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#1 Cyto

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Posted 24 August 2004 - 08:59 PM


This Pinned Topic will allow for anyone(!) to ask a question about the huge area of Biological Sciences and members of ImmInst will promptly respond in a timely manner. Even if you think the question is small or dumb STILL ASK - chances are there are plenty of people who would like to know the same thing. This thread will also help to localize questions for easy future access if needed.

#2 123456

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Posted 24 August 2004 - 10:18 PM

Are our personalities based on genetical makeup?
e.g Agressive personalities can be bred into and out of various animals.(Dogs etc.)
[hmm]

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#3 Cyto

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Posted 25 August 2004 - 06:50 AM

Well, yes and no.

The commonly known sex steroid called testosterone is a strong regulator of aggressive behavior (AB) and can be confirmed through castration and testosterone supplementation. Another player in AB seems to be progesterone which acts more of like an enhancer but there needs to be more studies done on this one...the only one I know of is done with tree lizards (Urosaurus ornatus) [1].

Anyway, moving from lizards we find that glucocorticoids are found to increase the aggressive behavior in rats and the odd thing is that it is translation independent. When protein synth inhibitors are applied 2 minutes after a hormone injection the AB will not cease but if glucocorticoids are injected 20 before the inhibitors then ablation of the AB will occur. So, with the insight of prot synth inhibitors not affecting AB at first there is insight as to how this must be genome independent until a point in time when translation is needed to keep the AB effect persisting. [2]

And to add to the above we might find that exposure to such AB inducing hormones/steroids could have lasting, maybe even permanent, effects on the individual exposed to the excess and upregulated expression. Male rats injected with testosterone, stanozolol, nandrolone separately during puberty took up to 15 weeks for normal rat behavior to return but the interesting lasting effect was aggressiveness when hurt (tail pinch) [3]. Quite possibly we have an epigenetic change here where maybe the condensation of AB genes within the chromatin is more relaxed for transcription then in normal cases.

Now there will be other factors in this when we talk about humans since the species can show inhibition in situations due to self constraints or social constraints. Meaning morals, goals, laws, social norms etc. But when we look at conserved actions like the aggressive behavior I do think that we can be predisposed for thresh-holds on when we act and how severe it will be.

As for the rest of the personality I can't give such papers that will help me anymore then the latter but a personal story can help. I was preached to at a very early age and much later into my life and had to go to religious functions here and there but I am not conditioned at all. Now, my household is more critical of an atmosphere for failure and I have been around that as much as the religious preaching - and I am a person who has taken in the critical aspect. With understandings such as this I would have to say that nurture and self analysis can play huge parts in even conditioning environments. You look at what helps you survive and what makes sense and you can thusly accept or deny it, not everyone practices self analysis though.

I'm sorry for the yes and no answer but we do really have to return to the "nature vs nurture" talk and say "both to an extent, one maybe more then the other - we may have to do a case by case basis."

[1]General and Comparative Endocrinology
Volume 136, Issue 2 , April 2004, Pages 282-288

[2]Psychoneuroendocrinology
Volume 29, Issue 5 , June 2004, Pages 618-635

[3]Hormones and Behavior
Volume 46, Issue 2 , August 2004, Pages 193-203

#4

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Posted 25 August 2004 - 12:26 PM

Excellent pinned topic column. Well done Bates and BJ. A strategic evolutionary step for ImmInst.

#5 123456

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Posted 27 August 2004 - 06:29 PM

Another question; Is everyone here just analyzing data from researchers and talking about the DNA involvement in the aging process or we do have some actual people who work in labs and are doing the work? [sfty]

Edited by 123456, 27 August 2004 - 06:47 PM.


#6 Lazarus Long

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Posted 27 August 2004 - 10:09 PM

Bates, who runs this thread, and is one of our moderators is an advanced student of biotechnology, as are a number of other contributors to this forum. There are more than a few official researchers as you would define them, Aubrey de Grey for a singularly important example.

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#7 123456

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Posted 28 August 2004 - 01:59 AM

Do people who are relatively more intelligent than others have more neurons; a better built brain structure?
Basically, having a more efficient ability to analyze, theorize, more memory capacity; more accurate memory; ability to reason well etc., is the result of genetic makeup or other?

Can I eat mangoes or other delecious stuff to get smarter? [pirate]

#8 Cyto

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Posted 28 August 2004 - 07:16 PM

Your question reminded me of the transgenetic Doogie Howser Mice.

NR2B a key switch
Tsien's research proves that the gene he used, called NR2B, is a key switch that controls the brain's ability to associate one event with another. He previously created mice that lacked the gene in a tiny region of the brain and showed that they had impaired learning and memory. Adding new or improved function, however, was a harder task and a more rigorous test of the gene's function.

