Can we say the 'goal' of Mullerian mimicry is a 'decrease in the number of sacrificed indivials'? Can we say that Mullerian mimicry allows two species to decrease their number of sacrifice individuals because:

Originally, one species needs to sacrifice some individuals to allow predators to recognize the warning signals (e.g., 10% of the population);
Another species, with a different set of warning signals, would also need this same population sacrifice (i.e., 10%);
Now, is the benefit of mimicry that, when two species share the same warning signals, each of those two species only loses half of the otherwise sacrificed number of individuals (i.e., 5% in the example)?

What is Müllerian mimicry?

Proposed by Fritz Müller, is when two or more species, which are both unpleasant to eat, poisonous, toxic, harmful etc. have similar colouration and patterns. A key point to note is that they have common (shared) predators. A classic example is the Heliconius genus of butterfly.

Why does it evolve?

The argument you make is kind of along the right lines, but it is a group selection argument, and is worded slightly badly as it insinuates that evolution is a goal driven process. I will use a toy example/thought experiment to explain why it's evolution is adaptive.

In this example there are three species of butterfly are toxic. We will call these species Butterfly-1, Butterfly-2, and Butterfly-3 (yeah, I'm not feeling very creative today). We also have a predator, a bird which likes to eat butterflies. We will call this species Bird.

Butterfly-1 and Butterfly-2 are very different to look at; they have different colours, shapes, and patterns. An individual Bird then eats one of Butterfly-1 and becomes sick. That individual learns to avoid Butterfly-1. Our Bird is then hungry again, and eats Butterfly-2, and again gets sick, and learns to avoid Butterfly-2. Two individuals die before Bird can learn to avoid both species.

Butterfly-1 and Butterfly-3 are very similar in appearance; they have similar colours, shapes, and patterns. An individual Bird then eats one of Butterfly-1 and becomes sick. That individual learns to avoid Butterfly-1, but also to avoid the similar looking species Butterfly-3. Likewise, if it eats a Butterfly-3 then it learns to avoid both Butterfly-1 and Butterfly-3. This is Müllerian mimicry. Survival is higher in one or both species because of more rapid learning by predators, fewer individuals will die compared to the non-mimicry scenario.

The essence of this is captured in the following statement from this paper:

  "Müller provided what could well be the first formal mathematical model to support an evolutionary hypothesis. Following Müller’s original argument (1879), let $a_1$ and $a_2$ be the numbers of two approximately equally unpalatable (or otherwise defended) species in some definite district during one summer, and let $n$ be the number of individuals of each distinct unpalatable species that are killed by predators during a season before their distastefulness is generally known. If the species are distinct in appearance, then each species would lose $n$ individuals in the course of educating predators. If, however, the two species were exactly alike in appearance, then the first species would lose only $a_1n/(a_1+a_2)$ and the second would lose only $a_2n/(a_1+a_2)$. Under these conditions, a mimetic mutant of species 1 that perfectly resembled species 2 would tend to spread from extreme rarity"

Note that there may be caveats and complexities which I haven't discussed, this is a simplification to try and explain the general reasoning


Transcription of Genes: Are Specific Transcription Factors + Enhancers Necessary? I learned about transcription in my AP Biology class and we discussed how transcription occurs, but I was wondering whether transcription always requires the enhancers, activators (specific transcription factors), DNA-bending proteins, etc. to be present, or if this is only used for higher-level production of RNA transcripts?

Can transcription occur if only the RNA Polymerase (I, II, or III) and the General Transcription Factors are present?

Thanks!

enhancers, activators, silencers, repressors are necessary in controlling of the transcriptional process. Utilization of enhancers/silencers plays a part in differentiation of developmental processes (i.e. maturation, growth)

https://en.wikipedia.org/wiki/Enhancer_(genetics)


How can parentage test be accurately done even though crossing over occurs? As crossing over occurs when gametes are secreted, so when a zygote is formed after fertilization, the base pairs of DNA in the child should be different from that of the parents. So when gel electrophoresis occurs, the position of DNA fragments of the child shouldn't be the same as half of their father and mother. But why is this statement wrong? sorry for bad English.

Crossing over is an event that occurs during meiosis, which produces the gametes. This crossing over occurs between 2 homologous chromosomes, which are both from the parent. Hence, even though crossing over occurs, the recombinant chromosome that is passed down to the child will contain an allele that matches with the allele on one of the parent's chromosomes. Within the allele, the base pair sequence would not change.


Chemical structure prediction I'd like to do chemical structure prediction using a known molecule formulas. I'm familiar with de novo protein structure prediction, but are there any programs which will go from formula to structure with optimal geometry of random small chemicals (say 30 atoms)? I found http://cccbdb.nist.gov/mdlmol1.asp but it selects mol files from a limited database. I need a command line UNIX program which computes mols from formulas.

Concise structural formulas popular during past ages are unable to describe every type of chemical structure like morphine. I found no software that supports csf (Smiles and inchi are popular but are encoded and not human readable). When the bonds of the structure are known geometric minimization (DG-AMMOS) orients the structure to a stable native like direction.
http://www.mti.univ-paris-diderot.fr/fr/downloads.html

Did you try to use Bioclipse:

  Bioclipse is mainly based on the Chemistry Development Kit (CDK), and contains a framework for managing and analyzing chemical compounds. Bioclipse supports editing in 2D, processing large collections of molecules in tables, calculation of various types of properties, and much more cheminformatics functionality. The Jmol application is integrated in Bioclipse as an editor, and provides advanced interactive 3D visualizations.


What species is this yellow flower of angiosperm from Morocco? What species is this yellow flower of angiosperm from Morocco? I photographed it in spring. I estimate the diameter of a flower to be 1.5 cm.

It's undoubtedly in the genus Oxalis but there are hundreds of species in this genus.  The genus name refers to the high content of oxalic acid found in this genus.


What is the definition of the life biologically ? I want to know what is the definition of the life biologically , on the other hand ,  what is the definition of the death biologically  ?? However, I think it is a very difficult question to answer .

Could not fit in a comment..

The question is off-topic

Biology is the study of life. Without a good definition of life, Biology itself is poorly defined. It appears that there is no universally accepted definition of life and therefore Biology (just like Chemistry and Physics to cite other examples) is a poorly defined field of study. But it is not scientists job to decide whether their work should stand within one category or another, nor whether those categories are natural categories (see prototype theory) or not. It is the job of philosophers and therefore this question is about philosophy and is off-topic here.

Few notes about the definition of life

Most often, philosophers see a continuum from not living to living things and not a clear dichotomy (ref.).

Biologists, most often just assume that bacteria, archea and eukaryotes are living things while viruses, viroids and prions are not living things. This arbitrary dichotomy is based on the concept of metabolism. However, this dichotomy can lead to some limit cases. Typically, considering viruses as not being living things yields to intuitive issues when thinking about macroviruses such as Marseillovirus and Lausanevirus.

There are two questions in your post

Of course, the definition of what is dead is a total different question from the question of what is a living thing. A stone is not dead it is just not a living thing. Even then, the definition of death is of interest to philosophers, not to biologists. You should always try to limit your post to a single question.


Why do people sleep with their eyes open? It's a fact that some people sleep with their eyes open, but why does that happen? Is it normal behavior, not a symptom of any sort of disorder? Are there any (dis)advantages to sleeping with eyes open?

The medical term is "lagophthalmos" if the person is unable to close their eyes at night.

There are several factors involved, and unless it's due to physical obstruction, lid archetecture (such as short lid length (due to surgery etc)), or facial nerve (CN VII) problems, it's not well understood.

I have seen numerous people with varying degrees of this over the years.  For most of those people, it's an intermittent thing.

Tears are essential for eye tissue health, including cleaning and avoiding infection. People complain of dry or irritated eyes mostly.  But in more extensive cases, keratitis and ulcers can occur, which are bad.  If it's frequent, tell the person to make sure they tell their eye doctor (or if they don't have one, get it checked out sometime) so that the health of their eye tissue can be evaluated.

Another possibility is Grave's disease - in that condition, the entire eyeball protrudes and sometimes the eyelids aren't long enough to cover them adequately.  But what you're describing is probably not Grave's disease.

Wikipedia

American Academy of Ophthalmology


How are single-stranded binding proteins removed from the lagging strand during DNA replication? The lagging strand, downstream of the Okazaki fragment, is covered in single-stranded binding proteins (SSBPs) during DNA replication. What is the mechanism which ensures that SSBPs are removed from the lagging strand to allow for the binding of the next Okazaki fragment?

Actually, there has been some evidence that the SSBPs keep the bases facing outwards so DNA polymerase can still replicate the lagging strand with the SSBPs on them. There has also been other evidence that they can pop off spontaneously.

