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How to calculate the number of folds present in a protein
Suppose I have number of PDB files of proteins. How can I get the number of folds present in these proteins? Is the fold count derivable from the PDB files? If so, how?

How do you calculate a fold? Amino acid residues in a protein in vivo always have some angle between them - the carbon backbone is never in a straight line. I'm afraid this question is far too broad.

Do you mean 'fold' as in the topology? So alpha-beta-barrel, sandwich, key-barrel, etc?

@gilleain yes exactly...

There are various ways that you could do this.

CATH is a hierarchical classification system
SCOP is another such system with a different hierarchy
PTGL is the protein topology graph library
Tops motif will scan PDB files and match patterns against it

How you actually apply these tools or lookup within these systems is documented on their websites. However, it depends on what you want to do - look up published structures, or new experimental data.
I should point out that writing software from scratch to determine the fold of a protein may be tricky.

this is what i wanted to know... writing from scratch would be difficult....


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Name of this flower?
i'd like to know the name of this flower.

where is this flower located? try to give us as much information as possible - will make it easier for someone to help you out.

It's a Dutchman's Pipe (aka Calico Flower); the genus has over 500 species, but I'm pretty sure this is it.

source: Stack Exchange

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sort: votes


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This Sequence Data (DNA) has very few Methionin-starts. How is that possible?
I'm working on my first sequencing related project and I'm trying to find proteins with a specific PFAM ID (PF11999). The project is called "MMETSP", I searched the annotations for that ID, identified signal peptides using SignalP and their target locations with a tool called MultiLoc2 (I was looking for extracellular targets only).
Out of the very few sequences that where left after all this filtering, none of the DNA-bits started with the basepair-code "ATG", for Methionine. How can this be?
I used the shell to calculate that only 1,83% of all the sequences start with ATG.
Any ideas on this?

Exactly what sequences are you searching?

I'm looking for Antifreeze proteins (PF11999) in marine diatoms, that are located in the extracellular region. Using the cleavage site provided by SignalP I can isolate the targeting peptide.
However, these peptides seem to have no "start"-code.
I got the sequences by looking up the protein IDs in the fasta files that I got from the annotation-search.

You're just looking at the cleaved peptide sequence then? There's no reason those need to start with a methionine unless they're type-I and don't receive further N-terminal processing.

Well, I'm looking at the DNA coding the peptide. The peptide is located in front of the "maternal" protein, so the ORF should start with a methionine, shouldn't it?

If there are no UTRs in this species and the CDS is annotated as full length then yes. Otherwise no.

Then it should be yes.. I'll talk to my Supervisor monday. Thanks for your time!

If anyone stumbles across this question, I found out what the problem was in the end:
contrarily to my assumption that the DNA sequences where all in proper 5'3'-direction, it turned out that we found the exact ORF on the complementary strand in the other direction and who knows where else. Luckily, the MMETSP-Data also featured a /pep directory, in which the needed sequences where found in a clean version.
Thanks for reading and good Luck.

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Lampreys and the origin of certain brain structures
I'm not sure why, but I'd been under the impression that things like the optic tectum and basal ganglia developed post-2R (the double duplication of the genome ~1/2 Ga).
Lampreys (as far as I'm aware), also have these brain structures. The problem is that TimeTree seems to indicate that - unless the outlier of Otsuka et al is correct - lampreys diverged before then:

While trying to figure out which bit of my thinking is wrong, I came across this article that suggests lampreys had whole genome duplications, but completely separately to those in our lineage.
Does this mean that their structures evolved convergently? (Perhaps they're "obvious" things to evolve post-WGDs?) Or is my initial assumption wrong, and the structures are much older than 2R and pre-divergence from lampreys?
Or something else entirely? I'm confused, and I'm sure I'm missing something: I just don't know what.


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Metazoan branching: Placozoa or Porifera?
Of Placozoa and Porifera, which branched off first? (Conversely: which are closer cousins to us?)
I've heard both suggested as our most distant cousins with bodies, so was wondering which ordering is currently considered most likely. Of suggestions that Placozoa branched off later, I've heard some saying that the branching was even post-Cnidaria/Ctenophora. This seems very unlikely: is it?

Currently we don't even know which of the Porifera or Ctenophora branched off first. However, between the Porifera and the Placozoa, the Placozoa are more similar to Cnidaria + Bilateria.

@entonio Does this resolve the Ctenophora v. Porifera debate? (It does for me, but I don't know if that's because of my bias towards Porifera - like many, I've been very uncomfortable with the analyses that put Ctenophora as the most distant)

Bertie, thanks for the paper, it echoes a lot of what I think about this myself - many recent phylogenetic 'upheavals' are in fact methodologically unsound, and this is probably one of them. Still, my issue is with the whole 'this settles it' discourse - I just don't see that the data is enough to settle some things, but people are eager to have the last word on them. I think one day these times will be looked upon with some condescension, we got a lot of new toys to do phylogeny with, but so far we've been sloppy and dishonest using them.


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Which extinction event killed the highest proportion of organisms?
The P-T extinction (a.k.a. the Great Dying) tends to be considered the worst - for example, Wikipedia states:

It is the Earth's most severe known extinction event, with up to 96% of all marine species and 70% of terrestrial vertebrate species becoming extinct. It is the only known mass extinction of insects. Some 57% of all families and 83% of all genera became extinct. Because so much biodiversity was lost, the recovery of life on Earth took significantly longer than after any other extinction event, possibly up to 10 million years.

Presumably the "96% of all marine species" (which references two books, neither of which I have) is in terms of multicellular marine species or some similar subcategory that's easier to observe in the fossil record (I could be wrong).
My question is this: Would the Great Oxygenation Event not have killed a higher proportion of organisms (taking into account all organisms)?
I know that we don't have any records that can tell us how many died in the GOE and hence this question is necessarily speculative, but surely nearly all organisms pre-GOE would have been obligate anaerobes (and therefore found oxygen to be toxic)?
What I'm unsure about is how single-celled organisms fared in more recent (Phanerozoic) extinctions, as most discussion seems to be in terms of opisthokonts (i.e. animals + fungi) and archaeplastidans (i.e. plants + algae).

Would the GOE have actually killed organisms?  Seems to me that it was slow enough so that oxygen-favoring organisms just reproduced better.

I guess the nuclear war that happened in 2077 doesn't count?

@2077: No, because that just killed off a lot of humans, allowing the biosphere to recover from the Anthropocene Extinction Event.

Do you actually mean "proportion of organisms", or "proportion of species including single-celled organisms"? Your title says the former but your text suggests you mean the latter.

I'm voting to close this question as off-topic because this is SE Biology, not The Guiness Book of Records.

This is a great question. I decided to research it and here is what I found. For some reason the GOE is not on lists of the "big 5" mass extinctions. The question is why?
I think it's due to the pace of the event. The event is described as happening 2.45–2.32 billion years ago.

This is a timescale in billions of years. So it isn't really a proper mass extinction. Little is known about the time scale of the evolution of cyanobacterial lineages.

The GOE is not in the Big Five because the Big Five were recognized based on Sepkoski's work on marine invertebrates from the Phanerozoic (i. e. the last half billion years). The "Big Five" refers only to the main five extinctions of the Phanerozoic.

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What came first? The DNA or the DNA polymerases?
I know this sounds a lot like chicken and egg question and while the latter has an answer, I am intrigued about the former.
A modified form of the question would be, in the course of abiogenesis, what formed first? The DNA or the proteins (hence enzymes and DNA polymerases)?
The principle behind it is that the DNA needs an enzyme to replicate.(DNA pol)
But DNA pol itself, being a protein, needs a DNA pol A/B/C gene on the DNA! (Transcription and translation) Not to mention all the other proteins required for transcription and translation.
Same is the case for RNA and RNA pol.
If the DNA/RNA formed first, how did it replicate without a protein?
If Protein formed first, then how did it came to existence without DNA/RNA?
Let's make a big assumption and say that nucleic acid formed for the first time and replicated without proteins. Is it possible for nucleic acids replicate without proteins? For example, a abiogenetically formed DNA sequence just randomly attracted its complementary strand and whatever could fit, fitted and somehow the phosphodiester bonds were sealed sans proteins. That sounds too implausible.
Would love if somebody provides sources with evidences of DNA/protein abiotically forming de novo sans enzymes, genes.

The straight forward answer is: we don't know. We don't have any direct evidence for what happened at that time nor any completely developed and coherent theories for how it worked.
The widely believed hypothesis is the "RNA World" hypothesis. RNA, unlike DNA, is capable of spontaneously folding to form catalytic molecules and thus avoids the needs for translation and transcription by proteins since it can bootstrap it's own synthesis. The idea is that, over time, the RNA developed the means to synthesize proteins and then started using DNA as a more stable storage molecule. The earlier RNA-based RNA polymerases were supplanted by higher fidelity protein polymerases over evolutionary time so we no longer see them in modern cells.

You can also add a note on the self replicating ribozymes


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Why do we find nature 'beautiful', from an evolutionary perspective?
Most people I know find nature beautiful and holidays generally involve a place that has 'natural beauty'.

I would say that beautiful is pretty subjective and has nothing to do with evolution. It is more something that humans find interesting, probably because of some romantic ideas.

there is an interesting TED talk about this, basically we don't find all nature beautiful, only certain aspects of nature have universal appeal, the ones that were advantagous for our ancestors like signs of water, food, and climbable trees. https://www.ted.com/talks/denis_dutton_a_darwinian_theory_of_beauty

We find valleys pretty. We find mountains pretty. We like sunshine and clouds.
I'd say all these have some advantages. Trees you can climb. In valleys you have protection. From mountains you have a good view across the landscape.
So yes it does make sense that we like nature. We like things that are good for us. Like fertile land and food.

