a student who just posts interesting material for others. But you refuse to tell anybody what specifically is interesting. Or my assessment of you is actually accurate: you 'literature bluff' yourself through these threads and scared witless of being nailed down on any specific statement lest you be wrong and your ignorance is exposed. hrun0815

‘How do molecules in the cell find their proper destinations’, is a profound question in my book.

I think many biologists agree with you. A countless amount of work has been done on that specific question for a long time. So much so that Günter Blobel was awarded the Nobel prize "for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell" 15 years ago. (Cue two standard ID retorts: 1) you didn't provide enough details! 2) How did it get there in the first place?) hrun0815

Well I at least thought you’d take a guess Dio, but I guess not. Those proteins are coat proteins and it’s interesting that you couldn’t name them because 4 posts after linking that video, you linked us to another site that defined those same coat proteins and put a virtually identical picture right at the top of the page. So the question is, do you actually read the stuff you post? Sorry Dio, you failed your first exam. “That's why we look forward, with much anticipation, to reading the next reports coming out of research labs.” Maybe you really do read them, but does Dio actually learn anything from them? Certainly doesn’t seem like it. The autodidactic school system seems to be failing you Dio, you must have a bad teacher. AVS

The specificity of vesicle traffic to the Golgi is encoded in the golgin coiled-coil proteins DOI: 10.1126/science.1256898 http://www.sciencemag.org/content/346/6209/1256898.abstract Dionisio

Intracellular express -- why transport protein molecules have brakes Check out all these videos: http://article.wn.com/view/2010/05/21/Intracellular_express_why_transport_protein_molecules_have_b/ Dionisio

A Day in the Life of a Motor Protein https://www.youtube.com/embed/tMKlPDBRJ1E Dionisio

I take it you don't know what those proteins are Dio? AVS

Cellular Uptake Mechanisms and Endosomal Trafficking of Supercharged Proteins DOI: http://dx.doi.org/10.1016/j.chembiol.2012.06.014 Supercharged proteins (SCPs) can deliver functional macromolecules into the cytoplasm of mammalian cells more potently than unstructured cationic peptides. Thus far, neither the structural features of SCPs that determine their delivery effectiveness nor their intracellular fate postendocytosis, has been studied. http://www.cell.com/chemistry-biology/abstract/S1074-5521(12)00222-0 Dionisio

BmCREC Is an Endoplasmic Reticulum (ER) Resident Protein and Required for ER/Golgi Morphology http://www.jbc.org/content/288/37/26649.abstract Dionisio

Apoptosis-linked Gene-2 (ALG-2)/Sec31 Interactions Regulate Endoplasmic Reticulum (ER)-to-Golgi Transport A POTENTIAL EFFECTOR PATHWAY FOR LUMINAL CALCIUM* doi: 10.1074/jbc.M114.561829 Luminal calcium released from secretory organelles has been suggested to play a regulatory role in vesicle transport at several steps in the secretory pathway; however, its functional roles and effector pathways have not been elucidated. http://www.jbc.org/content/289/34/23609.abstract Dionisio

I will believe you Dio, don't worry. So what is it? AVS

At the very beginning and end of what? I take it you don’t know what they are?

Can't tell you what it is, you won't believe me. You gotta find it yourself. Look carefully, you'll see it. It's amazing. Can't miss it. :) Dionisio

Cofilin recruits F-actin to SPCA1 and promotes Ca2+-mediated secretory cargo sorting doi: 10.1083/jcb.201311052 http://jcb.rupress.org/content/206/5/635.abstract Dionisio

Cab45 is required for Ca2+-dependent secretory cargo sorting at the trans-Golgi network doi: 10.1083/jcb.201207180 http://jcb.rupress.org/content/199/7/1057.abstract Dionisio

At the very beginning and end of what? I take it you don't know what they are? AVS

Hey Dio, at about the 1:45 mark of that new protein packing video I can’t tell what those greenish things are, did you come across it by any chance?

All you need to know is described in sufficient details at the very beginning. Just look carefully, so you can see it. If you miss it, then it'll be described again, even more clear, at the very end. But don't wait till then. Try to get it now. :) Dionisio

Secretory proteins hail a cab at the TGN doi: 10.1083/jcb.1997iti2 After moving through the secretory pathway from the ER to the Golgi apparatus, proteins are sorted at the TGN for delivery to their final destinations. How soluble proteins are selected for secretion outside of the cell is unclear,... http://jcb.rupress.org/content/199/7/1018.2.full Dionisio

Hey Dio, at about the 1:45 mark of that new protein packing video I can't tell what those greenish things are, did you come across it by any chance? AVS

Ok, let's not get confused so easily. Some PCB may look messy, but they handle a lot of data processing very elegantly. One of the beauties of the biological systems is that it does much more than all the most sophisticated systems humans have created, but still scientists can't figure out exactly how all that is done in details. Tremendous technological advances lately have allowed researchers to discover more details, but some old questions remain and many new ones have popped up. Much more is known today than a few years ago, but we ain't there yet. We are witnessing a system that seems designed and setup to handle even stochastic scenarios. We ain't seen nothing yet. That's why we look forward, with much anticipation, to reading the next reports coming out of research labs. This is indeed fascinating. Let's enjoy it! Dionisio

Coordinated protein sorting, targeting and distribution in polarized cells doi:10.1038/nrm2525 http://www.nature.com/nrm/journal/v9/n11/full/nrm2525.html Dionisio

Wow, remember when I caught all that flak from you guys for saying the molecular environment of the cell is in reality a mess? Here's some quotes from what was said about the simulation in a post above: "Alain Viel, the director of undergraduate research at Harvard and a member of the BioVisions team, likened the inside of a cell to a rush-hour subway platform. “If there’s a big crowd in front of you, there’s a good chance you might not even see the train,” he said." "kinesin doesn’t look like a molecule out for a stroll. Its movements are barely constrained randomness." "In reality, however, the parts of our cells don’t operate with the precise movements of the springs and gears of a clock. They flail blindly in the crowd. Our cells work almost in spite of themselves." Interesting! Thanks Dio! AVS

Hydrophobic handoff for direct delivery of peroxisome tail-anchored proteins doi:10.1038/ncomms6790 http://www.nature.com/ncomms/2014/141217/ncomms6790/full/ncomms6790.html Dionisio

Tracking Protein Function in Living Cells https://www.asme.org/engineering-topics/articles/bioengineering/tracking-protein-function-living-cells Dionisio

The Inside Story of Cell Communication http://learn.genetics.utah.edu/content/cells/insidestory/ Dionisio

Directing Traffic: How Vesicles Transport Cargo http://learn.genetics.utah.edu/content/cells/vesicles/ Dionisio

The Get1/2 transmembrane complex is an endoplasmic-reticulum membrane protein insertase doi:10.1038/nature13471 http://www.nature.com/nature/journal/v512/n7515/full/nature13471.html Dionisio

SIMIBI twins in protein targeting and localization doi:10.1038/nsmb.2605 http://www.nature.com/nsmb/journal/v20/n7/full/nsmb.2605.html Dionisio

The mechanism of membrane-associated steps in tail-anchored protein insertion doi:10.1038/nature10362 Tail-anchored (TA) membrane proteins destined for the endoplasmic reticulum are chaperoned by cytosolic targeting factors that deliver them to a membrane receptor for insertion. Although a basic framework for TA protein recognition is now emerging, the decisive targeting and membrane insertion steps are not understood. http://www.nature.com/nature/journal/v477/n7362/full/nature10362.html Dionisio

Watch Proteins Do the Jitterbug http://www.nytimes.com/2014/04/10/science/watch-proteins-do-the-jitterbug.html?_r=0 Dionisio

Three-part handoff delivers proteins to membrane surface http://www.uchospitals.edu/news/2011/20110824-proteins.html Dionisio

Golgin proteins specify destination of vesicle traffic http://www2.mrc-lmb.cam.ac.uk/golgin-proteins-specify-destination-vesicle-traffic/ Dionisio

There is no "proper destination" in the cell. Just random bumping of molecules into other molecules. Stuff happens. Mung

It's ok, biology isn't for everyone. UD is a perfect example of that. AVS

That must be it AVS. :) Box

That would be because you haven't taken a basic biology course boxy. AVS

'How do molecules in the cell find their proper destinations', is a profound question in my book. Box

That still seems like asking how to PCR primers find their targets to me. wd400

WD400 #128, Even if you are correct, the question remains how thousands of DNA fragments are selected on suitability and aligned in the correct sequence. Box

The wrong bits can just as easily been put together. No. The "stitching" process requires homologous sequences which can bind to each other. If the sequences aren't homolgous they oant be put together (absent the chance similarity I discussed above) wd400

I still don’t understand what was wrong about that text you were pointing to

I don't think it's hard to understand. 1) "News" said these results where interesting with regards the "RNA world". In fact, they have nothing to do with any RNA world hypothesis. Indeed it's bizarre someone could think these data could having any bearing on that topic 2) The press release refers to some 'unknown' process regulating the rate at which proteins are produced from mRNA. In fact, many means of regulating that process are known, there doesn't seem to be any reason to invent another unknown one to explain these results (interesting as they may be). I don't think a clearer explanation is possible. wd400

Wd400: The “wrong” bits can’t be put together, unless they happened to share identical streches by chance.

The wrong bits can just as easily been put together. That is the whole point. Drad reconstructs its genome from the fragments of the genome and the fragments of the copies of the genome. From these thousands of fragments it 'chooses' suitable (overlapping) fragments and aligns them in the correct sequence. Any sequence is equally possible but the correct sequence is 'chosen'. Which raises the question: 'How?' Box

You can of course leave it whereever you want, but I'll reiterate my point about PCR. When a molecular biologists sets up a PCR (s)he basically puts some genomic DNA fragments n a tube, adds small DNA molecules homlogous to some part of larger fragments and an enzyme, puts the tube in a heating-machine then walks away. The PCR reaction can only work if those small fragments anneal to the corresponding sections of the target DNA. Nothing in the PCR reaction mediates that binding (apart from the buffers etc that chemically help this process), it's just chemistry. THe process in D. rad. is a good deal more involved that PCR, and there are still "mysteries", in the sense of unsolved parts of the problem. But I don't know why you think there needs to be a top-down process. Moreover, "sequence matters" of course, but it's only the correct (actually ancestral) sequence that can be put back together because the reconstruction is primed from existing sequencees. The "wrong" bits can't be put together, unless they happened to share identical streches by chance. (I don't know, but I bet D. rad. has relatively few "low complexity" regions..) wd400

WD400 #121,

Box: the mystery is how Drad lines them up in the correct sequence

WD400: Why would it need to?