Taken together, these results could be of major interest to researchers trying to understand and treat human disorders that involve the loss of learning and memory. In particular, the NR2B gene could be a target for drug makers, who could try to design medicines that boost its effects. In the long term the results may promote further discussions on ethical and social issues regarding whether and how genetic technology should be used to modify or enhance mental and cognitive attributes in people. (The corresponding gene exists in humans, but its enhancing effect in humans is not known.)

Developing a drug or gene therapy from Tsien's discovery would take many years of testing in animals and humans, but his results tell researchers that the NR2B gene is a good place to start. According to Jonathan Cohen, professor of psychology, Tsien's work assures scientists that the process NR2B controls is not merely an indirect part of learning and memory. "Now we're able to say that it's not just shadowing another area, it's having an effect on its own," said Cohen. "The ability to get in there and change things at a genetic level gives us a level of specificity that is unsurpassed. And that's really exciting."


Also it reminded me of an article Michael Anissimov posted a while back called Neuron Soma Size in the Left and Right Hippocampus of a Genius which gives some insight into how people like Albert Einstein could of been so fruitful in his math career.

Underlying brain features of a genius are not understood. It is not known if there is a smooth continuum between a genius and the thousands of the brightest minds alive today. The few postmortem studies of brains of remarkable mathematicians or physicists typically emphasized the neocortex. In the present study, the hippocampus of Albert Einstein (AE) was investigated postmortem. The importance of the hippocampus is established for long-term, explicit, implicit, and episodic memory, and establishment of semantic associations. A single microscope slide (Nissl-stained stained in Harvey[Image]s lab not long after AE[Image]s death at age 76 years) was available for the left and right sides. Soma size of pyramidal neurons in coronal sections of AE[Image]s left and right hippocampi were photographed, then digitized and systematically measured on a computer in hippocampal subfields CA1, CA2, CA3, CA4, and subiculum. An atypical left-right asymmetry emerged in AE, with soma size being consistently and significantly larger in the left than in the right side in all homologous subfields except for CA2, whereas in 10 ordinary adults, aged 22 to 84 years, there was minimal and inconsistent soma size asymmetry in direction (left vs right) or extent. However, the soma size variability revealed similarities in both AE and the ordinary adults, particularly in hippocampal subfields CA1 and CA2, bilaterally. The direction of the cell size asymmetry in AE[Image]s hippocampi could simply reflect age-related changes in combination with unusual neuronal connectivity of prenatal or experiential origin. This is difficult to ascertain, and the relationship between the hippocampal status at the time of his death and its role in his genius in his most creative years is a matter for debate.


The problem, obviously, is that we can't experiment on humans so we have to look at other model systems in which will limit the answer I can supply. But with the two above news bits I would say that "yes, people can have a predisposed position for becoming what is known as smart." But there are different ways of being smart too. For this I will borrow what most of my Organic Chem professors refer to as "crystalline" and "fluid" memory. Crystalline memory is associated with people who can take information in and keep it there and recall it with ease but they have a hard time adapting to a change in information and thus may need to change what they learned. Fluid is along the lines of people who can change quickly but it takes them a longer time to learn the information.

So what am I trying to say overall: You need to exercise your brain so neurotrophic factors are passing through the synapse and increasing the diameter of your dendrites and axon buds - otherwise you will be dumb later with all lack of activity (pruning). We can have a genetically "better" brain but it may make other tasks like tying your shoes a challenge (Einstein had this problem). The ability to analyze, theorize, and reason would be more of if you were trained how to question and formulate answers based on results then change if needed...more of a science undergrad and post grad training. So it would depend on what the potential genius wants to do in life, I know some majors don't require reason, critical thinking, and postulation.

As for consuming things to help you get "smarter" I would direct that question at the supplement section of ImmInst.org. The answer I would give you is: Eat logically, take your vitamins and supplements, exercise, and be sure to keep learning.

#9 123456

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Posted 28 August 2004 - 07:40 PM

How about this question; since mitochondria clearly has its own set of DNA, is it included in the 23 chromosomes in an egg or sperm? If not, where does it come from ? [8)]

Edited by 123456, 30 October 2004 - 06:41 PM.


#10 Lazarus Long

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Posted 28 August 2004 - 08:36 PM

How about this question; since mitochondria clearly has its own set of DNA, is it included in the 23 chromosomes in an egg or sperm? If not where does it come from ? [8)]


I'll field this one Ryan.

The short answer is no.

All the mtDNA you possess is from your mother. (as noted later this is now a contentious claim). One reason we are interested in the prenatal treatment of mtDNA as it incorporates itself into meiotic division and then forward through the cellular divergence and tissue specialization for the zygote is that the mother's mtDNA is *rejuvenated* in the process. mtDNA appears to start over again in the infant during the period pre and perhaps even a period of post natal development in some tissues. However the child's mitochondria are all going forward roughly with the same relative zero point by birth but this is an entirely different *starting point* than the mtDNA that initiated fetal growth. Is it one change or a series of changes?

Is the change during the cellular haploidal division that forms the ovum?

Is the change during fetal growth only or combined with a step of the process that forms the egg?