Bright colors can attract a sexual partner as they are beautiful and are often a sign of good health. So, if you have bright and beautiful colors, you'll attract a partner to reproduce more easily than other and your genes will pass to the next generations. So, some animals are "beautiful" because of sexual selection.
For flowers, bright colors and perfume attract pollinators, so the brighter the better to reproduce.
Of course, as beauty is all relative, not all flowers or animals are "beautiful" according to humans' tastes. But they suit the environnement the organism lives in and whatever is needed to get to reproduce.
Sexual selection is not the answer to everything you find beautiful but it explains some.


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Which kit provides the highest yield and purity of extracted DNA from FFPE tissue samples?
I'm looking to extract DNA for sequencing from FFPE (Formalin fixed paraffin-embedded) tissue samples. I'd like to use a commercial kit that provides a high yield of good quality DNA.


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How to find name of the gene
Considering the kegg page, this page contains the description of the gene Edwardsiella tarda EIB202: ETAE_0074 . Now this gene has a name given in the page as : wabG.
Now considering another gene 1 and gene 2 , what is the name of these genes? How to I find the name of these gene and from which website?

The gene (gene-2) name is VC4260B_02250. Many microbial genes are named like that (like MTB with RVxxx). You can try downloading the genome annotation file for this species. It may have alternative names and ENSEMBL/Refseq ids.

then what is wabG

That is from a different species altogether.

i understand, but wont names be present?? like wabG??


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How to find the radius of gyration for a protein?
While going through the paper titled "GEOMETRIC ANALYSIS OF THE CONFORMATIONAL FEATURES OF PROTEIN STRUCTURES" by Manish Dutt, it talked about finding the radius of gyration of each protein structure. I am unable to understand how the radius of gyration has been obtained for the entire protein. I first find the root mean square distance between the centroid and the C alpha atom. Is the average of these distances the radius of gyration?

Pretty sure that there are library methods to calculate this - otherwise the formula for the radius of gyration of a set of points is on wikipedia? in any case, more of a bioinformatics question than a biology one...


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What would the presence of a hub metabolite in a metabolic pathway signify?
Say I have a metabolic pathway, consisting of multiple metabolites and reactions. On analyzing the pathway I find that among all the metabolite, one metabolite is the hub metabolite (hub metabolite is the metabolite such that maximum number of reactions involve that particular metabolite).
What is the significance of this metabolite or of this pathway?

It's hard to say without knowing what metabolite you're talking about -- all metabolites have different roles, and you won't learn much about it simply from network degrees. You have probably hit upon either a common cofactor like NAD or ATP, a small ion like H+, or a common group donor like glutamate.

@Roland isn't there any generalized perspective of it?

Not much, really ...  The "hub" metabolites of course give rise to many products, and they tend to be present in high concentrations (but not all are). But beyond that, you really need to look into the biochemistry. The examples I mentioned have completely different functions.

By your own definition you are talking about several pathways not just one. All you can say about the metabolite is that it's an important intermediate. What else would you imagine?

@David I am trying to figure out what else can be inferred from the hub metabolite... hence posted the question :)

Forgive me if I am wrong, but you sound like a computing science student who has been asked to perform some mathematical analysis on metabolism and is now wondering what the results mean and whether they are of any interest to biologists. I say this partly through experience and partly because I'd never heard the term 'metabolic hub', but on Googling find a paper from a computing science department using it. Note that paper refers to a metbolic network — as I said, several pathways.

@David you are absolutely correct. I am a computer science student. I have not been asked to do anything, but I am doing it on my own. And thanks a lot for the resource. Hope I will be able to get more insights regarding metabolic pathways :)

@Rishika — You were right to post, but try to make personal contact with biochemists. You need to find out whether there are real problems that your skills can solve. I know from experience that it can be difficult, and computing scientists have come up with things that are actually no use in the real world. In this case I would think you would just come up with things like ATP, NAD, glucose 6-phosphate, glutamate, the importance of which is already known. However if you can find a real problem, then your work can be worthwhile. Good luck.

@David would you mind if I could contact you somehow?

@Rishika — If you wish. You should be able to work out an email address from my profile.


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Why does a centrocyte have a cleaved nuclei?
Why does a centrocyte have a cleaved nuclei? Is there a biological reasoning behind this phenomenon or is it the nature of the centrocytes? Does the selected centrocytes proliferate too?


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Which gene regulatory network is the largest in human?
What is the maximum number of nodes involved in any gene regulatory network and which network is it, provided its from human?

Your questions come across rather strangely. You don't explain why you would want to know something like this. I gather from your bio that it is related to your PhD project, so I imagine you have a reason. However I would suggest you are more likely to get a response on SE Bioinformatics. There are more people there who know what a node is.

It is not quite my field and I don't know how to answer this question but it strikes me as it is likely that the definition about what type of interactions you would consider to deserve being represented by an edge between the two genes (genes are nodes in this network) would matter a lot.

@David i did not know there is SE Bioinformatics,... thanks!

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How do T cells deal with the obstructions in their path of migration?
When T cells move in the blood, are their any obstructions(other cells) while they migrate? If there are then how do the T cells overcome such obstructions in their path? Do they move past them or does their movement lead to displacement of the obstructions?

You might want to look this up https://en.wikipedia.org/wiki/Leukocyte_extravasation

@Polisetty thats a wonderful article you have shared. I did not know this had a term. Thanks a lot!


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Can two proteins activate/inhibit the same gene at the same time?
Suppose there are two proteins inhibiting a particular gene. Its not necessary that both will inhibit the gene at the same time instance right?
So if one protein has already inhibited that gene before the other protein, what is left for the other protein to inhibit this gene? It has already been inhibited right? What more does the other protein inhibit?

Probably the proteins are competing (like a % downregulation) to bind at the gene or they bind at different parts of the gene? it depends, do you refer to a specific example?

Inhibition does not necessarily need to be competitive, i.e. in the same place, i.e. the inhibitors work on different targets at the same time. Inhibition also need not be 'total', it can be partial. The inhibitors can be partial, additive or even synergistic (joint inhibition is greater than the sum inhibition of its parts). Single inhibitors can also sometimes inhibit multiple targets, so any 'extra leftover' inhibitors can work on other targets. Or work at different times in development; i.e. an inhibitor can have different targets in the embryo vs. the adult, or in tissue A vs. tissue B.

Can you give me a link to study more about inhibitors? These information that you gave me,  would these be available from any source?

This is general information available in any biochemistry or molecular biology textbook. I think you could start with Wikipedia, it has pages upon pages on molecular inhibition. A good starting point would be enzyme inhibition. Though many targets or processes can be inhibited - not only singular enzymes - such as the transcription of genes, or the progression of the cell into the next phase of its cell cycle, or the polarization of cells, and so on and so forth.

the inhibitors work on different targets at the same time.- does this mean multiple molecule of the inhibitor is in action at this time?

Are you referring to protein inhibition at transcription/ replication level or in general?     As you are mentioning the effect of protein on gene?

@Twinkle in general

Then its already explained in comment section. If you are particularly concerned at DNA level, then there are different proteins like transcription factors which bind to upstream elements located on DNA and regulate the DNA transcription.


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Identification: What animal is this?
Can anyone identify the species in those photos? Encountered in İzmir Turkey around 21:00 PM, scavenging human food refuse. The size is around that of an average adult stray dog.

Can't see in the pictures very well, but is there a reason you don't think it's an adult stray dog?

It's a canid, looks like a fox to me (the tail is quite long). I'm curious as to why it matters. Are foxes rare where you are?

As noted by others in the comments, this is most likely to be either a red fox (Vulpes vulpes) or a stray dog (Canis familiaris).
However, given that the photos, while poor in quality, show a distinct quite large fluffy tail, and what may well be dark ears (could also be shadows on the rear surface), I think this is a common red fox. Foxes are a very successful species that is common throughout the whole of Europe and northern Asia. They have adapted well to cities and are quite common in urban areas where they survive on rats, mice and other similar urban creatures as well as scavenging from rubbish/trash.
There are quite a few colour variations in fox fur, from a red through to white and tan. This looks like one of the lighter variants, possibly middle top or middle bottom in the image below:

 Image attribution: Darwin Museum, CC BY-SA 3.0 https://creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons


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How does the matter that makes up the fat of your fat cells ultimately leave your body--following weight loss?
I'd like to get some clarification on specifically how the matter from the fat reserves of the Adipocyte physically leaves the body.
In other words, if you were to somehow follow every atom in the fat reserves of the cells of a dieting person, then, via what hole would these atoms ultimately exit the body?
Is the answer to this question merely "exhaling through the mouth"? Or do they come out in feces too?
Note 1: This question is not to be confused with the question: "How does mass leave your body in general?" For there are several ways to accomplish this. (e.g. shedding skin cells, cutting off your arm, cutting your hair, sweating, dehydration, liposuction, bleeding, spitting, blowing your nose, etc...)
Note 2: Please see this other similar StackExchange post here:
https://physics.stackexchange.com/questions/2605/how-does-mass-leave-the-body-when-you-lose-weight

Yes, they are mostly exhaled. The carbon, hydrogen and oxygen that the fats are made of recombine to become $CO_2$ and $H_2 O$ and are exhaled.
It's the same overall chemical reaction as if the fats / carbohydrates were burnt, except it's by a different pathway, and the energy produced goes (mostly) towards driving other chemical reactions rather than becoming light and heat.

Hi thanks. Can you clarify the "mostly" part? Where else would they exit besides the mouth?

@tondog Some of the $H_2 O$ will come out in urine or sweat, for example.


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Why does open olive oil keep so long?
This is a question about the biology of microorganisms, not about food safety.
While most of our foods spoil quite quickly (it is recommended to throw food away after 2h in the danger zone), for some oils this is not the case: for example, opened olive oil may be kept for 18 or more months at room temperature.
This seems to indicate that while there are plenty of microorganisms around, pathogenic or otherwise, which readily feast on carbohydrates or proteins, there do not seem to be that many (or at least not in practically relevant amounts) that can metabolize our food oils, while our stomachs have no problem with that.
Why is this? Is it hard for microorganisms to break down the fatty acids (if so, for what reason), or do these oils usually have secondary constituents which are poisonous to microorganisms, but not to us?
Note that some bacteria can use fatty acids as energy source; that makes it even more interesting why it doesn't occur in our kitchens...