You can learn more about this by watching the lectures on https://www.edx.org/course/molecular-biology-part-1-dna-replication-and-repair


What would happen if we place denatured DNA in acidic medium? DNA can be denatured at high temperatures or in alkaline solutions. But DNA can be annealed at low temperatures. I want to ask, could it be annealed in acidic medium?

Hello and welcome Nandini Yadav,
It is worth mentioning DNA is an acid (Deoxyribonucleic acid) and intracellular pH is most commonly between 7.0 and 7.4.
Alkaline reagent Example

"The sodium hydroxide (NaOH) is a commonly used reagent to denature the DNA by increasing the pH. At an alkaline pH, OH- groups are predominant. They remove the hydrogen- bonds-contributing protons from guanine and thymine, thus breaking the hydrogen bonds between the two oligonucleotides."

Source
You can see in the image below hydrogen bonds between nucleotides Adenine (A), Cytosine (C), Guanine (G) and Thymine (T).

Acid reagent Example

A decrease in the pH was found to deteriorate the thermal stability of DNA

Source
At an acidic pH, the H+ in the surrounding environment of DNA is high and therefore the hydrogen bonds between Adenine (A) and Thymine (T), Cytosine (C) - Guanine (G) will 'break'.
More information here.


Does the use of RNA as a primer affect the accuracy of DNA replication in E.coli? DNA polymerases have proof-reading ability, but RNA polymerase does not. Does the use of RNA as a primer affect the accuracy of DNA replication in E.coli? Explain

E.coli use DNA polymerase for DNA replication too. Primase creates a short oligonucleotid (primer) in the start of string and DNA polymerase continues in work. RNA polymerase is using in synthesis of RNA molecules.


Gene silencing: relative or absolute number of methylated CpG sites? CpG content varies a lot across the human genome. What does determine a promoter to be silenced through DNA methylation: the fraction of CpG sites that are methylated or the total number of methylated CpG sites? Any reference?

Generally, robust silencing by DNA methylation requires that all or most CG sites be methylated and that there are a good number of CG sites to methylate.  (A 'good number' is relative to each species depending on CG content of the respective genome.)

A promoter with ~10% of its CG sites methylated would not likely be silenced.  However, the caveat with this is that one well-placed methylated CG can cause silencing or at least decreased promoter efficiency.  Also, many promoters are depleted for CG, which means they can be fully methylated, but still not have much absolute methylation.  These promoters can be active despite apparent 'hypermethylation' in the CG context.  Also, a caveat to this is that promoters with zero methylation can be silenced, even if they have CG sites.  Basically, if CG methylation is important in the regulation of a gene, it will have CG sites in functionally-important parts of the promoter.  The promoter will be well-methylated when the gene is silenced, but because placement of de novo CG methylation is not absolutely perfect, there is a high likelihood that there will be more methylation than is needed for silencing to be achieved.  A sort of overkill phenotype.

This paper from the Schubeler lab is a nice foray into the mammalian promoters, which they break into 3 different groups depending on CpG content, and then further analyze each group for CG methylation profiles.


Steps to confirm if predicted miRNA is good or bad I aligned all miRNAs available to the supercontigs of a particular genome with certain parameters (e value of 0.01 and a word match of atleast 7 as suggested in this paper). I have also isolated the pre-miRNAs (+100 nucleotides from either end of the match area). What would you suggest as ideal ab-initio methods to confirm that these miRNAs do exist in that particular genome? Some papers I found use mFOLD like this.

What would you suggest as best steps to confirm if a predicted miRNA/pre-miRNA is really present in the genome.

There won't be any duplicates in miRBase (for a given organism). Choose the taxon nearest to your organism if you are doing homology based discovery. If you want to take all/many organisms then you can use fastx_collapser to collapse redundant sequences. However you will lose the name of the miRNA. You can use awk also for this and it will keep the sequence header from the first organism in the list.

awk '/>/{$0=h} !(/>/){if($0 in a){next} else{a[$0];print h"\n"$0}}' organism1.fa organism2.fa ... organismN.fa

Make sure that there are no extra newlines, otherwise you might need a small modification

To know if something is an expressed miRNA you would need to do a small RNA sequencing. There are some tools like mirdeep and mirSVR which you can use to discover miRNA sequences.


Why are new vessels more permeable in microvasculature? I know for microvasculature

  New microvasculature (arterioles, venules) are always more permeable
  as they lack pericytes.

and then I have this sentence about new blood vessels (not specific)

  New vessels contain initially only proliferative endothelium, the basement membrane has not formed yet, and pericytes are absent.

However, I think pericytes are only around microvasculature.

I think the second statement is correct for microvasculature too.

Why are new vessels more permeable in microasculature?

In adult/pediatric humans, no they don't.  A good figure to get everyone on the same page was made by Cleaver & Melton:

It is important to note that:

  In fact, endothelial diversity is reflected by vessel size-specific,
  organ-specific and even age-specific differences. (1)

Developing blood vessels in the fetus can be a bit of a different story, and highlights the fact the one should loose the "inert plumbing" mentality of the previous century.  Modern research tells us that the epithelium is a very dynamic region that participates heavily with signalling.

When large vessels are growing the fetus, mesenchymal stem cells and neural crest cells are the normal precursors to pericytes, but depending on exposure the line between pericyte and smooth-muscle cell can be blurred (2).  I'm assuming it's beyond the scope of the answer to go into the signalling differences.

A good review of endothelium generation, and the surrounding tissue, can be found here.


What would need to be discovered to prove there is extraterrestrial life? Curiosity is on the Martian surface and is equipped with a slew of laboratory equipment. What would Curiosity need to discover to prove there is or has been life on Mars? Would it have to find DNA (or its Martian equivalent)?

Curiosity is on the Martian surface and is equipped with a slew of laboratory equipment.

But not, incidentally, equipment to detect life.

  What would Curiosity need to discover to prove there is or has been life on Mars? Would it have to find DNA …?

No. In fact, DNA would be lousy evidence of life on Mars, it would almost certainly be a contamination from Earth.

Lacking equipment, I’m not even sure how Curiosity would go about finding traces of DNA but assuming that it did (through some sort of chemical assay), it has no way of telling the origin of said DNA.

And even if the genetic material could be sequenced there are a number of scenarios. It could be very similar to what is found in extremophiles on Earth, in which case we wouldn’t necessarily know the origin (but due to the aforementioned contamination risk, the prior probability of it being Earth life would be very high). If it were completely different, that might be compelling enough to consider it extraterrestrial.

But maybe not: estimates for the number of existing species on Earth vary drastically. One thing is certain, though: we’ve only scratched the surface of prokaryotic life in particular. So if we find something new, that wouldn’t even be very surprising.

More interesting would be an alternative genetic material, neither DNA nor RNA. So far, we haven’t discovered anything like this on Earth (despite earlier hopes) so it would be more likely of extraterrestrial origin. But again, as the refuted study shows, we cannot entirely exclude the possibility of such life being found on Earth either.

All this is just to show that proving microbial life to be extraterrestrial is quite hard. It would be much easier if we were to find non-microbial life on Mars (i.e. something multicellular). However, I don’t know of any serious scientist who seriously entertains this possibility.

But the reason to prefer such a discovery is simple: the bigger the life form, the less likely that we haven’t found it yet on Earth, and the smaller its viable niche. So if we find multicellular life adapted to the surface of Mars there aren’t many places on Earth where it could have originated from, never mind the low chance of having survived the ride aboard the probe.


Book recommendation: Modern Synthetic theory I'm a zoology minor. I wish to study modern synthetic theory (evolution) is there a good book available online for reading?
The book should cover a basic idea about what the elements of modern synthetic theory are and briefly what are the conclusions of the theory.

Feel free to suggest edits.

There is no modern book of evolutionary biology that is not about the modern synthesis. So what you are looking for is just an introductory book to evolutionary biology.

I think the 2 most common introductory textbook to evolutionary biology are:

"Evolution: Making Sense of Life" by Carl Zimmer
"Evolution" by Futuyma

Note by the way that one can find recommendation on population genetics (subfield of evolution) here.


Do viruses linger/passively transport or attack the body at once? Do viruses generally attack as soon as they can or do they lie dormant until they reach a cozy spot in the body?

Like is it improbable I have inhaled a virus if I do not feel pain in my lungs?

Different viruses have different "modes of attack". Also, it depends on what you mean with "attack".

As a really short introduction to what viruses are, they are very unlike your body cells or bacteria. They are literally (usually) just genetic information with a kind of shell. The shell allows them to penetrate cells, where they then use the cell itself to produce more viruses. That's all they do, reproduce.

So, what do I mean with different "modes of attack" - well, different viruses lead to different things. For example, infections with Herpes simplex are often asymptotic and many people have no idea that they are infected. If you get the flu, however, you will notice.

Every virus that can infect humans will try to spread as soon as it enters the body. It won't linger around and wait - HIV directly targets immune cells, herpes directly targets nerve cells. The reproduction does takes time, but if they start reproducing and the immune system can't destroy them immediately symptoms can follow soon (think influenza) or late (HIV/AIDS). With most viral infections, the immune system at one point catches up and destroys the virus.