I am not sure we yet possess clear answers to these last questions but please I invite all to share what is known. Mitochondrial DNA comes from the mother exclusively but it is not included in the 23 chromosomes at all really, it is a part of the organelle material of the cytoplasm of the ovum to be precise.

A part of the reason comes from the complex symbiotic relationship of all Eukaryotes with either their mitochondria or chloroplasts that were the result of the symbiotic joining of bacterial DNA into primitive Blue/Green Algae, which made multicellular life possible. (Re: Note #2) A possible genetic payback for the donor species that gave up its independence in nature was the security of a more powerful host to protect and continue its DNA.

This cross species relationship also exists in humans and the mtDNA is the proof. It is a totally separate set of genes and the only mtDNA in the offspring is maternal as it is a part of the ovum. Sperm for example do not have mitochondria (read note #1) and cannot survive for very long as a result. They consume no nourishment and process no waste. Sperm are literally made to die (except the lucky one in a million evolutionary lottery winner :)) )

As a cross over comment to the rest of the folks reading this, about the issue of death as a part of *DNA strategy*, the argument could be better made if you discussed the disposable soma of haploids rather than the entire genome IMO.

Mitochondrial DNA

Mitochondria DNA Clarifies Human Evolution

Mitochondrial DNA and human history

Mitochondrial Eve


Note #1
A recent study offering results that goes against the prevailing theory on the exclusive maternal DNA issue
Mitochondrial DNA recombines

Note #2
Manipulation of sexual mutability is one important factor for progressive adaptation. Again *Individual Genes* Diverge (mutate) and *Groups of Genes* (genomes, gene pools and I suggest even *ecologies) over time converge into species (and specialize for internal cellular adaptation of function as well) consequential to procreative selection combined with environmentally appropriate *fitness.*

This article provides an example of techniques for manipulating the possibility of mtDNA mutagenesis through the recombinant joining of parental mtDNA so the possibility is that such sex selection mutagenesis is a part of Speciation Convergence resulting from generational mating selection of Individual Mutational Divergence. (I am adding this for open discussion here or back in the other threads on abiogenesis)
Combining paternally and maternally inherited mitochondrial DNA for analysis of population structure in mussels

Edited by Lazarus Long, 02 September 2004 - 01:40 PM.


#11

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Posted 29 August 2004 - 04:54 PM

LL, 123456 take note: Sperm have mitochondria.

It is only once a sperm fuses with an oocyte that the sperm mitochondria are ubiquinated (targeted for proteolysis). Recent studies suggest that some sperm mitochondria manage to escape and recombine with oocyte mitochondria.


http://www.sciencene...000101/fob3.asp
http://www.biolrepro...tract/55/6/1195
http://www.the-scien...ook_991206.html

#12 Lazarus Long

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Posted 29 August 2004 - 06:31 PM

Yes Prometheus [thumb]

I recant my more outdated statement made earlier and that is why I included reference to the recombinant characteristics of mtDNA too. Thank you for pointing that out and I add that this is a potentially undeveloped method of in-vitro recombination for mammalian genomic material that is not fully *fleshed out* yet.

We have a potentially even easier time manipulating mtDNA than human because of its great simplicity by comparison. This limits the options of what can be done somewhat, but magnifies the impact of the alterations. Because Mitochondria are very much like bacteria already and we understand the manipulation of the bacterial genome much better than the complex higher orders the methodologies for manipulating the genome are already much better established.

BTW, this methodology requires extensive safeguards and controls to prevent spontaneous undesirable disease mutation that could be pandemic. That is one of many reasons there are legitimate risks that must be considered while trying to develop these benefits.

I suggest that direct intentional mutation of mtDNA into better gene & waste *recyclers* that can be externally and intentionally *reset* to *natal* condition may be possible. Instead of targeting the *Human Genome* directly for modification, targeting the Human mtDNA (would that be defined as hmtDNA?) for improving its function and incorporating the characteristics into the body through a vector that gets the mutation into all the cells simultaneously. The mutation then, like a *plasmid*, assimilates itself into the natural cell replacement process, replacing less competitive cells through attrition and *Natural Selection.* Perhaps if a viral or bacterial agent is used it is then processed out through the immune system, while strengthening it too.

The article I offered above on recombinant mtDNA issues offers these statements of conjecture.

ibid: Mussel mtDNA article
Khrapko acknowledged that recombinants were found only in muscle, and that the work provided no evidence of inheritability of recombinants.

Still, said Awadalla, at some point the recombinants will have passed through the germline. “Well, it must have come from somewhere, and if [the authors] have demonstrated that this individual has these two copies [of mitochondrial DNA sequence] and its recombinants, then one of the original paternal copies came from the paternal lineage.”

“One possibility is that a small amount of defective paternal DNA, that was introduced during fertilization, got selective advantage in the muscle due to this detrimental mutation and/or paternal-specific polymorphisms,” Khrapko said.