Oil Rancidification is a good read: https://en.wikipedia.org/wiki/Rancidification

There are plenty of foods that conserve long time after being open - sugar, flour, cereals, water, etc. This is to say that one needs to narrow the class of foods in question - which may already contain the answer.

That was a very interesting read, thanks @Science123, though it looks at it more from the point of view of the oils themselves (ie., also processes like autoxidation which do not involve microorganisms). Like the link I have in the question it also mentions E.Coli, and that there are natural anti-oxidants like Vitamin E... now the question remains - are these oils so chok full of anti-oxidants/microorganism killers that those have no chance; or are there little no no microorganisms that can survive on oils in the first place (and if so - why)...

True, @RogerVadim, but I fear if I open up the question for all kinds of stuff ("why do some kinds of foods not spoil") it may be a little too generic...

Bacteria and other Microorganisms are mostly water, and to replicate they will need more water. The water they need is not present in olive oil. Salts and other required elements are also not present in olive oil, at least not in sufficient quantities to  support proliferation of microorganisms.
Our stomachs indeed have no problem metabolizing oil, but if you had nothing else to eat or drink, you would die in short order.

Oh man, in hindsight the water aspect really seems quite trivial, and incidentally also answers why stuff doesn't grow on very dry stuff in general (pure sugar etc.). Thanks for opening my eyes!


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Number of chromatids Before S
Is it better to say 0 chromatids or 46 Chromatids in a human cell?
Because most of the webpages I have seen say 46 chromatids and some clarified that it is infact according to the definition 0 but 46 is more commonly used

Please add some citations to your sources.

Just as MattDmo said add some citation, the chromatids (you mean sister chromatids?) are synthesised IN the S phase so there are no chromatids before the S phase, I don't understand your confusion?


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Role of non-inflammation in H.Pylori positive people
Quoted from Saudi J Gastroenterol. 2009 Jul; 15(3): 201–207 publication :

Approximately 50% (over 3 billion) of the world populations are known
  to be infected with Helicobacter pylori, mainly in the developing
  countries. Among those, hundreds of millions of people develop peptic
  ulceration during their lifetime ....

I know that many people have H. pylori in their stomach, however, just a small percentage of them develop peptic ulceration. Does anyone know the role of this? Why don't more people develop any symptoms?

The answer is no, we don't know why some people are assymptomatic. Why? Because it's easier to prove causation than non-causation. But there is much more to H.pylori than ulcers. Chronic gastritis, lymphoma, gastric cancer, GERD, and other conditions (even bad breath) are associated with it. Given that H. pylori was only discovered 35 years ago (and taken seriously for far less than that), I'd say it's still early.

@anongoodnurse thank you for your reply. May be we should make a full genome sequencing of those H.Pylori on people with and without symptoms to see if there was a different type of H.Pylori that harmful and unharmful.

@anongoodnurse i known it's weird but I was healthy before - until I make an eradication H.P on my stomach, I started develop inflammation and GERD when the H.P become negative. I was though there must be a relevant between the eradication of H.P and my symptoms. I'm trying to find an evidence that some type of H.P may protect the lining of duodenum and stomach  from acid and bile. As it can produces urease to neutralize gastric acid and other mechanism to resist bile.

No, to my knowledge, H. pylori is not protective at all. BUT  our knowledge of all its effects is in its infancy. The present stance is if it's detected, it's treated (100% of the time), even though risks of treatment exist, and even if the patient is assymptomatic. I have some doubts about this approach, but as my mother died of gastric cancer and was discovered to have had H. pylori, I should be more open to this. I don't know. If I have time later today, I'll scrape up an answer.


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How our body produce different T-cells?
I've heard in many documents said that :

There are 25 million to a billion different T-cells in your body. Each
  cell has a unique T-cell receptor that can fit with only one kind of
  antigen - quoted from askabiologist.

But I haven't found the mechanism of this. How our body produce too many different T-cells? Does our genome need to have 25 million to billion genes to encode for 25 million to billion unique receptor for those T-cells? Does each T-cell have a different gene region on their genome or they have a different turned-on/turned-off genes ?

You want to look for receptor re-arrangement and editing.

https://en.m.wikipedia.org/wiki/V(D)J_recombination


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Can CRISPR-cas9 be used to insert a large gene?
I would like to insert a 1500 bp or longer gene to the broken site in E.coli (or may be bacillus subtilis which support NHEJ) after cut with Crispr-Cas9. Is this possible for both NHEJ or HDR?

CRIPSR-Cas9 can be used in eukaryotes to insert much larger fragments (using two different sgRNAs and HDR), so in in principle this should be possible - I'm not sure if it will work in bacteria though.

@Nicolai thank you very much, can only one sgRNA work?


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Can a protein go outside of nucleus after go inside with nuclear localization signal (NLS)
To make a protein (for example Cas9, GFP...) able to enter the nucleus, we need to add a NLS tag for it. So will it able to go outside the nucleus after get inside ?

It seems that I need to add a NES (nuclear export signal) if I would like to make it able to export the nucleus : https://en.wikipedia.org/wiki/Nuclear_export_signal  .


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Glass petri dish to replace plastic petri dish?
I never use a glass petri dish before, but I just wonder if I can use it to replace for plastic petri dish because it can reusable. The only thing I worry is , in a Fridge's user manual, it said that do not put glass container into the freezer (usually -20 oC) because it can be damaged/break and even explode. So do a glass petri dish have any special design to prevent this damage?

Glass labware is usually made of borosilicate glass which is resistant to temperature changes, so putting a glass petri dish in a -20°C freezer should not be problematic, at least with respect to glass cracking because of temperature changes. I think the warning on your freezer is probably meant to warn against closed glass containers filled with liquid; as water freezes it expands and may mechanically break the glass, but for a petri dish is should not be an issue.
I would be more cautious about heat shocks with a -80°C freezer, though; in my experience at that temperature there is still a risk if the glass is not of good quality.
On a side note, depending on what you use the petri dish for, the surface chemistry  may be different from the polystyrene of plastic petri dishes, and if you are growing cells directly in contact with the surface, switching to glass may change their behavior.

Thank you very much. I'm not sure if it was borosilicate or not. Just found it on an online store and they don't provide much info. Let me try it myself.


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Pathophysiology of babinski sign in spinal cord injury?
How can we differentiate between upper motor and lower motor neuron lesions on the basis of babinski's sign ?

Could you add some more background to the question? I.e., what is babinski's sign?

shouldnt people (to whom the question is intended to be answered by) know it ?

The SE network, including Bio, is not just for your answer only, it is built for the community at large. Supplying background information aids that purpose.

Short answer : If the Babinski sign is positive in adults, it indicates an upper motor neuron lesion.
Long answer :
The plantar reflex is an interesting reflex since it has two physiological responses. One in kids 1-2 years of age and another in the rest. It is one of the primitive reflexes that are present in infants but are cortically inhibited later in life.
The primitive response to the plantar reflex is extension of the hallux and fanning out of the toes. Once the kid is around 1-2 yrs of age, the corticospinal tracts are fully myelinated and this primitive reflex is inhibited leading to the flexion of the hallux.
Extension of the hallux is regarded as a positive Babinski sign while flexion is sometimes called negative babinski.
So in an adult, due to cortical inhibition of the primitive reflex, the plantar reflex should yield flexion of the hallux. But if it pathologically shows a babinski positive, it indicates the absence of cortical inhibition - an upper motor neuron lesion. This might be a serious neurological issue and you'd want to do a CT brain, CSF study or an MRI spine to localise the lesion.
On the other hand a negative babinski in kids who should be showing the primitive reflex, may be showing signs of spasticity. This should direct us towards progressive neurological disorders like cerebral palsy.


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Two sets of chromosome and the sequencing output
Humans have two sets of chromosomes that are not connected in each cell. Am I correct?
I assume while sequencing DNA both of these sets have to be sequenced and the output have to be provided in some order - i.e., paternal set followed by maternal or vice versa, though it may not be possible to know which is paternal and which is maternal.
(I know there are different types of sequencing techniques and output may differ depending on the technique. Here I am speaking of the general case). I tried clarify this question myself. But may be this is such a basic thing that no one seems to touch upon this aspect.

Note for observers: previous question as referred to.

For many biological research questions it is not important to know, if the sequence comes from the paternal or maternal chromosome. - However - as you pointed out - there are different approaches of obtaining the sequences. Some of them would allow to distinguish different chromosomes (see https://en.wikipedia.org/wiki/Contig  ).   In practice: if you would like to know if a variant of a gene comes from the father or mother it is easier / cheaper to sequence them (or do some other faster/ cheaper test on them).

If an answer given to a question is unclear, you can do two things: Either write a comment or adapt your question. Showing the kind of attitude you do "I don't understand the current answer and don't care to do so" is actually insulting towards the people which invest time to write an answer. Actually not the best idea.

I believe the question boils down to simply: How are heterozygous results reported from the sequence alignment process?