Because, after radiation, there are only isolated fragments of DNA left. And because the sequence matters? Drad restores its genome in the original sequence BTW. After it has repaired its DNA it is as if nothing has happened. Humpty Dumpty has been put back together again. You fail to see why this is mysterious. I fail to see why you don't see the mystery. Let's leave it at that. Box

I still don’t understand what was wrong about that text you were pointing to.

You, the person who supposedly post relevant scientific papers, extracts supposedly salient bits and highlight other parts, you fail to understand what is wrong with the statements? And even after clarification you still don't understand? I would strongly suggest you stop reading papers and start investing in an extremely basic textbook. You have then no chance at all to understand the papers you have been citing.

You seem confused again. Are you referring to my comments addressed to Box? Are you sure you’re not misquoting my comments? Apparently, Box was trying to engage in a serious discussion with some folks in this blog, but things didn’t seem to go quite right, so I expressed my opinion about discussion requirements. I don’t recall saying I was able, capable or willing to engage in serious discussions. Can you show me that text where I said so? If I did, I will correct it. But first, show it to me.

Ah, yes, when you write that "Your interlocutor along with his comrades and fellow travelers don’t seem interested in any serious discussion." and "Their motivations are not clear, but they don’t seem to be serious." you were clearly just talking about Box and his discussion with a single person and not really comparing two groups of people and classifying one as being all for serious discussion and the other not.

Currently, I’m a student (autodidact), hence my opinion here, where so many folks know much more than I do, would not make any difference. Perhaps one thing I can do is to read what others write and ask questions in order to learn more. Also I like to post here some of the materials I’m reviewing lately, in order to share them with other people who might be interested in the given subjects.

Ah, now I get it. You really are interested in becoming the second BA77 of this board. I have to say, you are well on your way. Throw in a couple of bible quotes and youtube videos every now and then and people will not know the difference. Thank you for clarifying this point though. I am certain it is quite useful for others on the board. Cheers. hrun0815

#116 hrun0815

Oh, and re your post 57: it is an iPhone.

FYI - just looked at this in my wife's iPhone and confirmed what you wrote: don't see the post #s if one uses the app for the blog. However, if one looks at the blog directly on the safari browser the post #s do appear. In my Nokia Lumia the post #s show up because I look at the blog directly on the browser, not through an app. The problem with the post #s not showing has to do with the app settings or a bug in that app. Did I get this right? Dionisio

Now, like I stated before, the mystery is how Drad lines them up in the correct sequence Why would it need to? When molecular biologists run a PCR they don't need to have the the primers line up with the target. The specific enzymes that catalyze priming in D. rad. are not entirely known, but I do see why the process needs oversight (any more than PCR does). wd400

WD400 #118, Now this time it's you who misunderstands :) Drad is carrying multiple copies of its genome. 7 kGy of ionizing radiation shatters the genome and the copies - breakage is random (i.e., it doesn't occur on both copies at the same place). Now because there are multiple copies, repair by homologous recombination can occur between the copies. For this repair Drad needs overlapping genomic fragments. There are multiple homologous fragments - fragments stemming from the multiple copies. However Drad needs overlapping fragments (see fig.7). Because there are so many scattered fragments these are likely available. Hundreds of overlapping genomic fragments can be used as respective primers and templates for 3’ end elongations. The correctly sequenced hundreds of overlapping genomic fragments (see fig.7) function as a template for genome repair. Now, like I stated before, the mystery is how Drad lines them up in the correct sequence - 'whence the information?' I had an extensive email exchange with one of the researchers who explicitly confirmed the mystery.

Yes, that's exactly the biggest remaining mystery, how are the homologous fragments brought together. We know that there is no pre-alignment of the genomic copies, but perhaps alignment occurs before repair takes place. How this happens is a mystery. We wanted to test the possibility of 'post-alignment' (after IR) by tagging a certain locus with GFP and looking at whether we see two dots side by side or fart apart, but the resolution of light microscopy doesn't allow for the GFP foci to be visualized separately.

Box

#115 hrun0815

If you are a student (autodidactic or not) you should know how to quote things. The quotes should be clearly marked as such and they should not be altered — for example by leaving out stuff.

Thank you for the quoting tips.

And your point that as you student your opinion wouldn’t make a difference here is also disingenuous: You specifically asked for clarifications about a point before you voice your opinion. You were given the clarification, but still evade the point.

I still don't understand what was wrong about that text you were pointing to. Generally, I don't have opinion about things I don't understand well. The clarifications you provided were not enough for me to see your point. I don't think my opinion on that issue is important, but if you think it is, you would have to elaborate more on your argument. Again, I don't think that's necessary. It's not a big deal, is it?

In addition, remember that you were the one bemoaning the supposed inability or unwillingness of so-called Darwinists to have a serious discussion. But, clearly by your own admission, it is actually you who is unwilling (or maybe unable since you point to your status as a student).

You seem confused again. Are you referring to my comments addressed to Box? Are you sure you're not misquoting my comments? Apparently, Box was trying to engage in a serious discussion with some folks in this blog, but things didn't seem to go quite right, so I expressed my opinion about discussion requirements. I don't recall saying I was able, capable or willing to engage in serious discussions. Can you show me that text where I said so? If I did, I will correct it. But first, show it to me. It was Box who seemed trying to engage in a deep discussion that was getting nowhere. I know it won't work, so I don't even try. However, if I see signs that it could happen, then I give it a try. But the sign must be very clear. I usually ask a few questions to help my interlocutors to reveal their true motives. If their motives seem sincere and serious, I go ahead with the discussion, assuming I'm interested in the discussed subject. Otherwise, I just skip it or withdraw and move on to something else. My comments were about the need for both parties to be interested in a serious discussion. Both parties mean that both Box and his interlocutors must be willing to mutually benefit from the discussion. That did not seem to be the case. Do you understand this now? I can try to explain it another way, but first let me know if you get it. Thanks. Dionisio

This reminds me of our short discussion, a little over a year ago, on Deinococcus radiodurans. I still hold that this is an extremely claer example of the need for a top-down explanation.

Re-reading this thread, I think I see what you were missing. DNA-repair in in D. radiodurans takes advantage of homologous sequences. There's no need for master plan of the "correct" sequence to aim for, the bits that get joined up are the bits that match each other and so an bind to complimentary sequence. One those overlapping sections are joined up the polymerases can make new double stranded copies. Fig 7 here (pdf) might give you a clearer picture of what's going on wd400

#116 hrun0815

Oh, and re your post 57: it is an iPhone.

Thank you for this information. I forgot to check the post #s on my wife's iPhone and iPad yesterday. Does this mean that MSFT devices work better than Apple gadgets? Well, at least in relation to this particular issue? Hmmm... that's interesting. Dionisio

Oh, and re your post 57: it is an iPhone. hrun0815

Dionisio, I'm neither upset nor confused. If you are a student (autodidactic or not) you should know how to quote things. The quotes should be clearly marked as such and they should not be altered -- for example by leaving out stuff. And your point that as you student your opinion wouldn't make a difference here is also disingenuous: You specifically asked for clarifications about a point before you voice your opinion. You were given the clarification, but still evade the point. In addition, remember that you were the one bemoaning the supposed inability or unwillingness of so-called Darwinists to have a serious discussion. But, clearly by your own admission, it is actually you who is unwilling (or maybe unable since you point to your status as a student). And with that, happy holidays to you, too. hrun0815

To Whom This May Concern Please, don't be upset at my posts. Remember that the OP author, the thread moderator, has the right and the tools to screen out my posts anytime. I will not complain if that happens to my posts. The OP author/ thread moderator also has the right to ask me publicly here or privately by email that I change my posting style or refrain from posting completely. I will quietly obey if that happens to me. But so far, that hasn't occurred, hence I keep posting at my convenience. If someone doesn't like a particular post, write what exactly is wrong with the post or just skip it. Merry Christmas! :) Dionisio

hrun0815 @109

If you mainly hold yourself to fake-quoting work by real scientist, but evade efforts to any clear statements about your opinions then it is no wonder you don’t have to backtrack: just like BA77 you don’t actually say anything of substance to begin with.

You seem a little confused. Let me try to clarify a few things for you. Currently, I'm a student (autodidact), hence my opinion here, where so many folks know much more than I do, would not make any difference. Perhaps one thing I can do is to read what others write and ask questions in order to learn more. Also I like to post here some of the materials I'm reviewing lately, in order to share them with other people who might be interested in the given subjects. These days I'm collecting and organizing research papers with the help of tools like Zotero and Mind Meister, along with WordPress web logs, which I share only with folks that are helping me with my studies or are interested in the stuff I have gathered in there. BTW, I don't recall seeing your answer to my post #57:

#48 hrun0815 Since I don’t have numbered posts on my phone…

Interesting. What kind of phone is that?

I'm just curious. Thanks. Merry Christmas! :) Dionisio

#109 hrun0815 Hey buddy, are you upset at my posts? Calm down, take it easy. It's Christmas season, rejoice! :) Dionisio

Post-translational Regulation of Mitogen-activated Protein Kinase Phosphatase (MKP)-1 and MKP-2 9, 2014, doi: 10.1074/jbc.M114.591925 MAPK phosphatases (MKPs) are critical modulators of the innate immune response, and yet the mechanisms regulating their accumulation remain poorly understood. Interestingly, p38 inhibition prior to LPS stimulation had little effect on MKP-1 and MKP-2 protein levels, but hindered their detection by an M-18 MKP-1 antibody. Remarkably, the stability of both MKP-1 and MKP-2 was markedly decreased in macrophages in the presence of an ERK pathway inhibitor. Surprisingly, enhanced stabilities of the MKP-1 and MKP-2 mutants were not associated with decreased ubiquitination. Our studies suggest that MKP-1 and MKP-2 stability is regulated by ERK-mediated phosphorylation through a degradation pathway independent of polyubiquitination. http://www.jbc.org/content/289/42/28753.short Dionisio