Eyre-Walker offered another theory: “One aspect of this may be that a little bit of paternal leakage actually is generating a slightly higher mutation rate, so it's possible that a proportion of the mutations we see in mitochondrial DNA are actually generated from these paternal leakage events—which would be intriguing.”



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Posted 30 August 2004 - 04:55 AM

Bates, regarding your post about intelligence, are there drugs which mimic the effect of the gene NR2B in the brain without gene therapy. I've never heard of this study until now and am curious about whether such a drug exists or is in production.

The article you linked to is nearly 5 years old so I assume some progress has been made in this area since then.

#14 Cyto

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Posted 30 August 2004 - 01:04 PM

Lol, yes 5 years old can leave quite a big question mark for something so intriguing.

I did have the same question but decided not to post but I do own several, year 2004, journal .pdf 's on current elucidations of the NR2B NMDA receptor. PM me :)).

But I have not found any pharm .pdf 's on a stable agonist analog. Sorry.

* The effect of NMDA-NR2B receptor subunit over-expression on olfactory memory task performance in the mouse

Abstract
The N-methyl--aspartate (NMDA) receptor in the forebrain is thought to modulate some forms of memory formation, with the NR2B subunit being particularly relevant to this process. Relative to wild-type mice, transgenic animals in which the NR2B subunit was over-expressed demonstrate superior memory in a number of behavioral tasks, including object recognition [Nature 401 (1999) 63]. The purpose of the present study was to explore the generality of such phenomena, interpreted as the effect of increasing NR2B expression on the retention of other types of sensory-related information. To accomplish this, we focused our evaluation on the highly salient sensory modality of olfaction. In the first experiment, mice performed both a novel-object-recognition task identical to that performed by Tang et al. [Nature 401 (1999) 63] and a novel-odor-recognition task analogously constructed. Although the results of the object recognition task were consistent with the previous literature, there was no evidence of an effect of NR2B over-expression on the retention of odor recognition memory in the specific task performed. As it was possible that, unlike object recognition memory, novel odor recognition is not NMDA-receptor-dependent, a second task was designed using the social transmission of food preference paradigm. In contrast to the foregoing olfactory task, there is evidence that the latter procedure is, indeed, NMDA-dependent. The results of the second study demonstrated that transgenic mice with NR2B over-expression had a clear memory advantage in this alternative odor memory paradigm. Taken together, these results suggest the NR2B subunit is an important component in some but not all forms of olfactory memory organization. Moreover, for those functions that are NMDA-receptor-dependent, these data support the growing literature demonstrating the importance of the NR2B subunit.


* Antiparkinsonian activity of Ro 25-6981, a NR2B subunit specific NMDA receptor antagonist, in animal models of Parkinson's disease

Abstract
(NMDA) receptor antagonists have antiakinetic and antidyskinetic effects in animals models of Parkinson's disease (PD). However, non-selective inhibition of NMDA receptors throughout the central nervous system may result in undesired effects such as ataxia and psychosis. We therefore studied Ro 25-6981, an activity-dependent antagonist of NMDA receptors containing the NR2B subunit which are predominantly expressed in the striatum. Ro 25-6981 induced contraversive rotations in 6-hydroxydopamine (6-OHDA)-lesioned rats without stimulating locomotion in normal rats and reversed parkinsonian symptoms in 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP)-treated common marmosets. Due to the small number of marmosets, there were no significant differences between Ro 25-6981 and vehicle though there was a significant trend toward differences, as shown by the Page test. Furthermore, Ro 25-6981 potentiated the action of levodopa in both species and attenuated the maximal levodopa response in 6-OHDA-lesioned rats chronically treated with levodopa without reducing the overall response. Ro 25-6981 also potentiated the action of the dopamine receptor agonists apomorphine, A68930 and quinpirole in 6-OHDA-lesioned rats. The present observations suggest a therapeutic potential of NR2B-selective NMDA receptor antagonists in the management of PD.


* Alternate splice variants of mouse NR2B gene

Abstract
Two alternate spliced transcripts of N-methyl--aspartate receptor (NR2B) gene derived from a common promoter have been reported earlier. In the present study, we have examined the expression of alternative splice variants of NR2B gene using 5¡ä rapid amplification of C terminal end (RACE) in the RNA derived from mouse cortex. RT-PCR was performed to confirm the RACE data. Here we report the occurrence of three transcripts containing a novel alternate spliced exon, we refer to as exon 1¡ä. This new exon is located upstream of the transcription start site identified by Klein et al. [Gene 208 (1998) 259] in the 5¡ä untranslated region (UTR) of NR2B, thus making a new alternate 5¡ä end of the NR2B transcript. The molecular nature of the transcripts containing the new exon appears to be highly heterogeneous. These results are interesting in that they are of potential importance in translational regulation of the NR2B gene.