This is very similar to your previous questions, but apparently you are not understanding the explanations we are giving, so I'll try again, by giving a (hopefully not-too-technical) explanation of how next-generation genomic sequencing works. To avoid confusion, we'll assume we're working with human samples.
First, many individual cells are collected (the number depends on the application, it can range from 1 cell to millions or more), and their DNA is collected. This process destroys the cells, and all of the copies of all of the chromosomes are mixed together. As mentioned in your other question, there is no possible way to determine which chromosomal sequence is maternal, and which is paternal. Scientists typically don't even think about this.
Next, the collected DNA sample is purified and broken down into small pieces, then ligated to certain adapters to label them for the sequencing reaction. The sample is then amplified in a standard PCR to create starting material that is many times more plentiful than before. This is the DNA library.
Finally, the sample is ready for sequencing. What exactly happens next depends on which sequencer you're using - Illumina, Ion Torrent, 454, or SOLiD are the most frequently-used instrument brands. Within each brand, Illumina for example, there are multiple different kinds of sequencing.
However, we'll just gloss over all that and get right to the output - the instrument produces a file consisting of "reads" from the reaction. These reads are DNA sequences consisting of As, Ts, Gs, and Cs - the "letters" (also known as "bases") of DNA. The lengths of the reads vary by technology and instrument, generally in the range of 100 to 700 bases. One machine, though - the PacBio RS II, can produce high-quality reads up to 14,000 bases, although to my knowledge it is not in widespread use.
Here is where the computers come in. The individual reads overlap each other to varying degrees, depending on the quality of information you're seeking and whether or not you're looking for rare events, such as a small population of mutated cells taken from a heterogeneous tumor. For our purposes, we'll say our sequencing run resulted in a 25-fold overlap, meaning each base in the original DNA sequence of the sample donor was sequenced an average of 25 different times. The computers can then "align" the sequences, either just among themselves, without a template, or, more commonly, to a pre-existing sequence template, such as a reference genome. Eventually, the computer will spit out two sequences - the forward and the reverse strand (although typically you'd just pick one strand, and use the reverse strand for error-checking). This sequence is the average sequence of the chromosome, or other region of DNA being targeted.

From Wikimedia Commons: Mapping Reads.png
However, one can pretty easily detect mutations, such as single nucleotide polymorphisms (SNPs), deletions, insertions, etc. In the case of a SNP (pronounced "snip"), one allele of a gene has one sequence on one chromosome (lets say ATTCGTAAC) while another allele of a gene on the other chromosome has a single-base change (ATTCTTAAC, for example, where the G was changed to a T).
The point, directly relating to your question, is this: The final sequence that eventually comes out after all the computer wrangling is a single sequence with certain areas that may differ from chromosome to chromosome, or cell to cell in the original sample. There is no way to determine if the G in our example above was on the maternal or paternal chromosome. There is also no way to tell if, 20,000 bases down the line, another mutation is on the same chromosome as the G, because no single read can (currently) span that entire length. You might have a pretty good chance of determining that if the other mutation is, for example, 300 bases away, because many technologies can perform high-quality reads longer than that, so you'd just have to find the individual ones that contain both positions.
I know this was a little long-winded, but hopefully I was able to answer your question.

Matt, if the guy didn't understand first time, why did you give such a long and technical answer second time? It would be enough to say what's in your final paragraph that he'll probably never get to. i.e. The result is a mixture of both chromosomes, so we only know if the sequence at any point is the same for both or different. (And because of crossing over there's no such thing as a maternal or paternal.)

@David I had to try - the answers to the previous question weren't that great, and while the OP said s/he didn't care about the details of sequencing, I figured that actually explaining how sequencing works in general terms would help them understand why there is no "order" of which chromosome comes first. And, I had some free time, so it wasn't that big of a deal.

@David regarding crossing over: that happens during meiosis in the parent, when germ cells are being formed. The egg is haploid, as is the sperm, but after they join the chromosomes do not cross over again.

Whoops. Shows how little I know about classical biology.

@MattDMo Could you please explain the last paragraph of your answer? You said (in your example) that we can't determine the G in our sequence was on the maternal or paternal chromosome. Won't both the alleles on the homologous chromosomes be sequenced? If yes, do we have sequences of both the chromosome (be it or be it not distinguished) in the final sequence? I don't know the intricate details on this subject, but it occurred to me whether or not we have a single allele of a gene in the final sequence or both the alleles (in case of diploid) and how does this happen for both the cases?

@Ramil All DNA fragments in the sample are (theoretically) sequenced, so both alleles of a particular gene will be sequenced, but unless we already have the paternal and maternal sequences as a reference, there is no way to know if the G came from the mother or father. The whole point of my answer (and the last full paragraph) is that the final product is a single sequence, with electronic "pointers" indicating areas of heterozygosity, such as the G→T difference. However, we can't tell which original chromosome the G was on vs. the T.

@MattDMo If both the alleles of the genes are sequenced, how do we get a single sequence for each gene? And the heterozygosity you mentioned, is it with respect to the reference genome?

@Ramil Differences between alleles are generally very slight when it comes to the DNA sequence - perhaps a few or only a single base difference. I already explained how these differences are detected and reported in the final sequence. Depending on the read length of the instrument, you may not be able to show that multiple differences are in the same allele - you'd need a different technology such as RNA-Seq for that. I used the term heterozygosity to refer to the difference between the two alleles possibly present in the sample.

@MattDMo You mean the forward and the reverse strand that you mentioned gives the difference and the final sequence is the average?

@Ramil No, the forward and reverse strand have nothing to do with determining variations between alleles, they are only used to add more confidence to reads, as they are perfect complements of each other. The final sequence uses this code, so in our example instance the base would be reported as a K (either G or T). With a high enough confidence in this call, one can assume that both G and T are present at that locus, meaning two alleles. You can also go back to the original reads and see that ~50% are G and 50% T.

@MattDMo Ohh! Thanks a lot. Makes sense to me now.


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What concentration of sugar is optimal for baker's yeast fermentation?
I'd like to do an experiment on what concentration of sugar would be best for fastest yeast fermentation. I'm thinking to put some active dry yeast into different concentrations of sugar water and measure the fermentation activity after a certain amount of time (like 15 minutes or so). I know at a certain concentration the yeast will effectively die as the sugar solution becomes hypertonic, but I don't really know what range would be most effective right now. Any papers I've found are on yeast for alcohol.

When glucose and fructose are fermented separately, the uptake profiles indicate that both sugars are utilized at similar rates. However, when fermentations are conducted in media containing an equal concentration of glucose and fructose, glucose is utilized at approximately twice the rate of fructose. The preferential uptake of glucose also occurred when sucrose, which was first rapidly hydrolyzed into glucose and fructose by the action of the enzyme invertase, was employed as a substrate. Similar results were observed in the fermentation of brewer's wort and wort containing 30% sucrose and 30% glucose as adjuncts. In addition, the high levels of glucose in the wort exerted severe catabolite repression on maltose utilization in the Saccharo~ myces uvarum (carlsbergensis) brewing strain. Kinetic analysis of glucose and fructose uptake in Saccharomyces cerevisiae revealed a Km of 1.6 mM for glucose and 20 mM for fructose. Thus, the yeast strain has a higher affinity for glucose than fructose. Growth on glucose or fructose had no repressible effect on the uptake of either sugar. In addition, glucose inhibited fructose uptake by 60% and likewise fructose inhibited glucose uptake by 40%. These results indicate that glucose and fructose share the same membrane transport components

References
D'Amore, Tony, Inge Russell, and Graham G. Stewart. "Sugar utilization by yeast during fermentation." Journal of industrial microbiology 4.4 (1989): 315-323.
Thirwell, A.J. and R.L. Busby. 1982. Liquid sugar as a brewing adjunct. Inst. Brew. Proc. Conv. (Aust. and N.Z. Sect.) 17:77 84.
, http://www.123HelpMe.com/view.asp?id=121963

you can also add this citation because the other two cannot be found (but they seem valid because they are cited)


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0.1 M sodium citrate in 10% ethanol and DNA solubility
I understand how DNA precipitation works in the presence of salt (such as 0.3 M sodium acetate or 0.2 M sodium chloride) and alcohol (30 ~ 50 % isopropanol or 60 ~ 75% ethanol)
However, in the Trizol kit manual, DNA could be washed and precipitated in 0.1 M sodium citrate in 10% ethanol
At only 10% ethanol and 0.1 M sodium ion, how can DNA be in a "compact/insoluble" form so it can be precipitated by a low speed centrifugation (2000 x g for 5 mins)?

The sodium ions will bind to and neutralize the (-) charge on the phospho backbone of DNA. This reduces hydrogen bonding sites for water, which then results in less solubility.
Edited for clarity and because I didn't answer the question the first time. Sorry about that.
The extraction of DNA is from the interphase layer, which is a very small fraction of the original sample. The extraction of the interphase layer is then mixed with 100% EtOH (300 ul per 1.0 Trizol used in that sample). This should actually be 60% or more EtOH based on my experience using this method.
That is the precipitation step.
The fact that the wash has only 10% EtOH and 0.1M sodium citrate and that is still sufficient to keep DNA precipitated revolves around 0.1M sodium citrate is usually 0.3M sodium ions (sodium citrate can be mono-, di- or tri-sodium, but unless specified..sodium citrate implies tri-). Remember for the wash, you don't need to do a quick precipitation, you just need to prevent it from solubilizing again.
I am removing my comments that contained the same information.

This doesn't address why only 0.1 M sodium citrate and 10% EtOH is used while most precipitation protocols require 0.3 M sodium acetate in 70% EtOH


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Genomic DNA extraction protocol by salting out with NaCl, how to improve yield
In these papers

A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies
A simple salting out procedure for extracting DNA from human nucleated cells
Modified salting-out method: high-yield, high-quality genomic DNA extraction from whole blood using laundry detergent.

In brief, red blood cells are first reduced/removed. Nucleated cells are lysed in the presence of SDS and genomic DNA are released. The resultant lysate are gooey. Addition of NaCl results in protein precipitation which is then removed by centrifugation. The genomic DNA is believed to not be precipitated by salt and thus remain in the supernatant which is recovered by ethanol/propanol precipitation.
Typically, ~30 µg of DNA is obtained per mL of blood.
I tried the salting out method recently and the yield is quite low (~ 10 µg per mL of blood), so no where near the published figure. In comparison, I obtained ~ 30 µg using phenol/chloroform from the same blood sample. I have tried using NH4Cl and still get a low DNA yield. I believe one of the reasons is that a lot of genomic DNA get trapped in the protein precipitates after addition of salt.
What can be done to prevent or minimise genomic DNA being trapped with the protein precipitate?