The regulation of BK channel activity by pre- and post-translational modifications doi: 10.3389/fphys.2014.00316 The diversity of BK channel activity results from the considerable alternative mRNA splicing and post-translational modification (e.g., phosphorylation) of key domains within the pore-forming ? subunit of the channel complex. Most of these modifications are regulated by distinct upstream cell signaling pathways that influence the structure and/or gating properties of the holo-channel and ultimately, cellular function. The channel complex may also contain auxiliary subunits that further affect channel gating and behavior, often in a tissue-specific manner. BK channels derive functional diversity through the alternative post-transcriptional splicing of mRNA... The impressive range of phenotypic products that can result from differential splicing of the KCNMA1 gene product contributes to diversity of BK channel function between tissues, cells and intracellular compartments. The molecular mechanisms by which ?-subunits interact with and influence BK channel gating and kinetics are currently an area of active investigation. The dynamic post-translational “tuning” of BK channels permits considerable diversity in the biophysical properties of the current. Their function, however, varies between cell types and layers, and generally is dependent on the associated macromolecular signaling complex. Dynamic regulation of BK channel subunit co-assembly and interaction at the plasma membrane may thus represent a novel paradigm for the modulation of ion channel activity. these studies indicate that the expression and function of BK channels in the vasculature involves complex expression and signaling pathways, and may vary between cells, tissues, vascular beds and pathophysiological profiles. Heteromeric BK channel complexes are the subject of extensive post-translational modifications, which can significantly alter channel behavior. Some modifications are highly-complex and require prior upstream modification(s) to the channel subunits. observations suggest that constitutive phosphorylation may help stabilize BK channel tertiary structure and/or create binding sites for interacting proteins. The various protein kinases responsible for these in vivo modifications are presently unknown, as is the extent to which channels from other tissues or expressed heterologously exhibit constitutive phosphorylation. Future studies examining the direct phosphorylation of native BK channels by tyrosine kinases in situ are needed to clarify the physiologic importance of this regulatory event. Protein ubiquitination has emerged as a ubiquitous quality control mechanism for the regulation of protein trafficking and turnover and has been implicated in the dynamic control of diverse cellular processes (e.g., gene transcription, synaptic development and plasticity, oncogenesis, etc.) Recent evidence indicates that BK channels also undergo ubiquitination, which appears to have important functional implications. BK channel activity is regulated both directly and indirectly through a diverse range of modulatory pathways involving covalent modifications, metabolic factors, trafficking events and transcriptional processes... BK channels represent powerful effectors in tissue health and dysfunction and that understanding their modes of regulation may lead to novel therapeutic strategies in disease treatment. http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00316/full Dionisio

And even more links with quotes (that by the way are somewhat modified yet taken more or less verbatim without being marked as such) from Dionisio. Again a good indicator who is interested in serious discussion. And another thing is pretty funny, too. It's no wonder that you can brag to Box about how you supposedly never had to backtrack.

I don’t recall any instance where I had to backtrack when discussing anything with our ‘n-D e’ interlocutors.

If you mainly hold yourself to fake-quoting work by real scientist, but evade efforts to any clear statements about your opinions then it is no wonder you don't have to backtrack: just like BA77 you don't actually say anything of substance to begin with. hrun0815

So Joe, I take it you are unable to find a scientific source that only claims ATP synthase evolved and does not provide evidence for this claim? Got it. Here's some things you can look at that talk about the evolution of ATP synthase: Rotary DNA motors Doering C, Ermentrout B, Oster G Ectopic bold beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis Martinez LO ATP synthases: structure, function and evolution of unique energy converters. Müller V, Grüber G Evolution of the F0F1 ATP synthase complex in light of the patchy distribution of different bioenergetic pathways across prokaryotes. Koumandou VL, Kossida S Bioenergetics: the evolution of molecular mechanisms and the development of bioenergetic concepts. Skulachev VP1 DNA sequence of a gene cluster coding for subunits of the F0 membrane sector of ATP synthase in Rhodospirillum rubrum. Support for modular evolution of the F1 and F0 sectors. Falk G, Walker JE. I suggest that you and your friends stop falling back on the argument that "evolution hasn't explained this, so evolution must be wrong." It just makes you look like a bunch of idiots to those who actually know what they're talking about. Also, it's not that evolution can't be modeled, the problem is it is too complex a process for us to successfully model right now. AVS

AVS, there isn't any evidence that natural selection can produce any ATP synthase. There isn't any evidence that unguided evolution can produce anything beyond disease and deformities. Joe

Unguided evolution can't even be modeled. It is unscientific. Joe

With or without natural selection. Doesn't matter mungy. Just want to see the claim made without any evidence provided. I doubt you'll be able to find it seeing as science (including evolution =) ) is based on claims that are supported by evidence. Unlike ID. AVS

AVS must agree that there isn't any evidence for natural selection producing any ATP synthase. And seeing tat unguided evolution doesn't have any other creative mechanism AVS must also agree that unguided evolution is unscientific. This is a good day Joe

Post-translational mechanisms related to PAR-4 regulation doi: 10.1158/1538-7445.AM2014-3386 Further analyses of the post-translational mechanisms involved in cl.PAR-4 activity still need to be investigated to better understand the regulation of this potential tumor suppressor. http://cancerres.aacrjournals.org/content/74/19_Supplement/3386.short Dionisio

Translational and Post-Translational Regulation of XIAP by eIF2? and ATF4 promotes ER stress-induced Cell Death during the Unfolded Protein Response doi: 10.1091/mbc.E13-11-0664 ER protein misfolding activates the Unfolded Protein Response (UPR) to help cells cope with ER stress. If ER homeostasis is not restored, UPR promotes cell death. The mechanisms of UPR-mediated cell death are poorly understood. http://www.molbiolcell.org/content/early/2014/03/10/mbc.E13-11-0664.abstract Dionisio

Well Joe, AVS got you there. If no scientist ever claimed that ATP synthase evolved it follows that no scientist ever claimed that ATP synthase evolved by the process of natural selection. Mung

Joe according to you, scientists have made the claim that ATP synthase evolved by the process of natural selection, yet these scientists failed to provide evidence of this claim. I am simply asking for one example of this. If you can't provide a single example to back up what you said, then feel free to retract your statement. AVS

AVS:

Can you point me to a piece of scientific literature that says “natural selection can produce protein complexes like ATP synthase” without providing any evidence?

Can you show me ONE in which they do? What other creative mechanism do you have? Natural selection is the only one I am aware of. Joe

Post-translational Regulation of the Gamete Fusogen GCS1 doi: 10.1128/EC.00330-13 Recent studies of the gamete fusogen GCS1/HAP2 indicate that this protein is deeply conserved across eukaryotes, and its exclusive and/or functional expression generally resides in males or in male homologues. However, little is known regarding the conserved or primitive molecular traits of males and females within eukaryotes. http://ec.asm.org/content/early/2014/03/10/EC.00330-13.abstract Dionisio

Ok, let's start with the first one. Can you point me to a piece of scientific literature that says "natural selection can produce protein complexes like ATP synthase" but does not provide any evidence for this claim? AVS

AVS:

Can you give me an example of “what they say without evidence?”

That natural selection can produce protein complexes like ATP synthase. That universal common descent is a fact when they don't even know A) what makes an organism what it is and B) can't get beyond populations of prokaryotes given starting populations of prokaryotes without making magical claims. That is a start Joe

Post-translational regulation of COX2 activity by FYN While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1983 Dionisio

Wow, you should make a list of those 400 PTMs and post them. That would be very useful. AVS

Post-translational modifications, or PTMs, create the enormous structural and functional diversity required to integrate information regarding the nutrient/stress status of the cell and regulate essential cellular functions. There are more than 400 known PTMs, and, almost without exception, virtually all polypeptides are post-translationally modified. https://www.asbmb.org/asbmbtoday/201402/ SpecialSymposiaSeries/PostTranslation/ Dionisio

Can you give me an example of "what they say without evidence?" AVS

AVS:

I think it’s funny how certain people here rely almost entirely on scientists to “prove their point” via direct copy/paste, and yet these certain people are also so comfortable disagreeing with these scientists on evolution.

Yes we agree with what they can demonstrate and are skeptical of their claims that they cannot even model. What they say without evidence can be dismissed without evidence. Joe

I think it’s funny how certain people here rely almost entirely on scientists to “prove their point” via direct copy/paste, and yet these certain people are also so comfortable disagreeing with these scientists on evolution. Watching IDers trying to talk about science is like watching a dog chase its tail. AVS

Roles and post?translational regulation of cardiac class IIa histone deacetylase isoforms doi: 10.1113/jphysiol.2014.282442 Although considerable progress has been made in understanding the roles of post?translational modifications (PTMs) such as phosphorylation, oxidation and proteolytic cleavage in regulating class IIa HDAC localisation and function, more work is required to explore the contributions of other PTMs, such as ubiquitination and sumoylation, as well as potential cross?regulatory interactions between distinct PTMs and between class IIa and class I HDAC isoforms. http://jp.physoc.org/content/early/2014/11/27/jphysiol.2014.282442.abstract Dionisio

Regulation of pannexin channels by post-translational modifications DOI: http://dx.doi.org/10.1016/j.febslet.2014.01.028 The large-pore channels formed by the pannexin family of proteins have been implicated in many physiological and pathophysiological functions, mainly through their ATP release function. However, a tight regulation of channel opening is necessary to modulate their function in vivo. Post-translational modifications have been postulated as some of the regulating mechanisms for Panx1, while Panx2 and Panx3 have not been as well characterized. Positive regulators include caspase cleavage to open Panx1 channels in apoptotic cells, and activation by Src family kinases via ionotropic receptors in neurons and macrophages. S-nitrosylation of cysteines has been shown to both inhibit and activate the Panx1 channel in different cell types. All three pannexins are N-glycosylated but to different levels of modification. Their diverse glycosylation appears to regulate cellular localization, intermixing, and may restrict their ability to function as inter-cellular channels. It is clear that our understanding of pannexin post-translational modification and their role in channel function regulation is still in its infancy even a decade after their discovery. http://www.febsletters.org/article/S0014-5793(14)00057-X/abstract Dionisio

"I also think it’s somewhat amazing that someone could cover the “News” desk at this site for so long without picking up even the most elementary understanding of biology." Funny, people talking about biology here and yet not actually knowing or learning anything seems to be a common theme. AVS

Surf the Post-translational Modification Network of p53 Regulation doi:10.7150/ijbs.4283 Among the human genome, p53 is one of the first tumor suppressor genes to be discovered. It has a wide range of functions covering cell cycle control, apoptosis, genome integrity maintenance, metabolism, fertility, cellular reprogramming and autophagy. Although different possible underlying mechanisms for p53 regulation have been proposed for decades, none of them is conclusive. While much literature focuses on the importance of individual post-translational modifications, further explorations indicate a new layer of p53 coordination through the interplay of the modifications, which builds up a complex 'network'. This review focuses on the necessity, characteristics and mechanisms of the crosstalk among post-translational modifications and its effects on the precise and selective behavior of p53. Although relatively unified findings related to the functions of post-translational modifications (PTMs) were obtained in vitro, the in vivo data are somehow contradictory, indicating a variable behavior of p53. Overall, PTM exerts both general and distinctive role in regulating p53 behavior. However, the contradictions between the results of the in vitro and in vivo experiments call for more in-depth studies and raise some open problems concerning the real regulatory network of PTMs. Promising as the 'code' model of p53 PTM is, the following questions remain open such as: what is the real basis for the redundancy of the individual modifications in vivo? What is the real mechanism that regulates the context-dependent behavior of p53? How exactly is p53 involved in the regulation of one specific biological effect? How general is the mechanism for the regulation of PTM and in what way do they really cooperate? With the emergence of the novel functions regulated by p53, such as metabolism and nutrient stress responses, is there a possibility to revise the demarcations between different phenotypic outcomes to a more subtle one? In order to tackle these problems, numerous further investigations are required: (i) more precise and subtle distinction of the effects of the 'code' in molecular level instead of phenotypic level; (ii) discrimination between the direct and indirect effects of specific modifications; (iii) identification of the combinatorial behaviors of the modifications using high-throughput testing method; (iv) in situ observation of the dynamic changes of the modifications marks using more reliable and direct time-resolved method. Although there is still a long way to go, it is believed that the final decipherment of the p53 code will arrive in the near future. http://www.ijbs.com/v08p0672.htm Dionisio

Dionisio at 73:

#61 hrun0815 So far researchers are working hard trying to figure out how all those complex mechanisms work and what they do. Not much talk about how all the required pieces of the puzzle got there, in the right place, at the right time, to begin with. We’re talking about a number of different mechanisms. Have you seen any serious documentation describing that anywhere lately?