* Changes in the expression of the NR2B subunit during aging in macaque monkeys

Abstract
Humans, non-human primates and rodents show declines in spatial memory abilities with increased age. Some of these declines in mice are related to changes in the expression of the epsilon2 (2) (NR2B) subunit of the N-methyl--aspartate receptor. The purpose of this study was to determine whether primates show changes during aging in the mRNA expression of the NR2B subunit. In situ hybridization was performed on tissue sections from three different ages of Rhesus monkeys (Macaca mulatta; 6¨C8, 10¨C12, and 24¨C26 years). There was a significant decrease in the mRNA expression of the NR2B subunit overall in the prefrontal cortex and in the caudate nucleus between young and old monkeys. There were no significant changes in NR2B mRNA expression in the hippocampus or the parahippocampal gyrus. The results in the prefrontal cortex, caudate and hippocampus were similar to those seen previously in C57BL/6 mice during aging, which suggests that mice may be useful as a model for primates to further examine the age-related changes in the expression of the NR2B subunit of the NMDA receptor in several important regions of the brain.


* Activation of NR1a/NR2B receptors by soluble factors from APP-stimulated monocyte-derived macrophages: implications for the pathogenesis of Alzheimer¡¯s disease

Abstract
Amyloid- peptide (A), the major component of amyloid plaques, can activate brain mononuclear phagocytes (MP; macrophages and microglia), leading to their secretion of neurotoxins. Recent studies strongly suggest that MP-mediated neurotoxicity plays an important role in the pathogenesis of Alzheimer¡¯s disease (AD). To further explore this notion, human monocyte-derived macrophages (MDM) were stimulated with naturally secreted -processing soluble amyloid precursor protein/p3 (APPs/p3) or -processing APP/A (APPs/A). MDM conditioned media (MCM) was recovered and tested for its ability to activate recombinant N-methyl--aspartate (NMDA) receptor subtype NR1a/NR2B expressed in Xenopus oocytes. Pressure ejection of APPs/p3- and APPs/A-stimulated MCM produced inward currents of 59.5¡À8.9 nA (mean¡ÀS.E.M., n=31) and 111.1¡À21.0 nA (n=42) in NR1a/NR2B-expressing oocytes, respectively. The MCM-induced currents were concentration dependent and blocked by 50 M of the NMDA receptor antagonist 2-amino-5-phosphnovalerate, but not by a non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 M). The APPs/p3- and APPs/A-stimulated MCM placed in non-injected oocytes failed to generate inward current. These results demonstrate that APPs/A-stimulated MCM directly activate NMDA receptor subtypes relevant in the pathogenesis of AD.



#15 xanthine

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Posted 19 October 2004 - 07:55 PM

Hrm, bored at lunch, scrolling through some betterhumans stuff.

Found this: http://betterhumans....ID=2004-09-30-1

Social Impacts aside, would the effects of such vaccinations [if properly maintained as mentioned] be passed on to offspring genetically?

The same goes for other vaccinations.. Like smallpox, or polio..

#16 Cyto

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Posted 19 October 2004 - 10:19 PM

Mainly no, but I'll do a "what if"

B Memory cells, as in their name, can carry the ability to detect and deploy IgG's faster while the rest it still pervading the body (they have higher affinity for the antigens of X pathogen).

But B memory cells hide in the bone marrow. But infants do receive antibodies (via mom's milk) which can get them a "passive immunity" which doesn't last. And specified B Cell do not, as far as a know, translocate genetic material of the high affinity for X pathogen to gametes.

But if the infant were to have the flu while still nursing and the mother has flu antibodies presents at the glands, there can be a better chance for the kid to confer resistance faster. Its not what your asking exactly, but I had to do it.
-------------------------------------------------------

If I didn't answer your question please to PM me or just post the message here but, and here is the funny part, I currently have the stomach flu for the past 5 days and I'm really angry about the flu vac. ordeal. But I apologize if you need to reiterate a few things.

#17 123456

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Posted 30 October 2004 - 04:46 AM

1. What is the genetic difference from an "Adult Stem Cell" in contrast to "Embryotic Stem Cell", if there is any?

2.Maybe we can get everything needed from adult stem cells rather than concentrating so much effort towards Embryotic Stem Cells. Think of it, if your answer is just that the Embryotic Stem Cell has more ability than Adult Stem Cells because it has more parts activated (Less restrictions placed on the DNA by the protein or proteins that shuts it off), then both are essentially the same stuff, Right?

Why not have chronological DNA mapping?; Periodic Blood samples, Hair samples, fingernail samples etc. taken from individuals from when they are an infant throughout their life to see which, if any of the Genes, is turned on or off. We lose our baby tooth and grow adult teeth, we go through puberty(Chest Hair, Voice Changes) and such, it is at these times we may be able to see the parts of the DNA being Switched On or off.

You biotech guys, correct me in anything I have said wrong.


Edit: Spelling.

Edited by 123456, 30 September 2006 - 02:34 PM.