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Is Infra Red light safe to use on your scalp?
I own an Anodyne Infrared therapy device which I use to treat ligament/tendon/muscular pains and it works nicely.

I see other infrared products used to combat hair loss (e.g. https://www.amazon.com/dp/B01B29PCUU), but I don't know the nuances of different infrared devices. Is it safe to use the device intended for the above uses on my scalp? I'd rather not purchase a separate infrared device for my scalp if I own the necessary technology already.

These are entirely different devices. First off, the Anodyne product is truly far-infrared, emitting at 890 nm (infrared is above ~650-700 nm). However, the hair loss product you linked is far-red/near-infrared, with laser diodes emitting at 650 nm (which is why it glows red). If you put the Anodyne product on your skull, you'd just heat up your brain, possibly burning any hair you have left. (Well, maybe not, but it sounds kind of funny.)
I would strongly suggest you don't try regrowing your hair using an instrument designed to relax your muscles. I will give you a recommendation - read the small print very carefully. The hair product is only recommended for a certain type of hair loss called Androgenetic Alopecia. Please consult with your doctor to determine if you actually have this condition, otherwise your investment of US$600-700 will be completely wasted.

Good to know. Thank you for the insight. Looking at this pic, I probably do have Androgenetic Alpoecia but like you say it's worth checking if this is true before I get my hopes up and spend effort (more burdensome than the money!).


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Can the NADPH/NADP+ ratio affect the FMN to FMNH2 ratio in the complex I of the mitochondria?
This is the reaction:
FMNH2 + NAD(P)+ <-> FMN + NAD(P)H + H+
The reaction works either with NADH/NAD+ or NADPH/NADP+
I know that the NADH/NAD+ ratio affects the FMN to FMNH2 ratio
But does the NADPH/NADP+ ratio affect the FMN to FMNH2 ratio in the complex I of the mitochondria?

No, because FMN is bound to the complex covalently.

@SciEnt — if you are going to answer questions please do so as an answer not as a comment. When you click on the comment link this is made quite explicit. Ignoring this injunction undermines the way Stack Exchange operates.


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Is there difference in stomatal density in young and mature leaf?
If stomatal density varies in young and mature leaves then what may be the reason for this.which surface of the leaf has more stomata?how to distinguish abaxial and adaxial surface in monocot.


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Biological & Evolutionary Reasons for Palm (Bi)Symmetry

The fingers of the human palm exhibit a (bi)symmetrical pattern with regards to their size, in the sense that the thumb and the pinky are almost the same size, and the same holds for the index and ring finger. I was wondering what the biological imperatives and/or evolutionary advantages behind this physical characteristic are.

The only rationale I personally am able to come up with is that this particular arrangement might be optimal or ideal for grasping, handling, and manipulating objects, but am unsure of its truthfulness, and, even if correct, I would still be interested in exploring other possible avenues.

Possible duplicate of What is the evolutionary cause for various finger lengths?

The thumb is NOT the same size as the pinky.  You are perhaps looking only at the first two bones of the thumb.  Look at all three bones, and you will find that it is longer: probably longer than any of the other digits.  (At least it is on my hands.)

@jamesqf: All fingers, not just the thumb, extend into the palm of the hand.


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Has anyone tried using luminescent conjugated oligothiophenes to detect cellulose in a microbial biomass? If so is it accurate?
I recently found this paper http://www.nature.com/articles/srep35578 which describes a "new" method for detecting cellulose. As I'm not an expert in the field I was wondering if other people have used this to detect cellulose in microbial biomass (specifically E. coli biofilm) and not just plants. It seems like it should work but maybe I'm missing something.


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Rate-determining steps in enzyme catalysed reactions
According to my chemistry book, there are 3 simplified steps within an enzyme catalysed reaction:

S + E → ES
ES → EP
EP → E + P

Where S is substrate, E is enzyme, ES is enzyme substrate complex, EP is enzyme product complex and P is product.
It is my understanding that at first, when substrate concentration is low the rate determining step is step 1, as this is the slowest step in the mechanism.
When you increase substrate concentration to a certain level, where there are no free enzymes remaining to bond with them, adding more substrate will not make the reaction faster, so the order has become 0 with respect to substrate conc.
Is the rate determining step now 2 or 3? I thought it would be 3 as that is the step that frees up more enzymes which could go on to catalyse more reactions. My book says that it is step 2, as "it depends on how fast the ES can convert into EP". But surely this step won't free up more enzymes to catalyse reaction further?
Is the book correct? Can anyone help me understand this?

This is enzyme and substrate concentration specific, since the reaction rate depends on the reaction rate constant k that depends on the enzyme. However if there is a large amount of P present in the solution the EP -> E + P reaction slows down so this can be the rate determining step. On the other hand if you dynamically remove the P molecules from the system the ES->EP can be the rate determining step.

Is it enzyme specific, or is it related to the amount of P in solution? Your first sentence and the second two seem to be be giving two separate answers. -- FWIW, I agree with the answer of "enzyme specific". Even in the absence of appreciable amounts of product there are enzymes which have a slow off rate of product release, and it's this product release which is the rate limiting step.

@R.M. You are right, my explanation was poorly constructed. I wanted to say that it is both enzyme specific and depends on the concentration since the reaction speed depends on a k constant and on the concentrations of the reactants. This constant depends on the enzyme.

You can (and should) edit your answers to add additional information and to clarify things that might be confusing. (Edits are not just for typo correction.) Just click the "edit" link in the bottom left of your answer.


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Why do cell membranes let small non-polar molecules through but won't let small polar molecules through?
If the hydrophobic hydrocarbon chain of the phospholipid prevents the movement of polar molecules through the membrane. Why does the hydrophilic phosphate head of the phospholipid not prevent the movement of non-polar molecules?

You might be interested in this.

See if this helps: http://biology.stackexchange.com/questions/52371/why-lipophilic-molecules-can-pass-phospholipid-bilayer-in-spite-of-2-hydrophili/52384#52384

Polar molecules needs electrochemical gradient and protein carrier. ...whereas non polar molecules needs kinetic energy and these molecule continuously bouncing to come out from the cell membrane through the channel provide by lipoprotein structure of cell membrane and concentration gradient also effective for movement of molecules all types of molecules.

The plasma membrane consists of hydrophobic and hydrophillic characteristics. Towards the outsides, they are hydrophillic, so they can create bonds with water. The insides are hydrophobic, allowing no water inside and keeping them tight together due to the polar forces.
An non-polar particle (if small), can pass through this because it does not interfere with the hydrophobic/hydrophillic (polar) nature of the plasma membrane. However, polar particles would not have the opportunity to move in, because the insides (hydrophobic) are literally afraid of water, or charges, don't allow polar substances to pass through.
So only hydrophobic (nonpolar), gases, and small particles (nonpolar) can pass through. There are exceptions of $H_2O$ passing through the membrane in small amounts because their electric charge is very minor.

First, we should understand what causes molecules to be hydrophilic or hydrophobic.
A molecule is hydrophilic if it contains atoms with different electronegativities, that is atoms that pull electrons with different strengths. The factors determining the strength of the pull are the size of the atom (including the pre-existing electron shells) and the number of protons. Make the atom too big and electrons are too far from the nucleus, make it too small and there is not enough protons to pull the electrons. An atom that has a balance between these two factors is oxygen which has the second highest electronegativity in the periodic table. Oxygen was thought to be the maker of acids, which is literally in the name. Now we know this is not the case because all you need is to be sufficiently more electronegative than hydrogen so that it becomes essentially a proton that bonds ionically with you and is released into the solution, becomes looser. Anyway, the electronegative atoms in a polar molecule form hydrogen bonds with oxygen and hydrogen in water molecules because they have opposite partial charges, partial because the bond is not ionic. This includes water forming hydrogen bonds with other water molecules that gives rise to cohesion, surface tension as well as hydrophobic interactions which we shall explain in the next paragraph.
What happens with hydrophobic interactions (not bonds) is that water molecules want to pair with each other so they push the so-called hydrophobic molecules out of the way and clump them together. They are not hydrophobic in the literal sense, they essentially don't pair with water because they are not polar enough. Examples are hydrocarbons, where hydrogen and carbon have very close electronegativities.

The cell membrane is formed of phospholipids, these are molecules with polar hydrophilic phosphate heads and non-polar hydrophobic fatty acid tails. They align so that the phosphate heads face water and the fatty acid tails hide inside the membrane.
Polar molecules can't pass the membrane because they are being pulled by water outside and not being pulled by the membrane which has the hydrophobic fatty acids inside. Channels essentially form hydrophilic passages for these polar molecules so they can pass according to their concentration gradients.
Non-polar molecules are essentially hated by both bodies of water, extracellular and intacellular fluids. The question then becomes: why don't they stay inside the membrane with the hydrophobic fatty acids? Well, we need to think about this in terms of forces. You essentially have two forces:

Surface tension of the water that lines both sides of the membrane and keeps the hydrophobic molecules inside.
Pressure force (or normal force) that arises as the hydrophobic molecules accumulate and push on the surfaces of the membrane.

It has to happen that eventually the hydrophobic pressure overcomes the surface tension unless you put infinite amounts of salt in the water (increases the number of bonds) or you freeze the water which increases the surface tension. It then becomes clear that the molecules are more likely to have a net movement towards the body of water that initially had less of them. This is known as simple diffusion. It's also good to know that membrane fluidity which is the continuous lateral movement of the phospholipids parallel to the membrane constantly breaks other bonds between the hydrophobic molecules and the fatty acid tails like Van der Waal forces.

Outside membrane there in water and inside membrane there is lipid.
Hydrophilic molecules are more stable in water as compared to lipid so they prefer to stay in water and not go inside lipid.
Hydrophobic molecules are more stable in lipid as compared to water so they prefer to leave water and move freely into lipid.
You are saying that hydrophilic part of membrane will obstruct the movement of hydrophobic molecules but do not forget that they are already in water, which is polar, so it doesn't matter to them.
Analogy :- 'If you are on roof of your house you can very easily jump to roof of adjacent house' similarly hydrophobic molecules which are already unstable in water can move towards hydrophilic part of membrane because they are equally unstable there.