  Like is it improbable I have inhaled a virus if I do not feel pain in my lungs?

I'm going to assume you mean either the virus responsible for colds (rhinovirus) or the flu (influenza) here. No, it's perfectly normal to be exposed to either of these viruses without noticing anything. Many people come into contact with infected people without ever showing any symptoms, because their immune system takes care of the infection before any symptoms show up. If it does show up, it will be within a matter of days, though. The flu virus won't stay in your lungs for weeks waiting, it has no way of doing that (viruses are... very simple in that regard).


At what point do scientists consider something sentient vs random and/or genetic? When I was thinking about sentience from a scientific point of view, I was confused about the bio-electric mental difference between a paramecium, dog, human, and supercomputer.

At what point does electricity go from being random and genetic to creating logic gates for perceived "sentience" / intelligence?

if you have 300 neurons and 10 of them can put you in a depressed state, you are a sad eukariote.

To compare the logic gates of a worm and a mouse? which one is sentient? a slug literally has 10k neurons and a fly has 250k. that would make a slug 25 time sless sentient than a human, and a dog less sentient than a human, but a human is equally as sentient as a dog so numerically there may be now lower bounds.

Logic Gates are electronic switches which provide routing for AND/OR/NOT/EQUALS of data types, or objects. They come into existence when you have the first cilia and sensory cells. 20 nerves are a signal routing engine, logic system.

A neuron can roughly represented by 4-8 transistors, and a logic gate is a simple transistor routing/instruction, so a worm has about 2000 logic gate equivalents. https://en.wikipedia.org/wiki/List_of_animals_by_number_of_neurons

A logic gate is digital, a brain is analogue, no software, , so you inadvertantly weave smoke and mirrors to clarify your question.

The question evokes electrical sentience, synapses are electrochemical, slower than electricity and can varied in many ways chemically, and they are self organizing.

feeling, aware and knowing (reductionism of sentience) are much more debated topics in science. Relative to random and genetic logic gates for intelligence, that's unclear and you are discussing free will and decision (philosophy), intelligence has unclear relation to sentience/emotion.

Your question is confusing a vast range of scientific measures by using the term sentience, which is rarely used in science. Scientists write informally about sentience as an ethical issue based on their experience, but there's only fringe research on animal sentience. https://scholar.google.fr/scholar?hl=en&as_sdt=0%2C5&q=sentience+fish&btnG=

Animal psychology is a scientific topic, and sentience is metaphysical, it means feeling, aware and knowing, it's incommensurate and imprecise.

So scientists don't consider there to be such a point of sentience. They measure certain markers of sentience, such as

self awareness,

stress response,

emotional queues,

counting,

comparing,

memory,

puzzle solving,

social behaviour,

hormones, that kind of thing.

There are perhaps a 2 publications about sentience in fish, none about lizards or insects, and there are thousands of books and opinions about sentience in insects and other animals.

The brain increases in size from a dozens to billions of neurons. So the progression is in stages, so awareness is likely to be a complex series of steps.

A good animal psychologist can give you an entire book about the onsent of emotions and knowing in animals.


Can cats use ketone bodies as only source of energy? I recall reading that much of the energy a cat produces from its food comes from proteins which I assume would produce energy via being catabolised into amino acids which in turn, if glucogenic, would undergo gluconeogenesis and then, by means of being metabolised into glucose, enter glycolysis and the resulting pyruvate would be converted to acetyl-CoA and enter the TCA cycle to produce energy. I'm wondering whether this recollection is accurate and whether cats could, like humans, use ketone bodies for their sole fuel source if need be.

You are correct that cats consume a lot of protein, and it's safe to assume a large share of this is broken down to amino acids, which are then oxidized to produce energy. But amino acids in general are not catabolized via glucose; instead, they are converted into compounds that feed into the TCA cycle via other biochemical routes.

Almost every of the 20 proteinogenic amino acids have their own specialized catabolism pathway, so this is a large topic. The general theme is that the amine nitrogen is first removed by a transaminase to yield a keto-acid, which is when converted into a carbohydrate that can enter the TCA cycle. To give but one example, leucine is converted in the mitochondrion by a series of CoA-coupled intermediates into acetyl-CoA and acetoacetate (a ketone body; see below). The acetoacetate in turn yields two more acetyl-CoA. A description of this pathway is found at the HumanCyc database. This is a great resource for learning amino acid (and other) biochemical pathways, and provides literature references.

Some amino acids are indeed used for gluconeogenesis, mainly by the liver, but this is not a requirement for their catabolism by most tissues. (It would be energetically inefficient to first generate glucose and then break it down again!) An exception is the central nervous system, which does require glucose and cannot subsist on fat or amino acids (for reasons that, to my knowledge, are still not well understood). So in order to support the CNS on amino acids, the route your describe via gluconeogenesis does occur.

Ketone bodies (acetone, acetoacetate and beta-hydroxybutyrate) are the main alternatives to glucose accepted by the CNS. Gluconeogenesis is energetically expensive in the long run, and if deprived of dietary sugar for a long time, the body will increase its usage of ketone bodies instead of glucose. However, ketone bodies can never fully replace glucose: even during prolonged starvation in humans, blood glucose is kept > 2mM. The CNS would not function otherwise. I'm not an expert in cat physiology but I would bet the situation is similar.


Bug ID? Lower New York Found it on the floor of my basement laundry room in a mostly wooden house in the woods in Westchester County, NY. However I had done a mountain hike (same general area) and I may have brought it from there on my pants or something, but I'm not sure.

When it noticed me it stopped moving, but it was still alive because when I put it in this cup for a pic I accidentally flipped it upside down and it started squirming to get itself upright.

That's not an insect but a crustacean (it has more than 6 legs).

It is a woodlouse (plural woodlice). A woodlouse is one of the few terrestrial isopode crustacean. There are about 5000 known species of woodlice. I have no idea which one is the one you captured!

Woodlice are generally appreciated in gardens as they control pests. They sometimes get inside searching for moisture. While it may not be pleasant to have woodlice at home (just because they look disgusting to many, me including), they do not spread disease or cause much damage.


Similarity between the human genome and archea genome in deep sea hydrothermal vents? I'm trying to find some reference that shows what percentage of the human genome is similar to some organism from the domain Archea that lives  near or on deep sea hydrothermal vents.

Can someone points me out in the right direction?

To achieve whole genome alignment between a genome as large as a human, and as small as an archea organism, is possible, but in the end, you'll have to strain your eyes to see patterns. The archea genome is about 1-5 million bp long, whereas the human genome is about 3.3 billion bp long (that's a thousand times too large).

In practice what this means is that you may or may not have small islands of similarity, in vast regions of emptiness.

Nevertheless, you can align whole genomes using the MUMer tool (http://mummer.sourceforge.net/). The white paper is here
Delcher, Arthur L., et al. "Alignment of whole genomes." Nucleic acids research 27.11 (1999): 2369-2376.

You might also be interested in reading this:

Wei, Liping, et al. "Comparative genomics approaches to study organism similarities and differences." Journal of biomedical informatics 35.2 (2002): 142-150.


What kind of tree is this? I live in Denmark, Europe and was going for a walk on a beautiful cemetary in the city. I saw this tree and would like to know what species it is.

Unfortunately i have no photos of the tree from a closer distance.

This is a Birch tree, Betula sp., probably B. pendula, a common species in Denmark that also has hanging branches. It can be identified by the white bark and the leaves, that are not as long as a willow.


Recommended sequence clustering algorithm for transcriptome data I'm working on a project where I'm going to analyze a large amount of transcriptome data. After assembling our RNA-Seq reads into contigs using Trinity, it looks like I'm going to have about 10GB of sequences in fasta format. Since these sequences are from several hundred tissue libraries but from a single species (chicken), I'm expecting there to be a lot of redundancy, so I'd like to cluster these sequences and just use a representative sequence from each cluster as I go forward with my analysis. I see there are quite a few tools that exist to do things like this, and I'm wondering which you all would recommend. I'll be running this on a Linux machine with 64 CPU cores and ~500GB of RAM.

I started looking at USEARCH, but it seems I'm going to run into some memory issues with the free 32-bit version and as much as I clicked around on their site I couldn't figure out how much the 64-bit version costs or how to buy it.

It does sound like you have a lot of data.

I would first try Robert Edgar's other newer tool UPARSE which is faster and can handle more data using the free 32-bit version.  I think you'll mainly be limited by machine memory though, right?

Did you try CD-Hit?


What will happen if there is high concentration of both calcitonin and PTH in blood? What will happen if there were a high concentration of both calcitonin and PTH (parathyroid hormone) in the blood? In that case, will calcium resorption from bone occur, or absorption from intestine, or deposition of calcium in bones? Also, will blood calcium level rise or fall?