#18 Cyto

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Posted 30 October 2004 - 07:33 AM

Think of it, if your answer is just that the Embryotic Stem Cell has more ability than Adult Stem Cells because it has more parts activated (Less restrictions placed on the DNA by the protein or proteins that shuts it off), then both are essentially the same stuff, Right?


Well differentiated cells can have a harder time flying back in retrograde due to characteristic gene arrays that induce a specific cell type (ie: mesenchymal stem cells). Cellular memory modulation via methylation, silencing factors etc are in place to make reverting harder - to remove them and activate desired transcripts has taken ASC research a while and still continues on today. An interesting article I have run by talks about the propensity for neural stem cells to form vascular tissue when cultured (w/ endo cells), which makes sense since neural tissues usually need high vascularization. So this doesn't layout that its easy to alter a cells into anything but rather there seems to be an ability for specific cell types to phase into other cell types that relate in a necessary way to the dominant tissue. Nature Reviews Molecular Cell Biology 5, 678 (2004); doi:10.1038/nrm1474

When you characterize ESCs you can detect the Oct-4 gene (transcription factor) which is produced by undifferentiated cells. You can allow ESCs to spontaneously differentiate into random cell types or you can guide it via growth factors without having to worry about prior epigenetic determination. ESCs can also be more immuno-friendly and don't have the problem, as bad as, ASCs in cell hybrid formation - being that cells can merge with one another and so this wouldn't be that productive in regenerative medicine (being able to identify this problem and possibly fix it is getting better and better though, the article above is a good example for this). Now I'm not going to make a case that ESCs are "better" than ASCs since they both add to understanding of controlling cellular fates, retrograde and anterograde.

And we are not concentrating so much on ESCs, its actually quite the other way around. Since the limits of ESC funding in the US is stunted compared to that of Adult Stem Cell Research there is more investigation in the latter area.

Chrono DNA mapping is too long for a research project, you can't map all the cellular memory module shifts and to pinpoint and characterize all the transcription factors flying around at the time is quite a long task. Researchers have been reporting on the effects of specific transcription factors for quite some time and this helps when you are trying to dictate a cellular role. We can take gene expression profiles of cells to see if they are what they are at the molecular level (cardio cells I would expect to see a high expression of actin and its folding factors prefoldin/TRiC thereof). And even if we did know the whole story via some imaginary new-fast-epigenetic mapping tech we would still have a long road ahead, like we do now, when it comes to dog-walking it back to a very "primitive state." This goes back to the transcription factor research, it seem more cost and time effective to research the cause and effect of a high-impact factor rather than try and ID tons of proteins attached to X base pairs which would take mass expression of each one and running it through something like a mass- spec. And since our methods would require destruction of the cells we would, if we used a epi-mapper, have a protein presence readout but still have to investigate which prots are the main effectors. So, I think that the course of action where we look for high expression of X factor during a specific cell type and use that as the morphogenic inducer for others is a way that we would have to go either way.

Extra:

DNA demethylation is necessary for the epigenetic reprogramming of somatic cell nuclei

Dual regulation of Snail by GSK-3-mediated phosphorylation in control of epithelial–mesenchymal transition

Edited by Bates, 30 October 2004 - 10:37 PM.


#19 123456

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Posted 30 October 2004 - 06:19 PM

Thanks for taking the time to explain these bitotech stuff to me Bates along with the other guys who are in this field; I appreciate, and always will appreciate it. The very least I can do is give moral support to you guys who are actually doing something about aging. With good people like yourselves, hopefully biological immortality can be achieved in my lifetime. [ii] [thumb]

#20 lightowl

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Posted 31 October 2004 - 06:09 PM

I have heard that stem-cells are immortal and can divide endlessly, is that true?

If that is true, would it then be possible to assemble one single stem cell of any kind, including embryonic, from basic building blocks ( atoms and/or standard molecules ) and then "auto replicate" as many designer cells as needed?

I guess the ethical question would still be there. Are these cells considered human life even when constructed totally from scratch in a lab? - You don't have to answer that :p

I am assuming that in our not so distant nanofuture we will have such capabilities. Maybe not perfect control, but a good step towards it. Self assembly and replication will be a powerful tool in our nanoworld.

Thanks for this excellent topic.

#21 Cyto

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Posted 01 November 2004 - 02:36 AM

Well you can immortalize cells. A major way is by using the viral prot called Large T Antigen, but these cells are cancerous and would need to be kept in vitro.

I think your talking about if I were to continuously culture stem cells in a dish? In that case you could, that is how standard lines are made today, but I don't think its in our best interest to keep pushing the population doublings to see how far we can go. A major factor you could use is Nanog and a detectable signal prot could be the Oct-4 protein, both of these are associated with an undifferentiated ESC. As for in the body we obviously have external factors that would keep stem cells in general from actually pulling off their full potential of doublings. Chemical and radiation damage along with the possible mistake in replication can steer the cells into a curb at some point in their lifespans.