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Why do organisms not just have more genes to account for the possible gene products generated from alternative splicing?
Alternative splicing can generate many gene products from single genes, by combinatorial inclusion / exclusion of introns / gene segments. What is the evolutionary advantage of having a complex processing system that allows for alternative splicing, rather than just having more genes in the genome that directly encode the numerous protein products that an alternatively spliced gene could provide?

Your thinking about evolution is basically flawed. You can ask why a particular development might be advantageous to an organism in particular circumstances, but evolution isn't directed, so asking why some other mechanism didn't evolve to achieve the same thing is invalid. Nature has more than one way of killing cats, and eukaryotes make use of duplicated genes. It might help you to think about how alternative splicing is used in a eukaryotic context.

Does this answer your question? Why do some bad traits evolve, and good ones don't?

@mgkrebbs — The question is poor, but it is not a duplicate of the one you cite. It has nothing to do with good or bad traits as far as I am concerned, so I cannot vote to close it on that account. If I have time next week I will suggest ways of thinking about the questions it actually provokes.

A few factors to consider will be as follows:

This paper shows that compared to prokaryotes, eukaryotic genomes are resilient to the increase in genomic material. They show that the energetic cost of genome maintenance is under less selection pressure in eukartoyes compared to prokaryotes. Thus, multiple genes coding for multiple splice variants may be possible in certain cases.
Gene expression is a tightly regulated process and requires production of multiple repressors, activators etc. Having multiple genes for each splice variant will require transcriptional silencing of all but one / few variants (many tissue types express a specific splice variant). You can imagine that for a large number of genes for their splice variants, regulation is going to be difficult.
Introns have also been hypothesized to confer a degree of resistance to deleterious mutations as there may be no change in the protein ever if the intronic regions get mutated.
Research also indicates that introns are responsible for inhibiting formation of RNA - DNA hybrids during transcription.

In summary, although having multiple genes coding for multiple splice variants is possible at the genomic level, their regulation will be difficult. Moreover, introns have been proven to be beneficial for genome integrity.

Energy cost arguments are really unconvincing. Think about polyploidy. I think (and have written several times) that you really have to guard against self-fulfilllment arguments on molecular evolution questions. It is like this so it must be better than (what) so any argument I can think of justifies it.

@David I have changed my first point and included a reference for the same.

The question asks about evolution, and makes a basic mistake of thinking that there is a goal that the organism is trying to evolve to, and that it has some sort of choice as to how to get there. All one can actually say in cases like this is what the particular advantages are for an organism that "chances" on this new possibility, and whether there are any mechanistic reasons why it might evolve rapidly — perhaps more rapidly than other mechanisms. Don't fall into traps set by poorly thought out questions.


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Why are stem cell therapies more preferred (theoretically) over current measures?
i understand that when stem cells are used to treat injuries using induced pluripotent stem cells (IPS), they can prevent the risk of having any tissue rejection and thus, there isn't a need for use of immunosuppressant drugs.
However, based on the researches using animal models thus far, I note that surgeries are still the main mode of delivery of such stem cell-regenerated organs/organoids. Meaning, to transplant a part of a organ or a tissue into the animal model, a surgery still needs to be done - how is this different from current measures?
Specifically, how are stem cells going to aid or further research into areas such as curing heart or lung diseases and I wonder how are these methods going to be better than current ones.

Stem cell therapy was never going to replace surgery, and it isn't supposed to. We just don't have the tools to move stuff around inside the patient without breaking the skin.
Stem cells therapies offer replacement parts for organs that can't regenerate themselves. For example, after a heart attack the heart often forms a scar where heart tissue has been injured or died. The scar often doesn't conduct electrical signals properly or doesn't beat at all, both of which are a problem for a heart. The scar can't be surgically removed, because there's nothing to replace it with. Stem cell therapy would provide new heart muscle to replace the damaged tissue.
There are of course exceptions, some stem cell therapies are injected and left to 'settle' in the right tissues. That kind of therapy generally doesn't replace a surgery either, because that kind of problem can't be fixed with surgery at all.


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Genomic DNA resuspension after ethanol precipitation
I am having trouble resuspending purified human genomic DNA.
The genomic DNA is purified using phenol:chlorofom from ~ 1 mL of blood. After ethanol precipitation, I normally see a large pellet which is then resuspended in 150 uL of TE (10 mM Tris pH 8.0, 1 mM EDTA).
But the resulting DNA solution is extremely sticky.
There are the options I have tried:
1) Incubation at 37C for 1 hr to overnight
2) Incubation at 50C for 1 hr to overnight
3) Incubation at 65C for 1 hr to overnight
The 65C incubations for up to 3 hours do make the DNA solution less sticky, but in the mean times, cause increasing DNA smearing when running on agarose gel. After overnight incubation at 65C, the DNA solution is no longer sticky but shows extensive smearing on gel, indicating DNA degredation/fragmentation at high temperature.
I have also tried resuspending the DNA in 8 mM NaOH, then neutralise it with Hepes, but this doesn't help either.
I am thinking to try silica/glassmilk beads based methodology. Will genomic DNA captured in silica beads be easier to elute and resuspended without the "sticky" issue.

Sounds like an impurity in your prep as opposed to they way you're resuspending. If silica worked it wouldn't be because solubilization of the DNA was easier, but rather because impurities were more efficiently removed. It's not like if you have completely pure DNA on a column vs. in a pellet the pellet could be more sticky upon solubilization; the end product of dissolved DNA would be identical. Have you checked the OD260/280 of the sticky stuff? Or, maybe the DNA is just too concentrated; maybe try more solvent? Some people on the internet are saying they have this problem from over drying.

Purified DNA have a good 260/280 (~1.85) and a nice graph (nanodrop). I don't think the DNA is over dried, as soon as it's washed in the 70% ethanol, I aspirate all the alcohol and put TE into the bottom of a tube immediately.

When you say 'sticky' do you mean viscous, a solution with high viscosity? That is precisely what you would expect, or predict, for purification of intact, high molecular weight, genomic DNA.  Your own data reveals this to be the case, as assayed by agarose gel electrophoresis, when the viscosity of the solution decreases the DNA fragments in the tube get shorter. It follows that longer fragments of DNA are likely causing the increase in viscosity. The question is, what do you need to do with the DNA?

What about proteinase K? You mentioned the phenol/CHCl3 extraction, but that is typically preceded by a digestion with proteinase K at 65 C in the presence of SDS and EDTA.

'Viscous' in the word. I tried with and without proteinase K and noticed that proteinase K can be omitted without affecting the quantity nor quality (absorption spectrum). The DNA is for next gen sequencing. It's true that DNA will be fragmented in most sequencing platforms. But we want to keep the DNA as long as possible for something like pacbio which requires long intact DNA

What kind of concentrations are you getting in your DNA resuspensions? If you are getting DNA concentration higher than 1µg/µl, you should consider diluting the DNA. Otherwise, the viscosity is unlikely to be related to the concentration.

Just a thought, have you tried eluting the DNA in Molecular Grade Water instead of TE?

For DNA which are supposed to be used in downstream applications like sequencing or transformation, elution with Water instead of TE buffer is frequently done.
I agree longer genomic DNA can be sticky upon elution, but if by chance the DNA is not entirely dissolved when you add the eluant (you see some very small clumps of flakes instead of a homogeneous clear solution) , that may be because of the presence of low amounts of alcohol (organic solvent). That's why it is recommended that after aspirating the alcohol, you should leave the tube opened for ~10 minutes for the trace amounts of alcohol to dry out before you add the eluant.

Sorry if you have done these things already, just wanted to be sure.
Hope this helps!

It's true that water is sometimes recommended for elution. But in general TE is better for (1) resuspension as the alkaline pH is better at "solubilising" DNA and that the pH of water can be fluctuating between 5 ~ 7; (2) stability as the EDTA prevent extraneous nuclease, Qiagen has a related note


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DNA Topology. Question on twists and writhes
Hi guys there is a question which has been driving me crazy ever since I saw this video(https://youtu.be/az2c6UbEdug). At 4:50 the guy says that when a right-handed circular DNA starts forming a right handed interwounding writhe the DNA must adjust by twisting more(You can see the number goes up to 8 from 5 in the equation) and that when an interwounding writhe is done in the opposite direction it must twist less. To me this doesn't make sense at all. I thought that as you interwound to the right the twisting should lessen and when you interwound to the left the twisting should increase. Can someone explain(or show a very clear diagram/illustration which explains this) please??

It is all explained here in Wikipedia. If you want to make a 3D model of your own, you can use two pieces of tygon tubing (like the rubber hose for a Bunsen burner), that are both circularized and attached with connectors that can be opened and closed--that lets you simulate nicking and re-sealing the strands.


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Why are eye defects so common?
The title says it all, what makes eye defects so common in the world? Whereas defects of any other body part is quite uncommon, I searched online and one of the articles said that 6 out of 10 people wear glasses, I think that is a big percentage of people with eye defects, BTW I'm myopic and I wear glasses too. Are all body parts defective to a certain degree, but It seems more pronounced in the case of eyes?
P.S
I know nothing about biology, I appreciate if someone could explain it with preferably less technical terms, this is my first question on BSE, let me know how I can make the post better.