Short Answer: quite surprisingly, both will occur.

Long Answer: as is quite well known, calcitonin lowers blood Ca2+ levels. It performs this task by two methods:

it inhibits the activity of osteoclasts in the bones (Custoff, 2008)
it inhibits reabsorption of Ca2+ in renal tubular cells, allowing it to be excreted in urine (Potts et al, 2008)

However, the second mechanism is only minor. On the other hand, parathyroid hormone (PTH) performs just its opposite: it increases Ca2+ levels in the blood.

So, lets come to the main point: since calcitonin and PTH have opposing functions, what would happen if both were acting simultaneously?

It seems, funnily though, that both the functions will occur simultaneously. Wong et al, 1975, in their research, showed that the target cells of calcitonin and PTH are different i.e. calcitonin and PTH act on different osteoclasts. So, to put it simply, while activity of some osteoclasts would be decreased, that of some others would be increased. Overall, Ca2+ levels in the blood would remain pretty much constant.


Sitting in a closed room filled with regular air - for how long will the air last? The question has implicitely a lot of variables attached to it:

volume of the room
activity
how closed the room is
size of the person (I'm 168cm long and 64 kg heavy)

That could probably be turned into some formula and I am interested in scientific insights.

But at the end of the day my question is actually of very practical nature. I have a small room - about 1m x 2m x 2.5m = 5m3 - and I would like to use it as super-quiet place for meditation, reading etc. - hence calm activities, no excessive moving around. To improve sound proofness I'll probably also increase the sealing of the door and there is no ventilation - no air exchange.

Now if I close the door - how long can I expect to stay there without the air quality deteriorating to a level where my mental processes start to be impaired by it?

Since you are considering to meditate in the room, without any excess of activity, you can consider the average resting O2 consumption, which is C = 3.5 mL/(min.kg) [1].

If we ignore the volume of your body, initially the room is filled with VO2(t0) = 0.21 * 5 = 1.05 m3 of O2.

With you breathing in the room, you can consider the volume of O2 in the room as a function of the time:
VO2(t) = VO2(t0) - C * M * t
where M is your weight in kg, and where C is converted to m3/(min.kg).

An oxygen defficient atmosphere is an atmosphere for which oxigen content is below 19.5 % of the volume [2]. An oxygen defficient atmosphere can be dangerous for your health. So in your case you need to find the value of t for which VO2(t) becomes inferior to the threshold Th = 0.195 * 5 = 0.975 m3.

So the maximum time you can spend in your room would be:
tmax = (VO2(t0) - Th)/(C * M) = 335 min = 5 h 36 min

Of course, this value is a bit surestimated, and you should leave the room before that time.

[1]  M. Kwan, J. Woo & T. Kwok (2004) The standard oxygen consumption
value equivalent to one metabolic equivalent (3.5 ml/min/kg) is not appropriate for elderly people, International Journal of Food Sciences and Nutrition, 55:3, 179-182, DOI:10.1080/09637480410001725201

[2] https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=12716


What are in common between transcription factors? In terms of their structures (primary to tertiary) and locations?

Why do they have these commonalities? Or are any of these commonalities critical to their functions?

Transcription factors are a very heterogeneous group of proteins. Their two main objectives are to bind DNA & to recruit polymerase to that site. There are a of ways for them to accomplish these tasks.

To bind DNA, all they need is a pocket of positive charge, which are found in several structural motifs across many proteins. The wikipedia page actually provides a good sample of this diversity: https://en.wikipedia.org/wiki/Transcription_factor#Structural

The other co-factors that transcription factors recruit to get polymerase to the DNA strand also vary pretty widely. They link together through structurally complementary pockets of opposite charge, but beyond that, the details get pretty messy and there are a lot of details. Even reviews of transcription factors tend to focus on a specific class. If you want more than that very simplified explanation, I would actually recommend reading some reviews on the subject. Here are a couple:

http://www.ncbi.nlm.nih.gov/pubmed/25755661

http://www.ncbi.nlm.nih.gov/pubmed/25640595


Is there a practical upper limit to amount of nucleotides or genes in a transformed plasmid? I'm currently working on a synthetic biology project which involves working with lots of different parts. I would ultimately like to integrate these genes by transforming a single plasmid. I've heard (casually) that 9-10 foreign genes on a transformed plasmid is often the practical upper limit for these types of experiments, without a real explanation other than "beyond that, it just doesn't work".

Is there a practical upper limit to size of amount of genes in a transformed plasmid, assuming all need to be expressible? What causes this upper limit?

From my experience in the mammalian world (and this may apply to bacterial systems as well), it's not so much the number of genes in the plasmid as its actual size. The larger the construct is, the more difficult it will be to get it into your target cells in one piece, without degradation or shearing. Since the transformation efficiency is lower, you are getting fewer whole constructs per cell, so depending on how you've set up your promoters, the overall expression level can be significantly lower. The trouble with splitting your genes amongst two or more plasmids is that each will have different transformation efficiencies, and there will be a certain (perhaps large) number of cells that don't get the full complement of genes, interfering with phenotype analysis. And again, you'll also have to consider differential expression rates.

However, once you get your vector into the cells in one piece, theoretically they should all get expressed at approximately equal levels (assuming identical promoters). It's possible that steric hindrance among multiple transcription complexes may occur - I just don't know enough about bacterial transcription and the effects of circular plasmids to say.

One way to get around many of these factors would be to use a bacterial artificial chromosome or BAC. BACs are 7-10 kb vectors that can have inserts of up to 1 million bp cloned into them and are then electroporated into cells. One of (the many) cool things about them is they control their own duplication and partitioning at cell division, so succeeding generations should have essentially the same copy number as the original. They were heavily used during the Human Genome Project to amplify large sections of DNA for sequencing, but they are also used in many other studies, including synthetic biology. OpenWetWare has a list of some common ones, and NEB sells pBeloBAC11 systems.


Sequencing the genomes of polyploid organisms I've done some transcriptomics work in the past with a polyploid organism, and this presented some unique challenges in the data processing and analysis. Since then, I have been brainstorming about the technical challenges one may face when sequencing and assembling the genomes of a polyploid organism. As far as I am aware, there are no polyploids whose genomes have been sequenced.

If one wanted to sequence, for example, a tetraploid organism, one approach would be to prepare and sequence all of the DNA together and then rely on post-sequencing analysis to tease apart the two co-resident genomes. However, it would be difficult, if not impossible, with this approach to distinguish inter-genome variation from intra-genome variation.

An alternative approach would be to isolate DNA from both co-resident genomes separately, and then sequence and assemble the genomes separately, so that inter-genome variation and homology need not be considered. However, I'm thinking at a very high level and have little intuition as to the technical feasibility of this approach. When there are two or more co-resident genomes, is it be possible to isolate DNA from only one of those genomes? What would this rely on (for example, would thorough cytogenetic/cytogenomic characterization help)? If this task is not possible, what types of limitations must be overcome to enable it?

Take a look at the strategies used to sequence the wheat genome. Wheat is hexaploid. The project is described at http://www.wheatgenome.org/.

For early work on the maize genome, we employed methyl filtration in order to reduce genome complexity and size - transposons are filtered out and genes + promoters and such remain. The gene sequences are different from the two genomes, so says the theory, and those can be distinguished. See http://www.ncbi.nlm.nih.gov/pubmed/10545948 for the reference.


When should I use cryofixation and chemical fixation? We know that the technique used in TEM sample preparation involves multiple steps, one of the most important of them is fixation.
Fixation can be of two types:

Cryofixation, that suggests that the specimen are subjected to freezing temperature to perserve the cell's living material before we observe them.

Chemical fixation involves the use of certain chemicals, such as formalin, glutaraldehyde, etc. for almost same purpose.

The question is when it is mandatory to use one of them only? Such as, cryofixation or chemical one? At some instances, have the researchers ever need to use both of the techniques at the same time?

Cryofixation usually preserves the organelles inside the cells better, but is more work and usually results in TEM images that are lower contrast. Chemical fixation is easier and gives good contrast, but is more likely to destroy details in delicate samples. Chemical fixation will usually be used unless it is found or expected to not work well for a particular sample. It is possible to mix the methods, for example by including glutaraldehyde in freeze substitution solutions. Here is an article that describes everything you asked about in more detail, if you can access it: A comparison of cryo- versus chemical fixation in the soil green algae Jaagiella


new DNA sequencing technologies? Last year I did my thesis in the field of a new method for DNA analysis.
Which I think is very interesting although I cannot seem to find any new methods in this field especially the SMRT sequencing method.

Do you maybe know a new method(s) which are introduced for DNA research in the area of SMRT sequencing ?

I don't know, which technique you worked on, but there are the so-called 'Next Generation Sequencing' methods. I think the oldest of that is a pyrosequencing technique called 454 sequencing (I think it is provided by Roche). However, this method is too expensive compared to even newer methods and the support will be stopped within the next months, as far as I know.