Hah. This is utterly amusing. Let's revisit my post #32:

Ahh, Box, the silly ‘you can’t explain ultimate causes so how dare you point out that some statement is stupid’?

It looks like sooner or later 'ultimate causes' are the escape hatch for many. Rather than explaining why are are posting all those clipped research results, or rather than telling us if you agree that the OP is hopelessly mangled, or rather than telling us if you agree with WD400's explanation why these statements are stupid, or rather than clarifying which question of the many you posed you actually wanted to discuss, ... you now want to know how everything got there to begin with. This is particularly interesting in light of your post #38:

Any attempt to have a meaningful discussion between two irreconcilable worldview positions fails before it starts, unless both parties are really interested in having a serious discussion, where the ultimate goal is to find the truth about the discussed subject. Obviously that’s not what is happening in this case. Your interlocutor along with his comrades and fellow travelers don’t seem interested in any serious discussion. Their motivations are not clear, but they don’t seem to be serious. That’s why they point to obscure issues related to the OP.

hrun0815

Dionisio at 58:

#55 wd400 I was expecting hrun0815 to respond, but it’s nice to get a little help from a friend. Anyway, thank you for expressing your opinion on the given subject.

You are confused. This is not me getting 'help' other than that I don't have to type what WD400 typed in 55. WD400 was not expressing on opinion. He was making statements of fact. Do you dispute the facts? Or do you still maintain that you can't make a decision unless I read and respond to your questions first? By the way, I still don't know exactly which would be the key question that you are interested in. hrun0815

Dionisio at 67:

Read those reports carefully, paying attention to the words and their meaning. Also see post #66. It may answer some of your questions. Have a good week. Ciao amico !

I see, you can post a single post five times, but it is too difficult to use your own words to describe what you actually mean? Why are you posting all these references to investigations of post-transcriptional gene expression when the criticism is that the work does NOT suggest there is a as-of-yet unidentified mechanism? (By the way, I have no doubt that many aspects of gene regulation pre- or post-transcription have yet to be described, but this work does not suggest any such a thing.) hrun0815

Box at 64: I truly don't get any of the three statements you made here. hrun0815

WD400: So, when DNA damage is detected the cell cycle is arrested, the organism needn’t know why a given cell is damaged.

This reminds me of our short discussion, a little over a year ago, on Deinococcus radiodurans. I still hold that this is an extremely claer example of the need for a top-down explanation. Dionisio, you may be interested too. Maybe I have more time tomorrow. Have to run. Box

Box However it is also clear that there must also be a multitude of non-standard replies of an organism. Not really, cells/organisms can react to certain stimuli. So, when DNA damage is detected the cell cycle is arrested, the organism needn't know why a given cell is damaged. Other gene regulatory networks work in similar ways, which is why some biological responses are in fact counter-productive (inflamation response, auto-immune diesaes, so called super-normal stimuli...) Slijper's goat is very interesting, but as an example of developmental plasticity and interaction of genotype and environment, rather than evidnce for some elan vital directing an organism. If an organism could really "subject its parts to its will", then whence cancer? Couldn't the organism just tell those cells to stop dividing? wd400

#72 Box

WD400 #69, You are correct, I misunderstood your example.

Box, you better watch out. You just wrote that wd400 is correct and that you misunderstood his example. You were confused on a simple case of the widely known lac operon. That could happen to anyone, including me, but so far, it hasn't happen to me. I don't recall any instance where I had to backtrack when discussing anything with our 'n-D e' interlocutors. Maybe because I ask them more questions than they can answer? Dunno. But don't recall that happening yet. Your holistic approach makes sense, but perhaps it is too rigid in the way you present it. I try to use the available information, in the research reports, and go from there, asking all kinds of questions about the systems described by those reports. Soon the systemic characteristics pop up in the discussion. Basically, I take what is available, and move on from there. Soon the interrelationship with other parts appear as missing links. Remember we are not designing anything, but detecting design. In order to detect design in any system, the investigation doesn't have to be top-down. We could start from any part of the whole system, investigate how it functions in details and detect top-down design, because soon we'll notice signals coming from external sources and going to external recipients, hence we'll include that external object in the investigation and continue, till we detect another external source/recipient and so on. I believe the top-down design decisions were made a priori, when the whole system was setup. Do you see my point? Dionisio

#76 Box

I reject a mechanical or computerish concept of an organism. In my book an organism is a whole. And this whole is capable of downward causation – an organism can subject its parts to its will. What we see here is an organism that makes the best of what is available – IOW downward causation. I hold that this capability is inherent to life and cannot be explained bottom-up.

Where do you see any bottom-up implication in my reference to mechanisms? Did you notice that as they research the mechanisms, new issues appear all over? Dionisio

Box What we see in most research reports are descriptions of the current mechanisms, though still missing many details. What the interlocutors should produce is a link to any documentation containing a detailed description of hypothetical processes leading to setup the mechanisms that operate within the cells in all scenarios. Dionisio

Dionisio #74

Dionisio: The decision making processes are mostly embedded within the complex mechanisms, which are setup to handle many different situations, depending on the surrounding circumstances, including stochastic scenarios.

I reject a mechanical or computerish concept of an organism. In my book an organism is a whole. And this whole is capable of downward causation - an organism can subject its parts to its will. A striking example is the case of Slijper’s goat:

Slijper's two-legged goat was born with a congenital defect of the front legs so that it could not walk on all fours, and so it learned to walk and run by using its hind legs alone. Then, when it died an accidental death, Slijper dissected it and documented remarkable changes in muscle and bone, including striking changes in the bones of the hind legs; the leg muscles, including a greatly thickened and elongated gluteal tongue and an innovative arrangement of small tendons, a modified shape of the thoracic skeleton, and extensive modifications of the pelvis. [West-Eberhard]

What we see here is an organism that makes the best of what is available – IOW downward causation. I hold that this capability is inherent to life and cannot be explained bottom-up.

Dionisio: The real question is how were those complex mechanisms put into place and setup to begin with.

That is another important question, but in my opinion a less profound one. Box

hrun0815 Did you see post #57? I'm just curious. Thank you. Dionisio

Box, The decision making processes are mostly embedded within the complex mechanisms, which are setup to handle many different situations, depending on the surrounding circumstances, including stochastic scenarios. Scientists don't understand many of those mechanisms yet. That's what they're working hard on. As you can read in some reports, many things remain poorly understood. To make things worse, as they dig deeper into those mechanisms, new issues appear. The real question is how were those complex mechanisms put into place and setup to begin with. Has anyone seen that building process described in details? Can we have a link to that documentation? Do you see what I mean? Dionisio

#61 hrun0815 So far researchers are working hard trying to figure out how all those complex mechanisms work and what they do. Not much talk about how all the required pieces of the puzzle got there, in the right place, at the right time, to begin with. We're talking about a number of different mechanisms. Have you seen any serious documentation describing that anywhere lately? Dionisio

WD400 #69, You are correct, I misunderstood your example. Of course I do not wish to argue that there are no standard replies of an organism to certain environmental stimuli. It's clear that they exist. However it is also clear that there must also be a multitude of non-standard replies of an organism. Every organism will be confronted with new things and will be forced to improvise - IOW make decisions. Stephen L. Talbott put it like this:

But the same mystery plays out in the mature organism, which must continually work to maintain its normal form, as well as restore it when injured. It is difficult to bring oneself fully face to face with the enormity of this accomplishment. Scientists can damage tissues in endlessly creative ways that the organism has never confronted in its evolutionary history. Yet, so far as its resources allow, it mobilizes those resources, sets them in motion, and does what it has never done before, all in the interest of restoring a dynamic form and a functioning that the individual molecules and cells certainly cannot be said to “understand” or “have in view”. We can frame the problem of identity and context with this question: Where do we find the context and activity that, in whatever sense we choose to use the phrase, does “have in view” this restorative aim? Not an easy question. Yet the achievement is repeatedly carried through; an ever-adaptive intelligence comes into play somehow, and all those molecules and cells are quite capable of participating in and being caught up in the play.

Box

Dionisio: In the atheistic worldview paradigm, many times the cause-effect relationship may have nothing to do with responsibilities or decision making. They believe that many times things just happened, happen and will happen, depending on the surrounding circumstances. It’s that simple. It’s a belief system.

I'm no longer sure what their concept of life is. You seem to be perfectly right when you summarize: "things just happened, happen and will happen, depending on the surrounding circumstances". Thank you for your story.

Dionisio: English is not my first language.