@Roland I think that answers my question, you can mark this as a duplicate


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How is "fine mapping of pelvic regulatory region" done in the stickleback PitX1 paper?
I'm working through this paper for a class. I'm a bit confused by the methods they used in one experiment.
So the researchers are studying spine development in stickleback fish. They noticed some fish have spines and some do not. They have a good hunch that spine development is under control of PitX1. They work out through cross breeding spined/non-spined fish that spine development is regulated in cis.
They then attempt to find what piece of intergenic DNA regulates PitX1 expression. And this is their explanation of how it was done:
"To further localize the position of the cis-acting changes, we looked for the smallest chromosome region co-segregating with bilateral absence of pelvic structures in a cross between pelvic-complete (Japanese marine (JAMA) and pelvic-reduced (PAXB) fish, 13). High resolution mapping identified a 124kb minimal interval, containing only the Pitx1 and Histone 2A (H2AFY), genes, which showed perfect concordance between PAXB alleles and absence of the pelvis"
The attached picture is the accompanying figure, where part A refers to this experiment and part B refers to a promoter bashing experiment later.
I have no idea what it means to "look for the smallest chromosome region co-segregating with bilateral absence of pelvic structures in a cross between pelvic complete and pelvic reduced fish". I assumed they did at QTL mapping, but spines appear to be a mendelian trait. Since QTL mapping is done on polygenic traits, it wouldn't work.
Could anyone shed some light on this experiment?

It's captioned: "(A) VISTA/mLAGAN alignment of Pitx1 candidate region from pelvic-complete stickleback (SALR), medaka and zebrafish. Red peaks, >40% sequence identity in 20bp sliding windows; grey bars at top, repetitive sequence; An external file that holds a picture, illustration, etc.
Object name is nihms-215525-ig0003.jpg symbols, microsatellite markers ..."

Providing a link to the full text of the paper would be extraordinarily helpful...


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How would a different solar day affect evolution?
Has anyone theorized how evolution would be affected by a different length of solar day, what were the conclusions?
The thought came from thinking about life on other planets/moons, but I'm initially thinking about it from the frame of "How would life on earth and humans specifically have evolved (or if they would have) if a day were 12 hours or 48 hours?
I imagine the actual effects on evolution and lifestyle would be extensive.
Note: this question How would the human body adjust to sleep times if we were to live in a place with different day lengths? is slightly related, but just to clarify I'm intersted in effect on evolution, not adaptation if an indivdual moved between planets.

Think about places like the arctic circle where there are extended periods of light and dark - that would give some idea. Many plants and animals cope well with long periods of dark, and make use of the co-occurring long days at other times of the year.

True, but I think season variation relates to a different set of effects.  I think things like the study of deep sea life is probably more closely related, just not easily extrapolated humans.

Deep sea is another - seasonally long days and nights were just a starting point for some ideas

its all about adaptation.. we might look different or we might not.. each stage of evolution is basically adapting to changes in the environment to better suit our needs..

This question is a little broad- if you remove the evolution from the question then this is quite answerable.

It depends on how different. Day length affects more than just how long the periods of light and dark are. Let's assume a very slow rotation, and a very long day, maybe 1 month light, 1 month dark. The light side would get much warmer while the dark side would get much cooler. At the border between light and dark sides, you'd expect to see powerful storms as the hot moist expanding air moved into the cooler side and had to lose moisture. Any life on a planet like this would have to adapt to surviving in both hotter and cooler temperatures. We can take this to an even worse extreme and look at a planet like uranus. Uranus's axis is tilted at 97.7 degrees, so even though it rotates, the day/night cycle is controlled by it's rotation around the sun. If the earth were tilted like this, then we would 6 months of light followed by 6 months of darkness. Life would either have to keep moving to stay in the moving temperate twilight zones or adapt to hibernate.
If we assumed a shorter day/night cycle, I think the changes would be less significant. Lets say we had a 4 hour day. ( There has to be a speed where things get thrown off the planet, but I don't think 4 hours per day is fast enough ) A 4 hour day would have 2 hours of light with 2 hours of dark. My guess is that circadian rhythms would be less important. Temperature changes from light to dark would be less significant than currently.
It's an interesting thing to think about because the Earth's day is slowly getting longer as the moon exerts a tidal force on our planet, slowing our rotation and escaping further into space, but this change is so slow I doubt it will ever become a problem for humans.

This answer is good, but you're focusing a lot on how the solar day would affect the environment rather than evolution of humans... or at least not extending those thoughts into evolution.  Would we eat differently? forage differently? have different physical body types..

If it were bad enough we wouldn't be humans. If we had 6 months of darkness and 6 months of light almost every form of life would have to go dormant for half the year, and I don't think humans would develop in an environment like that.

It's an interesting thought, but animals that hibernate (bears / squirrels) are not significantly different from their non-hibernating brethren.

I don't know how cold the dark side of the planet would get, but I'm pretty sure it would be far colder than any winter bears have hibernated through. Wikipedia claims that the polar night lasts about 28 days http://en.wikipedia.org/wiki/Polar_night , which is far shorter than 6 months. And the poles would receive heat from the rest of the planet. If half the planet were dark at any given time, the center of that darkness would get very cold. And while some plants keep photosynthesizing all winter ( conifers ) they only deal with normal nights. 6 months of darkness would challenge them.


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Why are X-linked illnesses less common in females if females have X-chromosome inactivation anyway?
I have read this post but am still slightly confused about this. Do tissues in the human body not all develop from the same cell(s) in the embryo? If so, I do not see how the cell 'mosaic' would be grainy enough to mask the fact that half of the female's cells are not working properly. For example, all liver cells come from the same cell in the embryo which has an inactivated X. In that case, there is a 50% chance that the females liver is dysfunctional. So I would predict that some females would exhibit X-linked disorers even if they are heterozygous, but I haven't heard of this being the case...

think of a given organ in your body (if you're a female) like a calico cat's pattern

Barr bodies (X-chromosome inactivation) don't form in the initial fertilized embryo — it's not that one X-chromosome is inactivated, and then that same inactivation is passed down to daughter cells. Rather, X-chromosome inactivation occurs on a cell-by-cell basis in differentiated cells.  Note how the accepted answer to the question you linked mentions that different cell lineages will have different X-chromosome inactivation patterns — in other words, inactivation occurs later in the differentiation and proliferation processes than I think you might be assuming.
To use your example: the liver cells do not all derive from a pluripotent (undifferentiated) cell with one inactivated X-chromosome, but instead derive from said pluripotent cell, and then undergo X-chromosome inactivation.
Although the jury is out, scientifically speaking, on the mechanisms of selection of the X-chromosome to be inactivated, it's been postulated that some sort of decision-making may occur on this cellular level, resulting in a higher likelihood of inactivating the damaged or deleterious chromosome, if one is present.
Regardless, as the accepted answer to the question you linked mentions, the 50% of functional cells that would result from chance or random X-chromosome inactivation tends to be sufficient for the body's needs.

Let me know if this answers your question!

"the 50% of functional cells that would result from ... random X-chromosome inactivation tends to be sufficient for the body's needs." Does this mean that it is the percentage of functional cells that determines the phenotype of a female? eg if a haemophilia carrier has 50:50 normal:diseased X, they may be fine, but if they had 30:70 normal:diseased X, then they would have haemophilia? Otherwise how do you explain women also get X-linked diseases when one of their X is inactive? Inactivation means only 1 X is meaningfully functional so isn't that the same as males having has just 1 X anyway?


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Redox potentials in photosynthesis light dependent stage
In my lecture notes, it states

...there is a significant thermodynamic problem due to the respective redox potentials of the half reactions:
H2O<--> 1/2 O2 + 2H+ +2e-      pE=+0.82V
NADP+ +2H+ +2e- <--> NADPH +H+      pE=-0.32V

Could someone please explain what the 'pE' is? I thought it would be just ordinary redox potential, however the redox potential for water is apparently +1.23V not 0.82V. I cannot find anywhere a source stating the figures given above or what they mean (I have also consulted Biochemisty, Stryer et al)
Could it have something to do with this being the potential in the conditions present in a typical chloroplast as opposed to standard conditions?

You are right about the conditions in the chloroplast stroma vs. standard conditions. The pH is high (i.e., low H+) in the chloroplast compartment where the reaction takes place (within the stroma), so the pE is shifted from the nominal "pE0", which is +1.23V (effectively you push the equation to the right by low concentration of H+).
See this for a textbook-like summary of the important reactions and this for a quick problem on the math behind pE in different conditions, as well as this for more on the stroma.


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Transmembrane protein: does signal peptide always form a loop?
So I have read a few times that

b. SP probably forms loop not arrow. Loop enters channel (translocon) in membrane. SP loop is probably what opens (gates) the channel on the cytoplasmic side.

Source
And I was wondering why this would be the case? It seems much more complicated to me for the protein to loop around than fior the signal peptide to just embed itself in the translocator pore and the rest of the polypeptide chain be synthesised in the cytoplasmic side.
Then if the protein was meant to pass through the membrane again, there wold be another start-transfer signal sequence (so the two first signal sequences would be two start-transfer sequences rather than a start transfer and a stop transfer).

I think perhaps a picture might help, also see some lecture notes here, where I pulled the pictures from: in short, if you have an unbroken chain, you can't stick it through a hole except as a loop unless you start at the very end, and often you don't want to do that.
Signal sequences can be anywhere on the protein. That portion is the part of the peptide that binds to the translocator pore in the membrane. That portion has to stay bound for the process to continue: it isn't possible to just "feed through" the growing polypeptide without securing it somehow, and that's precisely what the signal sequence is doing by interacting with the translocon.

http://web.uconn.edu/mcb380/fig12-45a.GIF

http://web.uconn.edu/mcb380/fig12-45b.GIF
This process also allows for all sorts of arrangements: sending the whole protein through, or just the N- or C- end, or having multiple signal sequences to create multiple transmembrane domains. Especially in the latter case, there really isn't any other way to do it except by forming some loop someplace, unless you were to actually ligate separate polypeptides together, which would be quite messy and difficult and require additional specialized enzymes: much more complicated than a nice, tidy loop.


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What risk does the insulin pump hack carry?
Recently, a OneTouch system was hacked, potentially allowing any malicious attacks, draining the pump into someone's bloodstream:

Jay Radcliffe, a diabetic and researcher with cyber security firm Rapid7 Inc, said he had identified ways for a hacker to spoof communications between the remote control and the OneTouch Ping insulin pump, potentially forcing it to deliver unauthorized insulin injections.