Furthermore, there are the Illumina and the ion torrent technique. Finally, there is SMRT sequencing of which some people say that this is even third generation sequencing. I think, this paper provides a nice overview. And if you're interested in further reading, yet you know what to search for.


Difference between Peptone, Peptide and Proteose In my school textbook, it is given that Pepsin converts proteins to peptones, proteose and peptides.

What is the difference between the three products? On googling the terms, the definition was similar.

Peptone: a soluble protein formed in the early stage of protein breakdown during digestion.

Proteose: A proteose is any of various water-soluble compounds that are produced during digestion by the hydrolytic breakdown of proteins short of the amino acid stage.

Peptide: a compound consisting of two or more amino acids linked in a chain, the carboxyl group of each acid being joined to the amino group of the next by a bond of the type -OC-NH-.

Peptide has a different definition, but it can be applied to the other two too as all are degraded proteins but not amino acids.

Quick Answer

Peptide refers to at least two amino acids joined by amide bonds.
Proteoses are products of acid proteolysis which precipitate with saturating ammonium sulfate.
Peptones are products of acid proteolysis which do not precipitate with saturating ammonium sulfate.
While peptide is a term of significant relevance today, proteose and peptone are anachronistic.

Long, Confusing and Out-Dated Details

The terms peptone and proteose were first used in the late 19th century, which makes finding substantive definitions, well, difficult. I refer you to the following paper (yes, 1891...). It is not the first to discuss proteoses, but I can't find any earlier ones and the explanation is quite clear (emphasis added).

Chittenden RH, Hartwell JA. 1891. The Relative Formation of Proteoses and Peptones in Gastric Digestion. J Physiol 12:12-22.

  In the digestion of proteid matter by pepsin-hydrochloric acid there are three well-defined products or classes of products, viz. acid-albumin or syntonin, albumoses or proteoses, and peptones. We look upon the first as the initial product of gastric digestion and identify it by its well known precipitation by neutralization. In the filtrate, the [proteoses] can be detected... best by saturation with ammonium sulphate, while the true peptones... are found in the filtrate from the latter precipitate... True peptones are bodies not precipitated by saturation with ammonium sulphate, and are the final products of pepsin digestion.

NB: proteid = protein

So, according to this paper (and apparently "all physiologists" at the time, see below), there are three main products resulting from pepsin-acid digestion of protein:

syntonin - the initial product, precipitates upon neutralization (likely due to acid denaturation)
proteose - the main product after continued digestion, characterized by precipitation with saturating ammonium sulfate

  Study of the individual proteoses formed in the gastric digestion of albumin, fibrin, globulin, myosin, casein and other proteids has seemingly already shown that these so-called preliminary bodies are the main products of the digestive action of pepsin

peptone - the final product of digestion, does not precipitate with saturating ammonium sulfate

  All physiologists are presumably agreed that peptone is the final product of gastric digestion

They further emphasize that peptone is a product of continued proteose digestion:

  Since the discovery of the [proteoses] and of their characteristics, frequent study of digestive mixtures has given convincing proof that in an ordinary gastric digestion of any common proteid only a comparatively small amount of peptone is formed; peptonization in the true sense of the word results only from the long-continued action of pepsin-acid, and even then complete peptonization rarely if ever occurs. The... proteoses are to be considered as the primary products of gastric digestion, while peptones are the end products of proteolytic action, the latter being formed by the gradual hydration of the primary products...

It would seem that peptone differs from proteose only in the length of its constituent peptides, with peptone containing shorter peptides due to continued proteose digestion. However, a more recent paper (with more recent meaning 1924) challenged this view and claimed that both proteose and peptone consist of small peptides which differ in amino acid composition rather than length. In their view, different composition rather than length explains their differential solubility in saturating ammonium sulfate.

Rudd GV. 1924. Proteoses, Peptones, and Polypeptides. Aust J Exp Biol Med Sci 1:187-190.

  ...each fraction must consist of a mixture of comparatively simple peptides, which differ among themselves in the amino-acid units of which they are constituted. The fact that some, at least, of these peptides are precipitated by ammonium sulphate shows that they belong to the group of proteoses, which therefore are partially, if not entirely, made up of simple peptides.

  It is possible that the terms, "proteose," "peptone," and "polypeptide,*' will all have to be considered to apply to substances of the nature of peptides... each built up of a small number of amino-acid units and differing from each other, not so much in the number of amino-acids in the molecule, but rather in the variety of these acids. The differences in solubility in various solutions shown by these compounds are thus to be attributed to differences in their chemical constitution, rather than in their molecular complexity. If this be so, these substances would be considered, not as successive stages in hydrolysis, but as products of one completed stage, differing in their solubility's.

They also quote another paper with supporting evidence:

  Fischer produced tripeptides and tetrapeptides of known composition and structure, which were precipitated when their aqueous solutions were saturated with ammonium sulphate. If these peptides were found in the solution obtained by the hydrolysis of a protein with pepsin they would be classed as proteoses.

I wasn't able to find any subsequent research. Nevertheless, such definitions from this period are based on macroscopic physical, rather than molecular, properties of the substance. This old terminology is not particularly informative in modern biology, and it would seem that they remain in use only as historic anachronisms. Today, both peptone and proteose are terms used almost exclusively when describing microbiological culture media (which dates from the period) or when making general reference to digestion products. In fact, they are often used in conjunction (ie proteose-peptone) which suggests they are now synonymous.


TRANSFAC Matrix.dat retrieve count matrix using BA or CC field In the TRANSFAC Matrix.dat most of the motifs are given in the form of count matrix, but a few of them are given as some kind of frequency matrix. Those aren't ordinary PWMs because rows don't sum to 1, but these sums are more or less stable across rows.

I would like to have a raw count matrix in all cases, so I trying to retrieve the count matrix from those several "fractional" cases.

At first I thought that the field BA (Basis - statistical basis of the matrix) MANDATORILY starts with a number of sequences actually used in the matrix, so I would be able to simply multiply:

$$
\frac{\text{nucleotide value}}{\text{row sum}} \times
\text{number of sequences from BA}
$$

Moreover, sometimes in CC field there's information like: core from: 11

Unfortunately, the results are not very close to integer value, so this cannot be explained by rounding errors.

For example, in a certain row we have (btw, the row sum is $10.73$ from rounding errors):

3.99   4.07   0.87    1.8

BA  17 compiled ... sequences; total weight of sequences: 10.74

CC  core from: 11, length: 6

$$
\frac{4.07}{10.74} \times 17 = 6.4423
$$

$$
\frac{4.07}{10.74} \times 11 = 4.1685
$$

In my opinion these values $0.44$ or $0.16$ couldn't be explained by rounding errors. There's no description (link to article) enclosed to this motif. That aren't log-odds because all of them are non-negative values.

In this particular case, if I use the formula $count(x) = round( (\frac{x}{10.74}) \times 11 )$, the resulting counts will sum up to $11$, so it's fine.
This method with value $11$ replaced by $17$ doesn't result in set of values summing to $17$, but $16$.

The problem is that in another example I have

BA  17 compiled binding sequences; total weight of equences: 12.86

CC  core from: 1, length: 4
In this case I should rather multiply by $17$ not $1$ to get the sum of $17$.
As you see, I cannot stick to either BA or CC for all such motifs.

How would you retrieve the raw count matrix in a such case and what could be the problem in my approach? (jumping between BA and CC values)

Could anyone explain how those values in matrix have been derived, is it some kind of log-odds?

So databases like TRANSFAC are of somewhat... variable quality. Those matrices maybe have been derived from a program that just doesn't output a count matrix, but instead outputs a frequency matrix directly. What I would do, and what i have seen people do in published papers, is just multiply the matrix by 100 and round down. It's a kludge, but you'd better be quality checking the matrices somehow anyway, otherwise you're going to get 90% crap.


What does it mean to combine in-solution capture of chosen RAD tags to target sequencing reads to desired loci? The article about "rapture sequencing" found
here says:

  "This protocol also recovers more unique (nonclonal) RAD fragments, which improves both standard RAD and Rapture analysis. Rapture then uses an in-solution capture of chosen RAD tags to target sequencing reads to desired loci. Rapture combines the benefits of both RAD and sequence capture, i.e., very inexpensive and rapid library preparation for many individuals as well as high specificity in the number and location of genomic loci analyzed."