I haven't noticed, but that implicit compliment doesn't hold much weight, because English is not my first language either. :) Box

Posttranslationally modified tubulins and other cytoskeletal proteins: their role in gametogenesis, oocyte maturation, fertilization and Pre-implantation embryo development. doi: 10.1007/978-1-4939-0817-2_4. The cytoskeleton, mainly consisting of microtubules, intermediate filaments and microfilaments, along with cytoskeleton associated and interconnecting proteins as well as the centrosome, plays enormously important roles in all stages of embryogenesis and undergoes significant changes to accommodate a diversity of cellular functions during gametogenesis, oocyte maturation, fertilization and pre-implantation embryo development. The varied functions of the cytoskeleton can be accomplished on many different levels, among which are a diversity of different posttranslational modifications (PTMs), chemical modifications that regulate activity, localization and interactions with other cellular molecules. PTMs of the cytoskeleton, including phosphorylation, glycosylation, ubiquitination, detyrosination/tyrosination, (poly)glutamylation and (poly)glycylation, acetylation, sumoylation, and palmitoylation, will be addressed in this chapter. Focus will be on (1) Microtubules, microtubule organizing centers (centrosomes), intermediate filaments, microfilaments and their PTMs; (2) Cytoskeletal functions and cytoskeletal PTMs during gametogenesis and oocyte maturation; and (3) Cytoskeletal functions and cytoskeletal PTMs during fertilization and pre-implantation embryo development. http://www.ncbi.nlm.nih.gov/pubmed/25030760 Dionisio

I don't think you understand, the lac operon example shows how specific genes are expressed in response to the presence of lactose. If a decision is being made then the description I gave you is that decision. wd400

wd400, You described how gene expression can be switched from “off” to “on”. My question pertains to where the decision is made which gene to switch off or on and when. The right choice is crucial for the survival of any organism. One thing we seem to agree upon: the decision cannot be made by molecules. Why do we agree? From my part I would say: because molecules lack overview. They cannot be trusted not to make a mess of things.

wd400: what’s materialism got to do with it

Under materialism there are only molecules (fermions and bosons to be precise). So how come there isn't a mess? Box

#61 hrun0815 Read those reports carefully, paying attention to the words and their meaning. Also see post #66. It may answer some of your questions. Have a good week. Ciao amico ! Dionisio

#60 Box In the atheistic worldview paradigm, many times the cause-effect relationship may have nothing to do with responsibilities or decision making. They believe that many times things just happened, happen and will happen, depending on the surrounding circumstances. It's that simple. It's a belief system. Their bottom line is that matter can be transformed into energy and vice versa, but it can't be created or destroyed. It always was and always will be. Then through some still unknown processes things got to their current state. If you ask the 'third way' folks, they would give you a different account of the hypothetical events, than the orthodox 'n-D e' folks would. There are as many variations of that fairytale story as promoters. :) I don't know which party line our interlocutors adhere to. Perhaps it's a hybrid of the 'n-D e' and the 'third way' approaches. It doesn't matter. At the end of the day it's all the same garbage. :) It's easy for me to wear an atheist hat. All I have to do is dust my old one. See, I've been there, done that, bought the shirt, wore it. Before I got my engineering degree, I had to pass a comprehensive exam on dialectic materialism and all that paraphernalia. It was a requirement. No excuses were accepted. Back then I believed all that garbage. They served it without ketchup or mustard, but it tasted good. Pathetic, but that's how it was. Now you see why these new 'baby' atheists don't impress me at all. In a way I could lecture them on their own stuff, but I really don't care much about it anymore. Now I've got much better things to do than to squander my limited time on senseless discussions with those confused folks. I just pray that some of them will see reality as is, not through the distorting lenses they wear now. :) I've taken online classes on biology, provided by some universities. Currently I'm studying some of the detailed reports coming out of research, in order to understand the detailed mechanisms associated with cell fate specification and determination. The idea is to develop educational software using the same interactive 3D technology used in computer games. Sometimes I look into other related issues, like neuroscience, regulatory networks, signaling pathways, etc. It's all very difficult and challenging, but highly fascinating. Now I'm using a combination of Mind Meister + Zotero + interconnected WordPress restricted web logs, in order to gather and organize the information, which is overwhelming. Many times I share some of the references to the resources here in this site, mostly in the 'third way' thread and a couple other threads. Sometimes I take breaks away from the intensive studying and come to this blog to see what's going on here and maybe get involve in a discussion for a short while, until I feel it's time to quit and go back to work on the real stuff. It's an interesting experience too. I've learned a few things from gpuccio and other folks here. Also got exposed to many different writing styles. English is not my first language. :) Kind regards. Dionisio

I described how the gene expression can be switched from "off" to "on". If you call that a "decision", then I don't see that any one molecule made it. If you don't call that a decision then the phenomenon you asked to be explained can be achieved without a decision being made. I don't think you really have trouble what a cell is, do you? And what's materialism got to do with it, unless ID is trying to back biology back further than I thought by resurrecting vitalism? wd400

WD400, hrun0815.

hrun0815: So of course I mean ONLY.

Does information behave in accord with rules of physical chemistry?

hrun0815: (...) the answer is the interactions of a bunch of different molecules present at a given time.

I fail to grasp why anyone would think that this constitutes an answer.

Box: (...) what is responsible for the decision to do so? The cell?

wd400: Sure, why not?

What is "the cell" under materialism? Explain why it can make decisions and its constituent molecules not. Box

“Suppose a unicellular organism. When certain proteins slide a spool along the DNA, exposing base pairs for gene expression, what is responsible for the decision to do so? The cell

Sure, why not? Take the classic example from Biochem101, the lac operon. You have DNA encoding a protein which (a) bind to region of DNA near som other genes, preventing RNA Pol from transcibing them and (b) can bind to an environmental chemical (a metabolic product of lactose). When it binds to lactose the shape is altered such that it no longer blocks expression of the other genes, and so the cell create mRNA from the rest of the lac genes. Nothing in that sounds like a decision molecule, but gene expression has started. (there's much more to the lac operon, but the example should serve to show how these things can work) wd400

Box: "If you mean “only according to rules of physical chemistry” then yours is a statement of faith. One could argue that at the moment of death molecules start acting (only) according to rules of physical chemistry and notably according to the second law, which informs us that things tend to descend into chaos." I have no idea why that would be a statement of faith? If you are alluding that there might be some 'immaterial' influence on molecules in addition to basic physical chemistry (and of course at a smaller level physics proper) then you are venturing outside to what science can investigate. So of course I mean ONLY. "Suppose a unicellular organism. When certain proteins slide a spool along the DNA, exposing base pairs for gene expression, what is responsible for the decision to do so? The cell?" It depends on what you mean by 'is responsible for the decision'. If you mean in the same way that we think of, for example humans making choices then the answer is nothing and nobody. If you mean 'how come this is happening at this time' then the answer is the interactions of a bunch of different molecules present at a given time. Remember that for example the same action can occur when just a few molecules happen to be in close proximity to each other and are present at the right concentration. "Indeed, but the vast majority of ID supporters is aware of the fact that information cannot make decisions." I'm failing completely to guess what you mean here. I think everybody agrees that information cannot make decisions. What this has to do with scientists, ID, or Systems Biology is not clear to me. hrun0815

Dionisio, I don't understand why exactly you are pointing to published aspects of post-transcriptional regulation? This is exactly the point: why do you think the data points to an as-of-yet undiscovered mode of regulation? hrun0815

WD400: DNA is the closest thing to a “master molecule”, since it encodes the proteins that regulate the expression of DNA, (...)

The Selfish Gene (1976).

WD400: but biological systems are just that: systems arising from the action of many different classes of molecules and the environment.

What is the "system" under materialism? Emergent property?

WD400: There is no reason to think a single type of “decision molecule” is required, so far as I can see.

Maybe you can answer my question from post #45: "Suppose a unicellular organism. When certain proteins slide a spool along the DNA, exposing base pairs for gene expression, what is responsible for the decision to do so? The cell?" Box

Post-translational modification and regulation of actin. doi: 10.1016/j.ceb.2012.10.009. Many of the best-studied actin regulatory proteins use non-covalent means to modulate the properties of actin. Yet, actin is also susceptible to covalent modifications of its amino acids. Recent work is increasingly revealing that actin processing and its covalent modifications regulate important cellular events. In addition, numerous pathogens express enzymes that specifically use actin as a substrate to regulate their hosts' cells. Actin post-translational alterations have been linked to different normal and disease processes and the effects associated with metabolic and environmental stressors. Herein, we highlight specific co-translational and post-translational modifications of actin and discuss the current understanding of the role that these modifications play in regulating actin. http://www.ncbi.nlm.nih.gov/pubmed/23195437 Dionisio

#55 wd400 I was expecting hrun0815 to respond, but it's nice to get a little help from a friend. Anyway, thank you for expressing your opinion on the given subject. :) Dionisio

#48 hrun0815

Since I don’t have numbered posts on my phone...

Interesting. What kind of phone is that? My Nokia Lumia 635 does show the post #s within the thread. Any idea why they don't show up on your phone? Also I use a MSFT Surface tablet, which shows the post #s fine. I'll check my wife's iPhone later to see if the post #s appear. Also will check that on her iPad. We didn't buy these gadgets. Someone gave them to us as presents on separate occasions. I don't use the Nokia Lumia as phone, but as WiFi device. My phone is a $15 ZTE Z222 flip device that works just fine and fits in my pocket very easily. :) It's kind of funny, my wife ended up with Apple gadgets and I got mine from Mr. Softy (except the flip phone). But we get along very well. :) Dionisio

box,

This matter goes to the heart of materialism. If one’s ambition is to reduce an organism to matter, then one has to look for material regulators with decision power – IOW decision-molecules.

Why do you think this is true? DNA is the cloest thing to a "master molecule", since it encodes the proteins that regulate the expression of DNA, but biological systems are just that: systems arising from the action of many different classes of molecules and the environment. There is no reason to think a single type of "decision molecule" is required, so far as I can see. wd400

Ok, what is wrong with the first statement?

Well, the fact this result relates in no way to any RNA world hypthesis is certainly a problem, don't you think. I also think it's somewhat amazing that someone could cover the "News" desk at this site for so long without picking up even the most elementary understanding of biology.

What is it that you don’t like about the second statement?

There are many known modes of post-transcriptional and post-translation regulation already known. We could, of course, stand to learn more about these important processes by it's not like we are starting from nothing. wd400

#40 hrun0815

the two statements are: “Interesting, when we consider the high hopes placed in RNA world.” and “The findings point to a yet-unidentified cellular mechanism that regulates gene expression…”

Ok, what is wrong with the first statement? What is it that you don't like about the second statement? Dionisio

"Take it easy, buddy. One step at a time. No rush. Ok?" Really? "Did you answer my 4 questions written in post #36? I don’t recall seeing your answers." In other words, before you answer a simple point that post 1 and post 3 in this thread made I will have to jump through hoops and answer your four questions? Because without an answer to your questions you don't know what I'm asking you to agree on? That seems all a bit disingenuous to me. But so be it: Since I don't have numbered posts on my phone, could you repeat the question(s) you have? I would pick just one, because generally once you start discussing a single question there is hardly any room for anything else. And maybe you can keep in mind to at some point come back to my question/points that clearly preceded yours. :) hrun0815

#40 hrun0815 Sorry, I didn't notice you wrote to me in a post you initially addressed to Box. Kind of confusing. Please, can you address me on separate posts? I'll appreciate it. Dionisio

hrun0815 @41 I’m certainly happy to try and answer questions you might have.

Why didn’t you answer the easy questions written for you in my post #36? I've repeated the question about the questions you didn't answer in post #36, in order to increase the probabilities that you see it. :) Let's see, maybe this time you won't skip it. :) Dionisio

hrun0815 @41 I’m certainly happy to try and answer questions you might have.

Why didn’t you answer the easy questions written for you in my post #36? Dionisio

41 hrun0815 I’m certainly happy to try and answer questions you might have.