So, yea, we could run it supposedly for a long time but the problem with trying to run a culture line is that the external factors that can cause problems. Cultured stem cells don't have the protection of deep tissues like in vivo SCs do.

Im not being a doom-sayer about this though, culture lines are very nice when everything goes well. And "in the body cells" are nice when everything goes well. [lol]

#22 Lazarus

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Posted 06 November 2004 - 07:24 AM

of the three, whihc do you think would be the best school to go to for Biomolecular Enginering

GA Tech
MIT
Cal Tech

???

#23 Cyto

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Posted 06 November 2004 - 08:56 AM

AH! Good to see you Lazarus!

Good question too.

First though, I don't know if you mean grad school or undergrad, so I assume the undergrad (shrug).

Now Caltech has an undergraduate course plan for Chemical Engineering and this means that you will take 3 years of normal chem engineering classes but on the fourth you then get to diversify into particular sections, which in this case you would go with the Biomolecular part. (Bottom of first page) So its not too bad.


Now the MIT has a Nice spread of grad concentrations (Here) but when you go to the undergraduate section you will see that the degree you can get is a Biomedical Engineering minor.

The BME minor is open to all undergraduate majors at MIT, but is best when combined with a science or engineering major. Some departments are also developing tracks that emphasize the interface of engineering with biology or medicine.

Why only a minor?

So you would need to tie it to a bio degree major or something science-like. You may not want to do this.

But supposedly this will happen:

The Biological Engineering Division is submitting a proposal for a new BE SB degree to the Institute in the 2004-2005 AY. The curriculum for the new SB comprises nine new core subjects that define Biological Engineering as a discipline at the undergraduate level. Our goal is for the proposal to be officially approved by the end of Spring 2005; this would enable students who enter MIT in Fall 2005 to major in BE.


Don't know either if you would like to be a "test" group for when this comes out.


GA Tech has a powerpoint slide show, and that was fun to flip through (Click on the Undergrad program). Here is a list of reqs for the Biomolecular Engineering (Its a pdf Here you also have the choice of combining a BS/MS degree (5 year course, start working on MS in the 4th year while finishing the BS and the 5th year you get a MS) interesting option.

Established in 1901, Georgia Tech's School of Chemical & Biomolecular Engineering has a distinguished history of educating students who become leaders in industrial organizations and universities. Today, the School enrolls more than 800 students, and graduated 147 students from summer 2001 through spring 2002, awarding 126 bachelor's degrees, 6 master's degrees, and 15 doctoral degrees.


In the list of reqs I find that you get a core of biochem I&II which in Caltech only does intro to biochem the fourth year...and if your going to be altering, say, the huge topic of proteins (!) you need to understand the business end of prots which is to catalyze (rates in which). You also do take a kinetics course here, that will help to drive home good points like the Michaelis-Menten Kinetics equations etc...

Overall I like the GA Tech with its classes and they just sound a lot easier to work with, which is great for such a busy subject.


Tell me if that didn't help and we can go from there.

Edited by Bates, 06 November 2004 - 07:33 PM.


#24 Karomesis

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Posted 09 April 2005 - 07:56 PM

how soon before we develop a bioinformatically correct simulation of the cell? Do you believe moores law will be the driving factor behind its inception?

Is protein folding the "holy grail" of biology as some say it is?

#25 Cyto

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Posted 10 April 2005 - 02:13 AM

Mmmmm, maybe someone other than I would be better at answering this...or more optimistic.

A 'bioinfo-correct sim of a cell' I wouldn't count on soon or in a while. The computing power would of course help but we still don't know all we need to build the cell for which the speed could aid. Not that we know little about cells but we would need to pool all of it together in some code, algorithms developed to mimic the unique individual functions (blanket statement for how each biomolecule interfaces with eachother, Ill touch on it in the next post).
But then again my opinion is an opinion.

Now, as for folding let me put that on a separate post. But I'm more in the positive light of this area, even if full prediction I dont see 'comming of age' by the time we would need it.

#26 Cyto

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Posted 10 April 2005 - 03:03 AM

So I recall that you’re a computer person so I assume your talking about computational prediction of folding? Or looking for the "optimal solution."

The problem with looking for an optimal solution for a final fold in a protein is that the genetic algorithms (GAs) used can't guarantee a final solution since it hasn't explored all the possible "optimal solutions" in the free energy (FE) landscape (since this is based off the decline in Gibbs’s Free Energy). Keep in mind also that is only for tertiary structures, not the fully formed quaternary structure (if applicable). So they are making GAs that search only in "promising shallows" of the FE landscape which can be misleading due to some proteins folding FE's (hitting peaks before the shallows) getting worse before they get better. And post-translational mods, (ie) being N-Glycation at an Asn-X-Thre/Ser sequence is not always a guarantee at each sequence due to structural transfer blocks etc. So while it may be probable, it isn't certain. Another problem that others are trying to get past is all the van der wals forces (and other charge/non-charge associations) as a whole by studying larger protein domains and how they move in reality. One group is looking at the arm of the GroEL (e. coli) and how it moves (A new way to learn how large proteins move) But GroEL sucks compared to the even more pleiotropic TRiC chaperonin we have [wis].