My question is regarding the second sentence. What does it mean to combine in-solution capture of chosen RAD tags to target sequencing reads to desired loci? How do the RAD tags target sequencing reads, if that is what is being said here? How does this relate to combining the benefits of both reduced representation sequencing techniques, or am I missing the crux of the paper?

http://www.genetics.org/content/genetics/202/2/389/F1.large.jpg?width=800&height=600&carousel=1

Schematic overview of the new RAD protocol and RAD capture (Rapture) method. (A) RAD tag isolation. Two wells are depicted in each of two different plates. Genomic DNA is digested with a restriction enzyme and ligated to biotinylated well barcode adaptors (yellow and blue bars). (B) RAD tag isolation and library preparation. DNA from each well is pooled platewise, mechanically sheared, and incubated with streptavidin beads. Following washing, DNA is cleaved from the beads leaving the well barcodes. Finally, a library preparation is performed where a unique plate barcode is added (red and purple bars). (C) Rapture. Multiple plate libraries are pooled, hybridized to biotinylated oligonucleotide baits corresponding to the targeted RAD tag loci, and captured to produce the final library enriched for the loci of interest.


Essential fatty acids function Why are essential fatty acids so essential? I know that if taken less then it would cause diseases, but what metabolic role do they play? Are their importance is just because of their structural role?

Essential fatty acids consist of two main EFAs - Omega 3 (Linoleic acid) and Omega 6 (Linolenic acid).

These two play vital roles in the following:

Growth and development
Brain functioning
Skin health
Hair growth
Metabolism
Reproductive system health
Cell membrane integrity.

The fact that are bodies can't make them makes them very important in our diet. They are most important in our cell membranes.

Omega 3 is an amazing anti-flammatory. It does this by blocking the inflammation pathways in the cell.

We need more Omega 3 than 6 - about a ratio of 2:1.

This is a pretty good page if you want more information.


How is temperature sensed? Can anyone summarize the mechanism by which when an object of a given temperature is placed in contact with, say, the skin on a human fingertip, the average speed of the particles of the object is converted into nerve signals to the brain?

If you can answer that, how about the format of how the temperature is encoded in the nerve signals?

In the periphery (e.g. on our fingertips), our body senses external temperature through nerve terminals, expressing certain TRP channels. These are ion channels that are sensitive to temperature (note that TRP channels can be sensitive to several things, such as pH, light, and stretch) and allow entrance of cations in the cell when the temperature is higher or lower than a certain threshold.

Six TRP channels have been described as been involved in sensing different temperature ranges1,2:

TRPV1 is activated at >43 °C
TRPV2 at >52 °C
TRPV3 at ~> 34-38 °C
TRPV4 at ~> 27-35 °C
TRPM8 at ~< 25-28 °C
TRPA1 at ~< 17 °C

Not surprisingly, TRPV1 and TRPV2 are also involved in nociception (=pain perception).

The exact molecular mechanisms by which different temperatures open different TRP channels are unclear, although some biophysical models have been proposed.3

I am not sure of the exact "format" in which sensory fibers encode different temperature, but I would assume that the neuron would fire faster the more the temperature is distant from the specific threshold (hot or cold).

1 Thermosensation and pain. - J Neurobiol. 2004 Oct;61(1):3-12.
2 Sensing hot and cold with TRP channels. - Int J Hyperthermia. 2011;27(4):388-98.
3 - Thermal gating of TRP ion channels: food for thought? - Sci STKE. 2006 Mar 14;2006(326):pe12.


Why don't fish groom each other? Fish are often plagued by external parasites, which are presumably difficult for them to remove.

There are well known cases where large fish come to coral reefs and allow smaller fish to pick off their parasites. See below a moray eel being "cleaned" by a shrimp.

Some fish, like sunfish, even get cleaned up by birds: https://www.youtube.com/watch?v=U60obmWODLQ

But on land, we have many social animals that solve this problem more directly by grooming each other. How come the fish never seem to do this? Many of them are already social, and I imagine they wouldn't have much trouble digesting the external parasites. Why don't they groom each other?

All cases of same species grooming I know of involve animals with a certain amount of dexterity. For example (images from wikipedia):

Macaw beaks:

Primate fingers:

Even ponies rubbing each other:

In all of these cases, the animals involved have the right tools for the job. fingers, beaks and prehensile lips can all close in on a parasite and remove it with precision. how exactly would you expect a shark to do this (image from the guardian)?

Sharks can and do rub themselves against rocks to get rid of dead skin but they simply don't have the tools for the kind of detail work that the smaller fish can do for them. The same applies to other fish. I think you will find that at least in most cases, fish that use client species to groom themselves wouldn't be physically able to do the same job themselves. It's all a matter of the right size and the right tools.

Note that this is pure speculation, I have no references to back this up, it just seems reasonable. I would not be surprised if some fish did actually indulge in social grooming, it's just harder for the reasons outlined above.


Is Plasmablast a precursor of Plasma cell? I read it in Roitt's Essential Immunology.

  Plasmablasts are precursor cells of short- and long-lived plasma cells and
  are generally described as a proliferating fraction of
  antibody-secreting cells, often found in the bloodstream
  emigrating to organs such as the bone marrow.

I coudn't find any authentic source repeating the same.

Is it true? Is this book authentic enough to follow?

Antigen activated B-cells enter the germinal centre dark zone to form centroblasts which undergo somatic hypermutation. These then form centrocytes in the light zone. The various possibilities/routes the centrocyte can take are shown in the following figure. If the centrocyte undergoes a class switch recombination, it becomes a plasmablast.

A plasmablast is  defined as

  Plasmablast

  The B-cell lineage precursor of non-dividing plasma cells, which has the capacity to divide and that has migratory potential.

Once it matures as a plasma cell, it is out in the blood secreting soluble immunoglobulins or antibodies.

Another important definition to mentioned here would be of antibody secreting cells.

  Antibody-secreting cells

  A term that denotes both proliferating plasmablasts and non-proliferating plasma cells. The term is used when both cell types might be present

So, yes, they indeed are a precursor of plasma cells.

Also, it is necessary to clarify here that although both plasma cells and plasmablasts are antibody secreting cells, plasma cells lack membrane bound antibodies while plasmablasts retain them.

Finally, this is just the germinal centre response that is shown over here. Plasma cells and plasmablasts can also form in an extrafollicular response in extrafollicular sites in the spleen or in the medullary cords of the liver. That's another story altogether!

For a more detailed explanation, have a look at my other answer.

Image and reference: http://www.nature.com/nri/journal/v8/n1/full/nri2217.html


Introductory literature for synthetic / systems biology I am a computer engineer (MSc in Computer Engineering) who's looking to switch into the field of synthetic / systems biology. I have a comprehensive layman's understanding of evolution, genetics, transcription, etc, but my academic studies have been in the areas informatics, computer science, computer engineering and mathematics.

Does anyone have a good recommendation for standard literature in the field, to get me up to speed?

Systems Biology

Wingreen & Botstein who run the graduate systems biology course at Princeton wrote a paper about how to teach the subject (Wingreen & Botstein, 2006). In the paper they highlight the key concepts they think are crucial to understanding modern systems biology, and they teach the course through discussion of seminal papers in the field.

Here's the reference...
Wingreen, N. & Botstein, D. (2006) Back to the future: education for systems-level biologists. Nature Reviews Molecular Cell Biology. 7 (11), 829–832.

The paper is unfortunately not open access, so for those who can't access the paper  edit: @uvesten found a free PDF copy! I have listed their choices below, along with the key concept they think each provides...

Robustness (i.e. retaining function despite fluctuations)
Barkai, N. & Leibler, S. (1997) Robustness in simple biochemical networks. Nature. 387913–917.

Evolutionary perspective
Eisen, J.A. (1998) A phylogenomic study of the MutS family of proteins. Nucleic Acids Res. 264291–4300.

Microarray analysis (and more generally, the importance of data visualisation)
Eisen, M.B., Spellman, P.T., Brown, P.O. & Botstein, D. (1998) Cluster analysis and display of genome-wide expression patterns. Proc. Natl Acad. Sci. USA. 9514863–14868.

Individuality of elements in a system:
Elowitz, M.B., Levine, A.J., Siggia, E.D. & Swain, P.S. (2002) Stochastic gene expression in a single cell. Science. 2971183–1186.

Maximum likelihood
Felsenstein, J. (1981) Evolutionary trees from DNA sequences: a maximum likelihood approach. J. Mol. Evol. 17368–376.

Ultrasensitvity
Goldbeter, A. & Koshland, D.E. (1981) An amplified sensitivity arising from covalent modification in biological systems. Proc. Natl Acad. Sci. USA. 786840–6844.

Biophysical modelling
Hodgkin, A.L. (1958) Croonian Lecture, ionic movements and electrical activity in giant nerve fibres. Proc. R. Soc. Lond. B. Biol. Sci. 1481–37.

Specificity
Hopfield, J.J. (1974) Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc. Natl Acad. Sci. USA. 714135–4139.

Random processes and distributions:
Luria, S.E. & Delbruck, M. (1943) Mutations of bacteria from virus sensitivity to virus resistance. Genetics. 28491–511.

Stable switching between states:
Novick, A. & Wiener, M. (1957) Enzyme Induction as an all-or-none phenomenon. Proc. Natl Acad. Sci. USA. 43553–566.