Why didn’t you answer the easy questions written for you in my post #36? Dionisio

@41 hrun0815 I’m certainly happy to try and answer questions you might have.

Why didn’t you answer the easy questions written for you in my post #36? Dionisio

#41 hrun0815 I’m certainly happy to try and answer questions you might have.

Why didn’t you answer the easy questions written for you in my post #36? Dionisio

#41 hrun0815 I’m certainly happy to try and answer questions you might have.

Why didn't you answer the easy questions written for you in my post #36? Dionisio

hrun0815: As for what materialists believe it look for- I’m not sure there is a single answer. But for the current scientific endeavor it is pretty clear that scientists are looking how large ensembles of molecules, each acting according to rules of physical chemistry, (…)

If you mean “only according to rules of physical chemistry” then yours is a statement of faith. One could argue that at the moment of death molecules start acting (only) according to rules of physical chemistry and notably according to the second law, which informs us that things tend to descend into chaos.

hrun0815: (...) end up ‘making decisions’ on a larger level (e.g. as organelles, cells, organs, or organisms).

Suppose a unicellular organism. When certain proteins slide a spool along the DNA, exposing base pairs for gene expression, what is responsible for the decision to do so? The cell?

hrun0815: That, taken to the point, is the very essence of Systems Biology that many ID supporters appear to be pretty find of.

Indeed, but the vast majority of ID supporters is aware of the fact that information cannot make decisions. Box

#43 hrun0815 Take it easy, buddy. One step at a time. No rush. Ok? Before I agree on anything, I want to understand exactly what it is I'm agreeing on. Did you answer my 4 questions written in post #36? I don't recall seeing your answers. :) Dionisio

Dionisio, just to reply to this real quick: "That’s why they point to obscure issues related to the OP." If you find the point that phys.org is a terrible source for science information or the point that News takes something terrible and makes it even worse an obscure issue then so be it. I don't know how to actually have a serious discussion if you are talking with somebody who can't even agree on this relatively simple matter. Do you agree? Do you, Box? And why would you not be willing or able to clarify this point with a even a single word before moving on? hrun0815

Box, of course no materialist would not look for 'a decision molecule'. If there was such a molecule how would you propose or could make a decision. Now a non-materialist could simply posit that the molecule has a soul or that some non-material entity acts by manipulation this magical molecule, but I guess that is not a commonly held view. As for what materialists believe it look for- I'm not sure there is a single answer. But for the current scientific endeavor it is pretty clear that scientists are looking how large ensembles of molecules, each acting according to rules of physical chemistry, end up 'making decisions' on a larger level (e.g. as organelles, cells, organs, or organisms). That, taken to the point, is the very essence of Systems Biology that many ID supporters appear to be pretty find of. hrun0815

Dionisio, I'm certainly happy to try and answer questions you might have. I'd suggest to start small: pick one or two questions, ideally not something that requires chapters or whole books to answer, and if you want something concrete try to stick with factual questions rather than those that require philosophical musings. hrun0815

Box, if you consider the point of my post that you initially commented on 'some unrelated matter', then indeed it is probably pointless to continue. Dionisio, the two statements are: "Interesting, when we consider the high hopes placed in RNA world." and "The findings point to a yet-unidentified cellular mechanism that regulates gene expression..." hrun0815

#38 Dionisio, For some reason, I also tend to believe that hrun0815 is a materialist. If that is indeed the case, then he said something very untypical:

hrun0815: Of course we do not expect to find a ‘decision mole Ike’ [decision-molecule] and the very notion is indeed absurd. I’ve never heard of any scientist looking for it either. Have you? [my emphasis]

This matter goes to the heart of materialism. If one's ambition is to reduce an organism to matter, then one has to look for material regulators with decision power - IOW decision-molecules. Now hrun0815 tells me that "of course" there is no such thing and that scientists never looked for such a thing. Moreover he states that the very notion is "absurd". I can easily agree with his statement that the notion of a decision-molecule is absurd, but only because I'm no materialist. The question is: how can a materialist hold that the notion of a decision-molecule is absurd? If molecules are not making the decisions, then what is behind the steering wheel? Box

#37 Box

I’m interested to read your view on the matter. However if you insist on agreement on some unrelated matter, then discussion ends here.

Perhaps your discussion with your interlocutor ended before it could start. Any attempt to have a meaningful discussion between two irreconcilable worldview positions fails before it starts, unless both parties are really interested in having a serious discussion, where the ultimate goal is to find the truth about the discussed subject. Obviously that's not what is happening in this case. Your interlocutor along with his comrades and fellow travelers don't seem interested in any serious discussion. Their motivations are not clear, but they don't seem to be serious. That's why they point to obscure issues related to the OP. Dionisio

hrun0815, I don't wish to opine on phys.org or the alleged methods by news.

hrun0815: If we agree on that then we could go on and discuss what scientists are looking for.

I'm interested to read your view on the matter. However if you insist on agreement on some unrelated matter, then discussion ends here. Box

#35 hrun0815 Please, can you point to the exact statement(s) that you don't like in the OP? Can you quote it (them)? Thanks. Did you read the reports that were referenced in previous posts in this thread? They seem to confirm what the OP indicated. Do you see it differently? I have very specific questions to ask the scientists who worked on the referenced reports. Do you want to try answering my questions? Are you qualified to answer them? I'll give you a hint. See the text in bold characters in my previous posts. Some of my questions might be related to the bold text. Wanna try? :) Dionisio

Box, before we go on could we get back to the original point of my post? Do you agree that if you rely on poor science aggregators like Phys.org or worse still on the mangled science comments of News, then you will be badly misinformed (like both WD400 and my original post point out)? Do you agree that if you actually want to take anything away from this you'll have to go to the original article and actually read it? If we agree on that then we could go on and discuss what scientists are looking for. (I presume you meant 'they' or 'the scientists' rather than 'we' in your last post.) hrun0815

#33 Box

what are we looking for?

Interesting question. It seems like science researchers are trying to figure out how things work in biology, so we can have better medical treatments and more effective health maintenance plans. However, it also seems like the ultimate answers keep eluding the researchers. As they answer some of the outstanding questions, new ones pop up. Kind of like a never ending story. Like the Energizer bunny, it just keeps going, and going... :) But in the meantime the research reports shed light on the elaborate systems they try to describe. And guess what? They look more interesting than before the reports were published. New unknowns appear. Perhaps that's one of the reasons why we read so many times words like 'unexpected', 'surprising', etc. in some of those reports. Then we ask what did they expect? No idea. Now, that's really cool. Isn't it? :) Perhaps that's why some folks didn't like the OP in this thread. It made them feel itchy. But that's their problem, not yours. :) We look forward, with much anticipation, to reading newer reports coming out of research. We ain't seen nothing yet. This party is just starting. The fun part is still ahead. Enjoy it! :) Dionisio

hrun0815: Of course we do not expect to find a ‘decision mole Ike’ and the very notion is indeed absurd. I’ve never heard of any scientist looking for it either. Have you?

There was a time that the DNA-molecule was a likely candidate. Scientists aren't exactly trying to show that 'everything is interconnected', right? They want to find 'the regulator', don't they? If there are no molecules with decision-power, and if the very notion is indeed absurd, then, pray tell, what are we looking for? Box

Ahh, Box, the silly 'you can't explain ultimate causes so how dare you point out that some statement is stupid'? I ask again: What result of the paper suggests there is a as-of-yet unidentified mechanism of regulation of gene expression? And by the way: Of course we do not expect to find a 'decision mole Ike' and the very notion is indeed absurd. I've never heard of any scientist looking for it either. Have you? hrun0815

Got enough yet? :) Dionisio

The non-catalytic N-terminal domain of ACS7 is involved in the post-translational regulation of this gene doi: 10.1093/jxb/eru211 Post-transcriptional control of the expression of the 1-aminocyclopropane-1-carboxylate synthase (ACS) gene family is important for maintaining appropriate levels of ethylene production. However, the molecular mechanism underlying the post-transcriptional regulation of type 3 ACS proteins remains unclear. Multiple sequence alignment revealed that the N-terminus of type 3 ACSs was longer than that of other ACSs. Fusing the N-terminal 54 residues of ACS7, the sole type 3 ACS in Arabidopsis, to the ?-glucuronidase (GUS) reporter significantly decreased the stability of N7(1–54)–GUS fusion protein. Among these 54 residues, residues 1–14 conferred this negative effect on the GUS fusion gene. Consistently, a truncated form of ACS7 lacking residues 1–14 was more stable than full-length ACS7 when transgenically expressed in Arabidopsis and led to a more severe ethylene response phenotype in the light-grown transgenic seedlings. Interestingly, the ACS7 N-terminus had no effect on the stability of N7–GUS and ACS7 proteins at the etiolated seedling stage. Both exogenous 1-aminocyclopropane-1-carboxylic acid (ACC) treatment and salt stress could rescue the levels of accumulation of N7–GUS fusion protein in light-grown seedlings. These results suggest that the non-catalytic N-terminus of ACS7 is involved in its own post-translational regulation. The proteasome inhibitor MG132 suppressed degradation of full-length ACS7 in vivo, but had little effect on the N-terminal truncated form of ACS7, indicating that the N-terminus mediates the regulation of ACS7 stability through the ubiquitin–26S proteasome pathway. http://jxb.oxfordjournals.org/content/early/2014/05/24/jxb.eru211 Dionisio

Post-translational modifications of intermediate filament proteins: mechanisms and functions doi:10.1038/nrm3753 Intermediate filaments (IFs) are cytoskeletal and nucleoskeletal structures that provide mechanical and stress-coping resilience to cells, contribute to subcellular and tissue-specific biological functions, and facilitate intracellular communication. IFs, including nuclear lamins and those in the cytoplasm (keratins, vimentin, desmin, neurofilaments and glial fibrillary acidic protein, among others), are functionally regulated by post-translational modifications (PTMs). Proteomic advances highlight the enormous complexity and regulatory potential of IF protein PTMs, which include phosphorylation, glycosylation, sumoylation, acetylation and prenylation, with novel modifications becoming increasingly appreciated. Future studies will need to characterize their on–off mechanisms, crosstalk and utility as biomarkers and targets for diseases involving the IF cytoskeleton. http://www.nature.com/nrm/journal/v15/n3/abs/nrm3753.html Dionisio

The growing landscape of lysine acetylation links metabolism and cell signaling doi:10.1038/nrm3841 Lysine acetylation is a conserved protein post-translational modification that links acetyl-coenzyme A metabolism and cellular signalling. Recent advances in the identification and quantification of lysine acetylation by mass spectrometry have increased our understanding of lysine acetylation, implicating it in many biological processes through the regulation of protein interactions, activity and localization. In addition, proteins are frequently modified by other types of acylations, such as formylation, butyrylation, propionylation, succinylation, malonylation, myristoylation, glutarylation and crotonylation. The intricate link between lysine acylation and cellular metabolism has been clarified by the occurrence of several such metabolite-sensitive acylations and their selective removal by sirtuin deacylases. These emerging findings point to new functions for different lysine acylations and deacylating enzymes and also highlight the mechanisms by which acetylation regulates various cellular processes. http://www.nature.com/nrm/journal/v15/n8/abs/nrm3841.html Dionisio