If this threat is real, what is the theoretical worst-case scenario for a patient with one of these insulin pumps? Is this actually directly life-threatening?

Yes. Yes it is.

i would suggest googling: total amount of insulin in average device; insulin LD50 for these patients. Should help answering the question.


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ADCs: by what mechanism are antibodies internalised
I read that ADCs (Antibody-Drug Conjugates) act by a -mab for a particular target being bonded to a cytotoxic compound. From my high-school-with-crayons knowledge of antibodies, however, one part of the mechanism stands out as being strange: the internalisaiton of the complex into the cell.
In my head, antibodies are either free in plasma or expressed bound to the surface of cells. How and why (mechanistically/evolutionarily/functionally) does this antibody internalisation take place? Is it a natural process in most organisms, or a backdoor which must be engineered into the ADC?
The usual sources for neophytes are quiet in this area, and the advanced material is bewildering.

It's a natural process, endocytosis, but endocytosis is also very complex. If you can gain access, really good article, but some general conclusions: "There are many distinct endocytic pathways that coexist in mammalian cells. Although some cargoes enter exclusively by one pathway, most cargoes can enter by several pathways. Any endocytic mechanism requires the coordinated action of proteins and lipids. The best-understood mechanism is clathrin-mediated endocytosis"

This is actually an extremely broad question, which is why I have voted to close. As @Kendall indicates, the primary (but not only) method of antibody internalization is endocytosis, but there are multiple different forms, and the exact mechanism will depend on the structure of the Ab, its target, where it binds, and the physiological context (normal vs. cancerous cells, etc.). The Annual Reviews article linked might be a little above your head (if you can get access to it), so I'd start with the wiki article I linked, as well as google searches.

Actually, knowledge that the process is called endocytosis helped me greatly in searching, and I've learnt a lot about the process today. I'll take a look at the review article tomorrow. I think it likely that this question with an answer along the lines of the comments above would help a fair few people, but vote as you will to make the place as it should be.

@Kendall perhaps you can add a bit on Fc receptors and convert your comment to an answer.

What we're basically looking at with ADC internalization

Courtesy of Bayer
So the way an ADC works: The antibody-drug conugate binds to a target antigen like a transmembrane receptor, the cell in response engulfs the entire complex and send it to an endosome. What the cell can do with the endosome depends on the cargo. Digressing, the ADC internalization mechanism is often attributed to receptor-mediated endocytosis, where the most prominent mechanism of receptor internalization is the clathrin-mediated pathway. We're going to be referring here most of the time.

Clathrin-mediated endocytosis commences with the recruitment of adaptor proteins, accessory proteins and a clathrin polymeric lattice to phosphatidylinositol-4,5-bisphosphate-enriched plasma membrane regions

A common adaptor protein here is AP2 that's capable of binding to motifs present on the cytoplasmic tails of membrane receptors. What it's doing is selecting which receptors are the cargo. Then the clathrin mobilizes to the now-enriched membrane regions, and the polymerization of clathrin causes the membrane to displace and curve. Dynamins, large helical GTPase proteins capable of stretching the invagination in the membrane to a vesicle, bind the phosphatidylinositol-4,5-bisphosphates in the membrane, and may work in concert with BAR domain-containing proteins and actin tension to stretch the membrane into a vesicle and cut it away (Doherty & McMahon, 2009).
Obviously there's some missing information, as we don't fully understand it. I think reading the first reference, published in mAbs in 2013, is a really good place to start however!


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Can tubular secretion regarded as local hormone?
Tubular secretion is : The process in which ions and other waste products are transported into the distal tubules of the nephron.
can it be regarded as local hormone??

First of all, I can't understand how can you regard an electrochemical process (tubular secretion) as chemical substance (hormone).
Tubular secretion is the transfer of materials from peritubular capillaries to renal tubular lumen. Tubular secretion is caused mainly by active transport.
Usually only a few substances are secreted. These substances are present in great excess, or are natural poisons. Many drugs are eliminated by tubular secretion [1].
The substances that are secreted into the tubular fluid (for removal from the body) include [2]:

Potassium ions (K+),
Hydrogen ions (H+),
Ammonium ions (NH4+),
creatinine,
urea,
some hormones, and
some drugs (e.g. penicillin).

Tubular secretion occurs from the epithelial cells that line the renal tubules and collecting ducts [2].
Uptake transporters in the basolateral membrane and export transporters in the luminal membrane of renal tubule cells are involved in tubular secretion of their substrates (organic anion transporters and organic cation transporters - these are transmembrane proteins) [3].
Despite considerable advances in the understanding of basic transport pathways and mechanisms involved in the tubular secretion of organic compounds, there is still relatively little information on the regulation of this transport [4].

References:

Wikipedia contributors, "Renal physiology," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Renal_physiology&oldid=608689347 (accessed June 26, 2014).
http://www.ivy-rose.co.uk/HumanBody/Urinary/Urinary_System_Kidneys_Actions_3.php
Müller F, Fromm MF. Transporter-mediated drug-drug interactions. Pharmacogenomics. 2011 Jul;12(7):1017-37. doi: 10.2217/pgs.11.44. PubMed PMID: 21787191.
Berkhin EB, Humphreys MH. Regulation of renal tubular secretion of organic compounds. Kidney Int. 2001 Jan;59(1):17-30. doi: 10.1046/j.1523-1755.2001.00461.x. PubMed PMID: 11135053.


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In Study from Blue Brain they say position of synapses doesn't change even if they modify neurons, only when they change shape of neuron it changes?
https://medicalxpress.com/news/2012-09-blue-brain-accurately-neurons.html

We could vary density, position, orientation, and none of that changed
  the distribution of positions of the synapses.....
They went on to discover that the synapses positions are only robust
  as long as the morphology of each neuron is slightly different from
  each other, explaining another mystery in the brain – why neurons are
  not all identical in shape

My question is why, and how come? Am I understanding it wrong?

I'm not understanding which part you are confused by, can you try to explain the issue you have?

Ok sorry. If neurons are placed randomly, then their branches would spread differently and where interactions would happen would be different. Yet it says position of synapses / interactions is the same more or less no matter how much they change few factors... just not with shape. changing shape does change positions of interactions

It helps to go to the original article for more guidance:
Hill, S. L., Wang, Y., Riachi, I., Schürmann, F., & Markram, H. (2012). Statistical connectivity provides a sufficient foundation for specific functional connectivity in neocortical neural microcircuits. Proceedings of the National Academy of Sciences, 109(42), E2885-E2894.
The point of this paper is that they are looking at the statistics at which neurons make connections with each other in neocortex. Neocortex is a layered structure, and cells of a particular type are identified by the location of their soma as well as the structure of their dendrites and axons. A layer 2/3 pyramidal cell, for example, has basal dendrites that spread a lot in layer 2/3 and creep into layer 4, and an apical dendrite that extends and branches in layer 1. Therefore, it can potentially receive inputs from any cell that has axons in layers 1 -> 4.
One hypothesis is that the primary determinant of which cell types are connected to which is simply the morphology of each cell type. If one cell Type A has a bunch of dendrites in a given layer, let's say layer 3, and another cell Type B has a bunch of axons in layer 3, they will have a lot of opportunities to contact and make synapses.
A second hypothesis is that cells connect with specialized guidance cues. For example, dendrites of Cell Type A release a peptide BALover that is detected by Cell Type B, and causes Cell Type B's axons to grow toward dendrites of Cell Type A. In this system, you could still get lots of dendrites of Cell A in one layer and lots of axons of Cell B in the same layer, but caused by the specific guidance cues from A->B.
In the second situation, however, we would expect the arrangement of axons and dendrites within that layer to be non-random. That is, we would find processes of B in greatest density nearest to processes of A.
If you labeled a bunch of Cell Type A from one animal, and a bunch of Cell Type B from another animal, and overlay them, they should have just as many contacts as if you labeled Cell Type A and B in the same animal if the connections are random due to morphology. If, however, there are specific guidance cues involved, you would find fewer.
Hill et al. 2012 shows evidence in favor of the first hypothesis: they get about as many contacts if they take cells from two individuals and overlay them. This is what they mean by "random placement": not completely random in all dimensions but rather random within a layer in cortex, as if the cells are taken from two different animals. Certainly guidance cues are still used and are still important for setting up the structure of cortex, but it seems like individual cells are mostly just programmed to take up a certain shape, and that shape determines their rough probability of connections. This is a good thing for the Blue Brain project, because it means that they can use composite data from many animals to establish connectivity patterns.

I completely missed the layers part. Thanks so much.


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"synapses grow closer together in order to decrease the distance", is it true?
Is there a source?
That synapses get physically get close as their interaction increases.
I have also read that where neurons crosses each other they create new neuron, is that true?

What do you mean with interaction? Synaptic mechanisms? 2. No, as new neurons are born only in restricted areas of the nervous system.

I think you're talking about Hebbian theory? My neuro professor used to summarize this as "Cells that fire together, wire together" (although apparently he was in fact quoting Carla Shatz).

http://www.curiousapes.com/the-science-of-happiness-why-complaining-is-literally-killing-you/

" the synapses grow closer together in order to decrease the distance the electrical charge has to cross. "

The first red flag is that this sentence is incorrect, based on the explanation following it in the source you linked. It suggests that there would be a reduced distance from one synapse to the next, while the text really explains that there will be a reduction in the width of the synaptic cleft. I am not certain enough to give an answer, but the sloppy language alone makes me think the author does not know what he's talking about.


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Is it true reduction in sensitivity to dopamine due to over stimulation from addicting behaviors can be permanent, if yes how come?
I've read somewhat conflicting things.
General concept is this:
Addiction -> Over product of dopamine -> Reduction/Desensitization of dopamine receptors -> problems
And if you let go of addiction you go through period of withdrawl that can last from 90 days to a year.
BUT forever for some people... Why?