Sequence similarity
Smith, T.F. & Waterman, M.S. (1981) Identification of common molecular subsequences. J. Mol. Biol. 147195–197.

Synthetic Biology

A good place to start in this subject is the Synthetic Biology network:

Syntheticbiology.org
iGEM.org
BioBricks.org


Can a human acquire a memory of an animal? I would like to know if it's possible for a human to acquire an animal memory.

I mean, animals store their memories in their brain, right? And so do we, humans, store our memory.

So, is it possible to cut off an inch (or something like that) of an animal brain,
also to cut off an inch of a human brain, and to replace that animal brain-piece in the missing part of the human's brain?

No, it can't be done for a lot of reasons. Here are just a few.

1) Memories are stored in electrical pathways, not the the cells themselves. You don't have 1000 memories in a chunk of brain that contains 1000 neurons. If you don't get the entire pathway, you won't get the memory.

2) Once a nerve is cut, it won't fuse with another cut nerve. All you'll have is a chunk of dying animal brain in your head. Even if a skilled neurosurgeon united the blood vessels of your brain to those of the chunk to keep it alive, the nerves themselves wouldn't become a working part of your brain. All you'd have (at best) is a useless chunk of another animal's brain sitting where your now-missing chunk was.

3) Animals are different from us. Your body would recognize the different-animal brain matter as foreign, and would make antibodies to it and reduce it to mush (if one didn't die of infection before then).


How to evolutionary explain menstrural cycles synchronization? Sorry, I can not indicate the source, but I read that menstrual cycles of women who live in the same house over time sync. Is it true? How does it work?

This is a myth which most likely came from methological flaws in the original study. It could never be reproduced. This paper ("Darwin’s Legacy: An Evolutionary View of Women’s Reproductive and Sexual Functioning") deals with it. The interesting part starts from page 30 and says (the references can be ressolved in the article):

  Critiques of MSH Studies

  Wilson (1992) and Yang and Schank (2006),
  among others, have criticized the study design, methods, and
  statistics used by McClintock (1971) and others who have claimed
  evidence of MS. For example, McClintock
  incorrectly used the Page test for ordered hypotheses with multiple
  treatments (she used the same groups of women repeatedly instead of
  independent treatments), making it impossible to evaluate the true
  level of significance of her reported findings. Likewise, reports of
  greater estrous synchrony in chimpanzees caged together than in those
  caged apart (Wallis, 1985) and synchronization of estrogen peaks in a
  sample of five golden lion tamarins (French & Stribley, 1987) are
  rendered moot by the use of unsuitable statistical tests (Schank,
  2001). Furthermore, computer simulations suggested that the null
  hypothesis of no synchronization could not be rejected in either the
  chimpanzee or tamarin samples (Schank, 2001).


Why do protein solutions have to be alkalised in biuret test? I’ve read that CuSO4 solution reacts with peptide bonds that connect amino acids to create a violet colour, but the instructions always tell me to add NaOH solution to the protein solution before I add CuSO4. How is alkalising the protein solution before adding CuSO4 solution an aid to this process?

This is probably to prevent precipitation of copper hydroxide (see Itzhaki & Gill, 1964 - they suggest adding dilute copper sulfate slowly to the NaOH solution to avoid this). If you have the protein already alkalized and ready to react you'll get the color reaction before precipitate forms.

Commercial premixed solutions, like @canadianer mentioned in a comment, have tartrate present to prevent this (Geiger & Bessman, 1972 mention this).

It doesn't seem like it's strictly necessary to add NaOH first, but that's probably the most reliable way to do the assay without using an additional stabilizing agent.

Itzhaki, R. F., & Gill, D. M. (1964). A micro-biuret method for estimating proteins. Analytical biochemistry, 9(4), 401-410.

Geiger, P. J., & Bessman, S. P. (1972). Protein determination by Lowry's method in the presence of sulfhydryl reagents. Analytical biochemistry, 49(2), 467-473.


Looking for books on How the limbic system works and it role in non-verbal behavior This is my first post. I just read and I'm currently studying a book called "How everybody works" as a guide to understanding nonverbal behaviors.

After I'm done studying it and while I experiment with its claims; I'm looking to understand more of how the limbic system works and its role in human emotions.

The book's premise is that the limbic system makes us react to certain situations in such ways that nonverbal behavior is expressed; therefore by understanding the limbic system and nonverbal behavior we can ascertain a person's reaction to outside stimuli and gain insight.

If anyone could provide recommendations on books about the Limbic system
that are up to date with current finds or any other books that relate to the topics above I would greatly appreciate it.

not sure if you are still looking, but I have two recommendations for you.

"Limbic systems for emotion and for memory, but no single limbic system" is a really long, but really great article on the topic.  You can find that online here:  https://www.sciencedirect.com/science/article/pii/S0010945213003110?via%3Dihub
It's been a while since I've read this one, but the book Synaptic Self:  How Our Brains Become Who We Are is a good read on this subject.  It's about the brain as a whole, but focuses a lot on the limbic system and amygdala (it's author, Joseph LeDoux, did much of the pioneering work on the amygdala).  It is from 1996, so the science isn't super up to date, but I still think it's a good read if you're just curious about the brain and limbic system.


introduction to Chip Seq I hope this question is suitable for this site. I am concerned about the Chip experiment part so I think it should be okay. I am a Applied Math student starting to get into bioinformatics and so I've been looking at Chip Seq data. But to make sense of the Chip Seq data I wish to understand how the experiment is first performed.

Basically my question relates to step 1 of the following diagram:

Now my main question is how come the reads are overlapped? Where did we get so many of the (almost the) same reads?

My "understanding" is that:

1) They take a DNA sequence and crosslink the protien of interest. Then they get rid of the DNA sequence surrounding this area of interest so now we have a "small" sequence of DNA and in this small DNA is somewhere where our TF binds. Now we make copies of this small DNA seq and run it through a sequencing machine. Is this correct?

2) They take a bunch of cells = bunch of DNA sequences. Then they do the same procedure above (by crosslinking and getting a "smaller" DNA sequence of interest). Since they had many cells to begin with, this means they had many DNA seq to begin with. Now they shear the DNA seq and we have fragments. Then we align these up with the reference genome.

The basic steps of ChIP-Seq are:

Crosslinking proteins to DNA - this fixes the proteins in their natural positions
Nuclease digestion - this removes regions that are unbound to protein; nucleases are sterically hindered from digesting protein-bound DNA
Immunoprecipitation - this allows isolation of the target protein by binding it to a selective antibody
Sequencing to determine the bound DNA sequence
Mapping the reads to the reference genome

Why so many reads? They are taking many reads from different cells. Why are the reads so short? Many modern next-gen sequencing methods are limited to ~30 bp reads. Thus, the reads you see are not actually the entire protected sequence but rather just a shorter fragment from the 5' end (where sequencing starts from). The why behind this is explained by Jiang and Pugh, 2009 (Nucleosome positioning and gene regulation: advances through genomics):

  Three DNA sequencing technologies have been used to map nucleosomes. Pyrosequencing using the Roche 454 GS20/FLX
  sequences nucleosomel DNA end-to-end, allowing both nucleosome
  borders to be linked in a single sequence. This method provides the
  greatest mapping accuracy, particularly in genomic regions of low
  complexity. By contrast, other platforms, such as those provided by
  the Illumina-Solexa Genome Analyzer and Applied Biosystems SOLiD,
  generate only 25-35 by sequence tags, requiring both nucleosome
  borders to be inferred. Nonetheless, these short-read technologies
  produce >100 times the number of sequence tags at a similar cost as
  the long-read technologies, and so the short-read technology is
  currently the only practical technology for mapping nucleosomes in
  large genomes. The higher tag count of the short-read technology
  enhances mapping accuracy and thus provides a practical way of
  mapping nucleosomes.

Why are the reads overlapped? I can think of a few explanation for that. For starters, Protein-DNA binding is variable in its specificity. In other words, a given protein might bind at the exact same site every time or it may bind 'around' a site or it may bind randomly. A protein that binds an exact sequence would be expected to produce reads that are more in phase that one that binds more variably. Next, the nuclease digestion process is random (or at least expected to be). Thus the DNA cleavage point relative to the protein is variable and your reads start from different points. Again, from Jiang and Pugh:

  At any given genomic locus, the preferential positioning of nucleosomes--called phasing--can be described. At most loci, there is an approximately Gaussian (normal) distribution of nucleosome positions around particular genomic coordinates, ranging from ~30 by for highly phased nucleosomes to a random continuous distribution throughout an array. How much of this variation is due to genuine positional heterogeneity and how much is an artefact that is caused by overtrimming or undertrimming of the DNA at nucleosome borders by micrococcal nuclease during sample preparation remains to be determined.