Non-histone protein methylation as a regulator of cellular signalling and function doi:10.1038/nrm3915 Methylation of Lys and Arg residues on non-histone proteins has emerged as a prevalent post-translational modification and as an important regulator of cellular signal transduction mediated by the MAPK, WNT, BMP, Hippo and JAK–STAT signalling pathways. Crosstalk between methylation and other types of post-translational modifications, and between histone and non-histone protein methylation frequently occurs and affects cellular functions such as chromatin remodelling, gene transcription, protein synthesis, signal transduction and DNA repair. With recent advances in proteomic techniques, in particular mass spectrometry, the stage is now set to decode the methylproteome and define its functions in health and disease. http://www.nature.com/nrm/journal/vaop/ncurrent/abs/nrm3915.html Dionisio

Any outstanding questions on the OP? :) Dionisio

Post-translational modifications The diversity of modifications that a nascent peptide acquires as it is transported to its target cellular location is long established, as is the ability of particular tags such as phosphorylation and ubiquitylation to regulate signalling and protein turnover, respectively. But in more recent years we have seen a renaissance of interest in the ability of additional modifications — from ubiquitin-like proteins to moieties such as sugars or methyl, acetyl and prenyl groups — to target specific sites in proteins and to coordinately exert dynamic control over protein function in diverse cell biological contexts. http://www.nature.com/nrm/series/ptm/index.html Dionisio

Post-translational modification of mitochondria as a novel mode of regulation. doi: 10.1016/j.exger.2014.03.006 Mitochondria not only form the metabolic hub, but also are crucial players in many cellular pathways, like apoptosis and innate immune response, putting the organelle in a central position in controlling cellular function and fate. As novel and powerful regulators of mitochondrial processes and hence mitochondrial-controlled pathways, post-translational modifications (PTMs) have emerged in the last years. In this review, we will summarize the current state of knowledge on PTMs occurring in mammalian mitochondria with a focus on phosphorylation, acetylation, succinylation and ubiquitination. We will highlight their regulatory role in metabolism, autophagy and apoptosis as well as communicating element to cellular stress response pathways such as the immune response. Finally, we will discuss open questions in this exciting research area and point out how mitochondrial PTMs might impact age-associated pathologies. http://www.ncbi.nlm.nih.gov/pubmed/24632076 Dionisio

PTHGRN: unraveling post-translational hierarchical gene regulatory networks using PPI, ChIP-seq and gene expression data. Interactions among transcriptional factors (TFs), cofactors and other proteins or enzymes can affect transcriptional regulatory capabilities of eukaryotic organisms. Post-translational modifications (PTMs) cooperate with TFs and epigenetic alterations to constitute a hierarchical complexity in transcriptional gene regulation. While clearly implicated in biological processes, our understanding of these complex regulatory mechanisms is still limited and incomplete. Transcriptional regulation dominated by interactions between transcription factors (TFs) and DNA sequences is a center for control of gene expression in eukaryotic organisms. The ability of TFs to regulate the target genes is largely modified by post-translational modifications (PTMs) among TFs, cofactors and other proteins or enzymes upstream of transcriptional process. The combinational action of PTMs, TFs, as well as epigenetic factors forms a hierarchical “regime” to perform gene regulation. Many biological processes or functions like human disease, cell differentiation and development involve the synergistic coordination of these multi-level regulators. Despite its importance, our understanding of such complex regulatory mechanisms is incomplete. https://globalmedicaldiscovery.com/key-medical-diagnostics-articles/pthgrn-unraveling-post-translational-hierarchical-gene-regulatory-networks-using-ppi-chip-seq-gene-expression-data/ Dionisio

A conserved type IV pilin signal peptide H-domain is critical for the post-translational regulation of flagella-dependent motility DOI: 10.1111/mmi.12673 This novel post-translational regulatory mechanism, which employs components that promote biofilm formation to inhibit motility, can provide a rapid response to changing environmental conditions. A model for this regulatory mechanism, which may also be present in other prokaryotes, is discussed. http://onlinelibrary.wiley.com/doi/10.1111/mmi.12673/abstract Dionisio

Post-transcriptional and post-translational regulation of epithelial transport Although defective epithelial fluid and electrolyte transport can lead to a range of debilitating conditions, including cystic fibrosis, diabetes insipidus, and diarrhoeal diseases, we are only beginning to understand the molecular mechanisms involved. While the gene expression profiles of different epithelial cell populations are important in determining their compliment of transport proteins, it is the post-transcriptional and post-translational regulatory machinery that ultimately dictates their transporting phenotype. This symposium will highlight recent advances in this rapidly evolving field of epithelial physiology by highlighting how post-transcriptional and post-translational regulatory mechanisms dynamically regulate fluid and electrolyte transport in health and disease. http://www.physiology2014.org/scientific-programme/symposia/post-transcriptional-and-post-translational-regulation-epithelial Dionisio

New insights into extracellular and post-translational regulation of TGF-? family signalling pathways doi: 10.1093/jb/mvt046. Members of the transforming growth factor-? (TGF-?) family of secreted proteins are present in all multicellular animals. TGF-? proteins are versatile intercellular signalling molecules that orchestrate cell fate decisions during development and maintain homeostasis in adults. The Smad family of signal transducers implements TGF-? signals in responsive cells. Given the ability of TGF-? ligands to induce dramatic responses in target cells, numerous regulatory mechanisms exist to prevent unintended consequences. Here we review new reports of extracellular and post-translational regulation in Drosophila and vertebrates. Extracellular topics include the regulation of TGF-? signalling range and the coordination between tissue morphogenesis and TGF-? signalling. Post-translational topics include the regulation of TGF-? signal transduction by Gsk3-? phosphorylation of Smads and by cycles of Smad mono- and deubiquitylation. Extension of the ubiquitylation data to the Hippo pathway is also discussed. http://www.ncbi.nlm.nih.gov/pubmed/23698094 Dionisio

#17 bornagain77 Excellent! That's it. Thank you. Dionisio

#16 addendum The ability to self-renew indefinitely and differentiate into all cells of the body makes human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), valuable for research and clinical applications that require specific cell types. Although recent studies have greatly advanced our understanding of cellular pluripotency and its potential utility, it is still unclear how these cells establish, maintain and modulate their pluripotency during cellular reprogramming and differentiation. Recent evidence indicates that the complex signaling networks involved in the regulation of cellular pluripotency are tightly controlled through multiple mechanisms, including post-translational modifications (PTMs). PTMs diversify and extend protein function beyond what is dictated by gene transcripts. They reversibly or irreversibly alter the structure and properties of proteins through biochemical reactions, and a variety of PTMs allow eukaryotic cells to dynamically regulate their signal integration and physiological states. As analytical approaches have improved, the biological influences of many types of PTMs have been identified and are routinely analyzed in many systems. The importance of PTMs is known historically because of their effects on the enzymatic activity of kinases1 and protein degradation. Based on previous and emerging data, it seems evident that PTMs are involved in regulating almost all cellular events, including gene expression, signal transduction, protein-protein interaction, cell-cell interaction, and communication between the intracellular and extracellular environment. Therefore, perturbation of PTMs in cells frequently affects cell physiology as a whole. In addition, the alteration of cellular states (e.g., differentiation of hPSCs or malignant transformation of primary cells) may be accompanied by acquisition of unique PTM hallmarks. http://www.nature.com/cr/journal/v24/n2/full/cr2013151a.html Dionisio

Dionisio, although I don't know what the exact nuances of this particular finding are, of an additional level of regulation for genes/proteins, I do know of a finding for gene/protein regulation that blows neo-Darwinian precepts out of the water. A little known fact, a fact that is very antagonistic to the genetic reductionism model of neo-Darwinism, is that, besides environmental factors, even our thoughts and feelings can 'epigenetically' control the gene expression of our bodies:

Scientists Finally Show How Your Thoughts Can Cause Specific Molecular Changes To Your Genes, - December 10, 2013 Excerpt: “To the best of our knowledge, this is the first paper that shows rapid alterations in gene expression within subjects associated with mindfulness meditation practice,” says study author Richard J. Davidson, founder of the Center for Investigating Healthy Minds and the William James and Vilas Professor of Psychology and Psychiatry at the University of Wisconsin-Madison. “Most interestingly, the changes were observed in genes that are the current targets of anti-inflammatory and analgesic drugs,” says Perla Kaliman, first author of the article and a researcher at the Institute of Biomedical Research of Barcelona, Spain (IIBB-CSIC-IDIBAPS), where the molecular analyses were conducted.,,, the researchers say, there was no difference in the tested genes between the two groups of people at the start of the study. The observed effects were seen only in the meditators following mindfulness practice. In addition, several other DNA-modifying genes showed no differences between groups, suggesting that the mindfulness practice specifically affected certain regulatory pathways. http://www.tunedbody.com/scientists-finally-show-thoughts-can-cause-specific-molecular-changes-genes/ Networks of Genes Respond to Social Experiences - October 13, 2013 Excerpt: It is subjective mind and perception that changes genes, not just external situations. http://jonlieffmd.com/blog/networks-of-genes-respond-to-social-experiences Controlling genes with your thoughts - November 11, 2014 Excerpt: “For the first time, we have been able to tap into human brainwaves, transfer them wirelessly to a gene network and regulate the expression of a gene depending on the type of thought. Being able to control gene expression via the power of thought is a dream that we’ve been chasing for over a decade,” says Fussenegger. http://www.sciencedaily.com/releases/2014/11/141111111317.htm Study shows clear new evidence for mind-body connection - Mindfulness-based cancer recovery - Nov. 3, 2014 Excerpt: A group,, has demonstrated that telomeres – protein complexes at the end of chromosomes – maintain their length in breast cancer survivors who practise meditation or are involved in support groups, while they shorten in a comparison group without any intervention. Although the disease-regulating properties of telomeres aren't fully understood, shortened telomeres are associated with several disease states, as well as cell aging, while longer telomeres are thought to be protective against disease. "We already know that psychosocial interventions like mindfulness meditation will help you feel better mentally, but now for the first time we have evidence that they can also influence key aspects of your biology," http://m.medicalxpress.com/news/2014-11-evidence-mind-body.html

That 'mind' can have a pronounced effect on gene expression is simply completely antithetical to the 'bottom up' reductive materialism upon which neo-Darwinism is based. A view that entails that we are merely victims of our genes with no control whatsoever. Of related note, focused attention of the mind, besides having a pronounced effect on gene expression, is now also shown to have a pronounced effect on 'brain plasticity':