While pharma is going to pee its pants about not having unbridled control over the formation the real world of folding is still neat. And yes, I do say computing power can only help with this. The idea of being able to predict all that will happen to a protein of interest (p.o.i.) is great but the GAs still need work. I would rather devote time to finding out if I could enhance ER associated degradation (and exceptions thereof), glucoslytransferases detection of free energy, stress transducers upregulative capabilities etc. Being that I think this avenue is better for the movement, personally. (no, I don't think its the holy grail)

There is an interesting bit I have read about a couple months ago about natively unstructured domains on proteins. It seems that as we go up the evolutionary ladder, if you follow such things, you find that proteins get more and more of what is referred to as "disordered domains" that will fold, with low sequence complexity, once about to bind to the target domain. Most of these are DNA-binding proteins like p53, kinases, ribosomal interacting proteins (I think that was the third one) - but they will have hydrophobic regions that actually form the ordered structure (has hydrophobic stretches leading to high sequence complexity) then the other, unstructured will have high polar sequence residues.

So, the "protein quartet" (I think is more inclusive than the trinity) being [random coil -> pre-molten globular -> molten globular -> ordered] this disordered region protein would be considered molten globular.
Which would be that it stays in a state of disorder up until the moment of contact in which the random coil will occur. Pretty neat.

Now this goes on to how we can actually be buffering our genetic variability and allows us to take on greater amounts of mutations without complete dissonance. Since the contact areas are not as specific at would be an enzyme rxn there is room for change in the intermediary residues, even if the intermediary residues are to change it could possibly be that other mutations that occurred could supplement for the change due to these domains having loose conformation. This is even seen in the molecular chaperones, which bind to hydrophobic stretches on nascent proteins - in which the MCs do express protein client selectivity so there has to be a "limit" to how much the disordered domains can alter for binding

Edited by Bates, 14 May 2005 - 02:24 AM.


#27 John Schloendorn

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Posted 10 April 2005 - 03:32 AM

The main problem I see with cell simulation is the use of multiple feedback loops that can amplify minuscule inaccuracies in the underlying physical law. The equations we have to predict atomic orbital interactions (chemical bonding) are approximations that are only good for small systems with little error-amplification. So we'd have to discover much better physical law first. Could happen, though. If anything like occams razor holds, the "true" algorithms might not even need that much computer power. But if you want to live to see these times, I'd strongly recommend doing some stem cell research in the meantime...

#28 Karomesis

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Posted 10 April 2005 - 03:39 AM

bates, did you stat at a holiday inn express last night? [lol] I am taking it , that you beleive in a basic sense , that with our current mode of computation; processing the data for folding is too comprehensive? Do you think quantum computing would make haste on our dillemas? You spoke, in the beggining, of a time pressed scenario: " I don't see coming of age by the time we would need it". correct me if I am taking this the wrong way, but it seems to me that you are either

A. invisioning an extremely slow progression of moores law [glasses]


B. a chronologically advanced peer who sees the glass as half empty [huh]


thanks for the answer, I hope I can talk to you someday soon as a coleague, rather that a layman.



John schloendorn, Already working on it [thumb] At least in the political sense. It is extremely unfoutunate that I cannot offer more assistance in the area of biology. [cry]

#29 Cyto

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Posted 10 April 2005 - 03:50 AM

"A. invisioning an extremely slow progression of moores law chasses.


B. a chronologically advanced peer who sees the glass as half empty."

Na, I don't see computational time being slow - and I may see the glass half full in a bad way. I understand that doing in silico would be cheaper for pharma and others. But right now I just don't see it helping me find improvements in what area I persue...heck I could just be a bitter old man about this (even though im not old). Overall don't let me rain on folding prediction for you.



I am going to the Protein Stability Conference this summer (july 13-17) and they will be talking about comp folding (i think they will give a while to it) and I am going to try my hardest to record the conference...but they say that I can't.

So I bought a recorder that can do high quality for 10 hours, so I should be able to cut a hole in my pants and then tape it in place or something... but I will post what I can get. It should prove to be neat though, I admit that I am not going for that section but rather engineering thermostability parts and aggregation parts. Course I didnt pay all that to just go and play "note-taker" I'm going to get the voice one way or another (sinister grin). Overall Ill be sure to send ya the stuff after I dice it all up into sections.

To book this BIOSCIENCE ad spot and support Longecity (this will replace the google ad above) - click HERE.

#30 Karomesis

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Posted 10 April 2005 - 04:04 AM

that's awesome. I am looking forward to it. [lol] Are you going to attend Imminst 05 in nov? I am going to attend both SENS in sept 05 and imminst. I'd love to go to all of them but I have to make and sell lights. but all work and no play makes karomesis a dull boy [:o]




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