The Case for the Soul - InspiringPhilosophy - (4:03 minute mark, Brain Plasticity including Schwartz's work) - Oct. 2014 - video The Mind is able to modify the brain. Moreover, Idealism explains all anomalous evidence of personality changes due to brain injury, whereas physicalism does not explain mind. https://www.youtube.com/watch?v=oBsI_ay8K70

Quote:

“You don’t have a soul. You are a soul. You have a body.” George MacDonald - Annals of a Quiet Neighborhood - 1892

Verse and Music:

Mark 12:30 Love the Lord your God with all your heart and with all your soul and with all your mind and with all your strength.' CMA Country Christmas 2014 | Michael W. Smith & Carrie Underwood - "All Is Well" https://www.youtube.com/watch?v=cjZfeEJgNRw

bornagain77

Protein post-translational modifications and regulation of pluripotency in human stem cells doi:10.1038/cr.2013.151 Post-translational modifications (PTMs) are known to be essential mechanisms used by eukaryotic cells to diversify their protein functions and dynamically coordinate their signaling networks. Defects in PTMs have been linked to numerous developmental disorders and human diseases, highlighting the importance of PTMs in maintaining normal cellular states. Human pluripotent stem cells (hPSCs), including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), are capable of self-renewal and differentiation into a variety of functional somatic cells; these cells hold a great promise for the advancement of biomedical research and clinical therapy. The mechanisms underlying cellular pluripotency in human cells have been extensively explored in the past decade. In addition to the vast amount of knowledge obtained from the genetic and transcriptional research in hPSCs, there is a rapidly growing interest in the stem cell biology field to examine pluripotency at the protein and PTM level. This review addresses recent progress toward understanding the role of PTMs (glycosylation, phosphorylation, acetylation and methylation) in the regulation of cellular pluripotency. http://www.nature.com/cr/journal/v24/n2/full/cr2013151a.html Dionisio

#13 BA77 Thank you. Dionisio

#12 Box FYI - an important rule in the ethical code of blog discussions is that you should refrain from asking any kind of easy questions that might force your interlocutors to admit they don't know. Violating such basic rule might lead to unfair treatment or humiliation of your interlocutors, which is politically incorrect, hence unacceptable. Now you know for next time. :) Dionisio

Dionisio, I will take a look over it in a bit and see if I have anything in my notes to add bornagain77

hrun0815: These results do not suggest that there is an unidentified mechanism of gene regulation. Translational regulation and protein stability has been described and studied for over 25 years.

And is there any clarity yet? What regulates genes? Sure there has been the identification of a multitude of "influencers" which are in turn influenced and so forth. But where in this web of interactions is a regulator? To put it another way: what has decision power? Are we really expecting to find the "decision-molecule"? Is such a concept even thinkable? Box

News, Please, don't take me wrong, I'm not trying to put at end to the discussion here. Just trying to comment on the interesting OP. :) Dionisio

BA77, Please, give me a hand with this. I don't want to shutdown this discussion. That's not my intention. :) Dionisio

Another related paper: Regulation of autophagy by protein post-translational modification doi:10.1038/labinvest.2014.131 Autophagy is a lysosome-mediated intracellular protein degradation process that involves about 38 autophagy-related genes as well as key signaling pathways that sense cellular metabolic and redox status, and has an important role in quality control of macromolecules and organelles. As with other major cellular pathways, autophagy proteins are subjected to regulatory post-translational modification. Phosphorylation is so far the most intensively studied post-translational modification in the autophagy process, followed by ubiquitination and acetylation. An interesting and new area is also now emerging, which appears to complement these more traditional mechanisms, and includes O-GlcNAcylation and redox regulation at thiol residues. Identification of the full spectrum of post-translational modifications of autophagy proteins, and determination of their impact on autophagy will be crucial for a better understanding of autophagy regulation, its deficits in diseases, and how to exploit this process for disease therapies. http://www.nature.com/labinvest/journal/vaop/ncurrent/full/labinvest2014131a.html Dionisio

Any questions yet? :) Dionisio

Another related paper: Post-translational dual regulation of cytochrome P450 aromatase at the catalytic and protein levels by phosphorylation/dephosphorylation DOI: 10.1111/febs.13021 The post-translational regulation of aromatase has not been well characterized as compared with transcriptional regulation. Several studies of post-translational regulation have focused on decreases in catalytic activity following phosphorylation. We report here dual post-translational regulation of aromatase, at the catalytic activity and protein levels. Microsomal aromatase prepared from JEG-3 cells was rapidly inactivated and subsequently degraded in the presence of a cytosolic fraction with calcium, magnesium, and ATP. In a reconstituted system consisting of microsomal and cytosolic fractions, aromatase was protected from protein degradation by treatment with alkaline phosphatase, whereas degradation was enhanced by treatment with calcineurin inhibitors (FK506 and cyclosporin A). Furthermore, aromatase was protected from degradation by treatment with kinase inhibitors, especially the calcium/calmodulin kinase inhibitors KN62 and KN93. Similarly to the reconstituted system, aromatase in cultured JEG-3 cells was protected from degradation by KN93, whereas FK503 increased degradation in the presence of cycloheximide, although cellular aromatase mRNA levels were unchanged by these reagents. Knockdown of calcineurin and calcium/calmodulin kinase II (CaMKII) with small interfering RNAs resulted in a dose-dependent increase in aromatase degradation and protection from degradation, respectively. The cytosol fraction-dependent phosphorylation of microsomal aromatase was inhibited by calcineurin, KN62, and KN93, and promoted by CaMKII and FK506. These results indicate that aromatase is regulated acutely at the catalytic activity level and subsequently at the enzyme content level by CaMKII/calcineurin-dependent phosphorylation/dephosphorylation. http://onlinelibrary.wiley.com/doi/10.1111/febs.13021/abstract Dionisio

Another related article: Three novel quantitative trait loci for skin thickness in swine identified by linkage and genome-wide association studies DOI: 10.1111/age.12163 Skin is the largest organ in the pig body and plays a key role in protecting the body against pathogens and excessive water loss. Deciphering the genetic basis of swine skin thickness would enrich our knowledge about the skin. To identify the loci for porcine skin thickness, we first performed a genome scan with 194 microsatellite markers in a White Duroc × Erhualian F2 intercross. We identified three genome-wide significant QTL on pig chromosomes (SSC) 4, 7 and 15 using linkage analysis. The most significant QTL was found on SSC7 with a small confidence interval of ~5 cM, explaining 23.9 percent of phenotypic variance. Further, we conducted a genome-wide association study (GWAS) using Illumina PorcineSNP60 Beadchips for the F2 pedigree and a population of Chinese Sutai pigs. We confirmed significant QTL in the F2 pedigree and replicated QTL on SSC15 in Chinese Sutai pigs. A meta-analysis of GWASs on both populations detected a genomic region associated with skin thickness on SSC4. GWAS results were generally consistent with QTL mapping. Identical-by-descent analysis defined QTL on SSC7 in a 683-kb region harboring an interesting candidate gene: HMGA1. On SSC15, the linkage disequilibrium analysis showed a haplotype block of 2.20 Mb that likely harbors the gene responsible for skin thickness. Our findings provide novel insights into the genetic basis of swine skin thickness, which would benefit further understanding of porcine skin function. http://onlinelibrary.wiley.com/doi/10.1111/age.12163/abstract Dionisio

Quick explanation of terminology

Quantitative trait locus http://en.wikipedia.org/wiki/Quantitative_trait_locus Expression quantitative trait loci http://en.wikipedia.org/wiki/Expression_quantitative_trait_loci

Dionisio

Is this the abstract of the original paper?

Impact of regulatory variation from RNA to protein DOI: 10.1126/science.1260793 Alexis Battle1,2,*,‡, Zia Khan3,†,‡, Sidney H. Wang3,‡, Amy Mitrano3, Michael J. Ford4, Jonathan K. Pritchard1,2,5,§, Yoav Gilad3,§ + Author Affiliations 1Department of Genetics, Stanford University, Stanford, CA 94305, USA. 2Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. 3Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. 4MS Bioworks, LLC, 3950 Varsity Drive, Ann Arbor, MI 48108, USA. 5Department of Biology, Stanford University, Stanford, CA 94305, USA. + Author Notes ?* Present address: Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218, USA. ?† Present address: Department of Computer Science, University of Maryland, College Park, MD 20742, USA. ?§Corresponding author. E-mail: pritch@stanford.edu (J.K.P); gilad@uchicago.edu (Y.G.) ?‡ These authors contributed equally to this work. The phenotypic consequences of expression quantitative trait loci (eQTLs) are presumably due to their effects on protein expression levels. Yet, the impact of genetic variation, including eQTLs, on protein levels remains poorly understood. To address this, we mapped genetic variants that are associated with eQTLs, ribosome occupancy (rQTLs), or protein abundance (pQTLs). We found that most QTLs are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, eQTLs tend to have significantly reduced effect sizes on protein levels, suggesting that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we identified a class of cis QTLs that affect protein abundance with little or no effect on mRNA or ribosome levels, suggesting that they may arise from differences in post-translational regulation. Received for publication 3 September 2014. Accepted for publication 9 December 2014. Published Online December 18 2014

Would anyone like to discuss thoroughly what this paper may indicate? Yes, no, maybe? :) Dionisio

WD400, you forget the other whopper in the OP: These results do not suggest that there is an unidentified mechanism of gene regulation. Translational regulation and protein stability has been described and studied for over 25 years. Of course if you rely on science aggregators like Phys.org that are further mangled by 'News' to get your science info... well then you get people like BA77, I guess. hrun0815

"The findings point to a yet-unidentified cellular mechanism that regulates gene expression and suggest studies that rely only on RNA measurements to characterize gene function require further analysis." So finding ANOTHER level of gene regulation complexity on top of what was thought to be 'only RNA' regulating gene expression is evidence for Darwinism because??,, Because?? Well because Darwinism likes extra unexpected, and overlapping, levels of complexity being discovered in cells all the time! :) Regardless of how wd400 may try to spin this, this is NOT good news for Darwinism,,, as a commenter on FB put it: 'So basically in our lifetime we've seen cells go from figurative "blocks", to Multidimensional "tools", to "flip-phones" and now its about to go to an even HIGHER state of complexity...like an "ipod".' bornagain77

UD is really on a roll this week... These differences are unrelated to the RNA world, but they are often cited as evidence that most of the genome is functional. "Not only is most of the genome transcribed, but there are tissue-specific differences in RNA abundance between transcripts". This paper is about between-individual differences in gene expression, but still seems to undercut this argument (which wasn't very good so start with, FWIW). wd400