Does that answer your question? Basically the reads are overlapped because there are many of them and they may differ either because of actual variance in the DNA binding site (which is biologically significant) or because of variance in the DNA digestion site (which is a methodological flaw). As with any biological experiment, you must perform many replicates to statistically determine the source of the variance and this is done by taking many reads. I recommend you read the article I quoted from, it is a good overview of histone mapping with ChIP and is likely also applicable to what you're studying.

Also, do you know why there are two sets of reads (red and blue)? I would venture a guess that they are taken from opposite strands. In other words, they are reads of the same DNA region taken from different directions. That might help clarify what's going on.

To conclude:

DNA is not extracted from a single cell. In usual procedures it is
always from a collection of cells or from tissues.
The overlap in TF associated reads arises because of the TF bound
sequence coming from different cells in this collection.
Each DNA piece is amplified and clusters are formed in the NGS
sequencers (for the ease of detection);
In a homogeneous cell collection i.e. all cells are of same type, the
variability in the read position usually arises because of
flexibility of binding sites (i.e TF wont exactly bind to at a
certain locus). Also, as previously mentioned the variability can
arise during the technical procedures.
In case of heterogeneous tissues the variability arises because of
different biochemical status of different cells. Strictly speaking
there is always some heterogeneity even in an apparently homogeneous
tissue but tissues such as brain are highly heterogeneous
In the case of nucleosomes the positioning is not exact because the
sequence contribution to the position is very minimal. Certain
nucleosome positions are tightly maintained for e.g. around the TSS
(transcription start sites) whereas in other regions the positioning
is fuzzy because of the dynamic nature of the chromatin.


What is this abbreviation CT in female reproductive system I have this sentence in my notes

  Ovary is surrounded by tunica albuginea and the cortex keeps the primordial follicles. The medulla containing CT and blood vessels develop from mesonephros.

I have these words in my mind about CT

tunica
cyto- (maybe cytotrophoblast)
corona (no other than corona radiata so not)

What can CT be here?

I think CT is an abbreviation for connective tissue. Some examples of its use in that fashion:

http://en.wikipedia.org/wiki/Connective_tissue

https://web.archive.org/web/20151024041339/http://www.vetmed.vt.edu/education/curriculum/vm8054/Labs/Lab5/Lab5.htm

http://www.pitt.edu/~sshostak/biosci1450/hislec03.html


Can DNA & RNA be considered as nature's programming language? The final frontier of Biological Sciences could be considered understanding the effects of variation in the DNA (and RNA).

If after fertilization the DNA of the zygote could be genetically engineered to prevent complications occurring later in the life of that human being, it could become the ultimate medicine.

Also, we know that (in humans) only 2% of the genome encodes genes that are translated into proteins; is the rest required for function?

Can DNA & RNA be considered the ultimate blueprint of all living organisms?

This question can't be answered with a simple yes/no, but I would say that the analogy of DNA being the "code" used by cells is a reasonable one, if taken with a number of other considerations.

DNA function

When Watson and Crick first described the structure of DNA (being a double-stranded sequence  of the nucleotides Adenine, Cytosine, Guanine and Thymine) this led to what is known as the Central Dogma of Molecular Biology [1], which posits that DNA makes RNA makes Protein (figure from [2], as originally produced by Watson).

As you correctly point out, less than 2% of the genome is protein-coding, however our understanding of the rest of the genome is increasing manifold due to projects like ENCODE [3], which are discovering not only the "regulatory" regions that control the expression of protein-coding genes, but also the discovery of non-coding RNA's, many of which are totally uncharacterised [4].

The point of this section is to clarify that although only 2% of the genome codes for protein, it is incorrect to say the rest is "junk" or non-functional. The Central Dogma described above is now an outdated model - certainly some DNA makes RNA makes Protein, but not all; many RNA molecules are functional in their own right.

You could argue that proteins and non-coding RNA molecules are the product of "scripts" in the DNA that are run or performed by cells, although you are unlikely to find any genomic scientists talking in these terms.

Epigenetic control

Where the analogy breaks down is that all* the cells in an organism have the same genome, yet they are vastly different to one another. These differences are due to epigenetic processes, which are described as non-coding modifications to the DNA that affect expression of transcripts. A basic overview can be found here [5].

These modifications come in several forms and include:

DNA methylation

the addition of a methyl-group to cytosine nucleotides that can affect binding of transcription factors etc,

Histone modifications

DNA is actually a 3-dimensional structure, and is wrapped around proteins called histones, which wrap together to form chromatin and the characteristic chromosomal structure.

The availability of DNA to transcription factors is completely dependent on these modifications to the DNA, which are specific to individual cell types and prevent retinal cells, for instance, expressing liver enzymes. (Below figure from [6])

Overview

In short, genetics and the DNA sequence can certainly be thought of as the blueprint for an organism - changes to this sequence can profoundly affect phenotype - however it is too simplistic to imagine that the sequence alone provides all the information needed.

Not only are there many non-coding molecules essential for functioning in cells, there is exquisite control over expression by DNA modifications that do not affect the sequence of nucleotides and are essential for cellular differentiation.

The ENCODE (Encyclopedia of DNA elements) project [7] is making headway into the interpretation of the non-protein-coding elements of the DNA, but there is still a long way to go.

* not quite all, for instance B-cells have a hypervariable region to enrich antibodies for variation [8]

http://www.ncbi.nlm.nih.gov/Class/MLACourse/Modules/MolBioReview/central_dogma.html
http://sandwalk.blogspot.co.uk/2007/01/central-dogma-of-molecular-biology.html
ENCODE Project Consortium, “The ENCODE (ENCyclopedia Of DNA Elements) Project.,” Science, vol. 306, pp. 636–640, 2004. PMID: 15499007
http://www.nature.com/encode/threads/non-coding-rna-characterization
http://www.whatisepigenetics.com/fundamentals/
http://www.eusem.com/main/CH/epi
http://www.genome.gov/encode/
http://www.anaptysbio.com/technology/somatic-hypermutation/


How to selectively download 3 fields from every record in UniProtKB? I want to download a comprehensive table of protein names from uniprot.org.

More precisely, I want to generate a tab-delimited table consisting of the id (accession), entry name, and protein names "columns" from the UniProtKB database.

I want to get these three columns/fields for all 80M records in UniProtKB, and I don't want to specify all those Uniprot IDs through, e.g., a bazillion URL-encoded queries.  Also, I need to do this from a host that I can access only through a text interface, which basically rules out browser-based solutions.

I just spent a couple of hours going back-and-forth over the Uniprot site's docs, and I can find nothing useful.  The Perl example given there1 shows how to download full records, but downloading every full record from UniProtKB would be too slow and onerous to be considered2.

Does anyone know how to modify the Perl example (or any other way) to download only the three desired columns from UniProtKB?

1 You need to click on the phrase "Perl example" to see the code.
2 I downloaded a small test sample of 1000 full records, I found that the size of the information I actually want from those records is only 0.2% of the total.  IOW, downloading the full records would take up ~500x as long as downloading only the desired information.

Use BioMart. It retrieves UniProt information and you can select the features that you want. These files wont be that huge. So  you can download it in your PC and SFTP to wherever you are doing your analysis. A better way is to install BioMart in your workstation. See the BioMart documentation.


How is fructose absorbed into the body I’m finding contradicting methods of   Fructose  transfer to blood

page no 264(10)One of which saYs fructose is absorbed by simple diffusion

And another sources like this say that fructose is absorbed by facilitated diffusion

I Believe that second source is true but still which one is correct ?

Fructose is absorbed by facilitated diffusion in the small intestine by the help of transport molecules GLUT5 or GLUT2.

Sources:

https://en.wikipedia.org/wiki/Fructose
http://diabetes.diabetesjournals.org/content/54/10/3056.long

The source you've mentioned (http://ncert.nic.in/ncerts/l/kebo116.pdf), says that certain monosaccharides, such as glucose, can be absorbed by simple diffusion, but it says nothing specifically about fructose.

In fructose malabsorption, in which the transporter GLUT5 is deficient, fructose absorption can be very decreased, which suggests there is probably no additional absorption of fructose by simple diffusion (PubMed).


Why are there no fresh water osmoconformers? I'm just having trouble understanding this. I know that often marine fish are osmoconformers, and freshwater (like bony fish) are often osmoregulators, but why?

There are virtually no freshwater osmoconformers but there are some exceptions like being both an osmoconformer and an osmoregulator based on the salinity of the environment.

Osmoconformers keep their internal fluids isotonic to their environment and they maintain an internal salinity similar to the surrounding water. The concentration of solutes in freshwater is very low and if any organism were to have that low concentration of solutes in its body, it would not have enough proteins, ions, etc. to effectively conduct the biochemistry of living.

Here is a rare example of a freshwater species Daphnia which can be both an osmoconformer and an osmoregulator:

  For freshwater osmoconformer species, most of the time there is a gradient between their internal
  osmotic concentration and that of the external environment; consequently, osmoconformers will
  vary in their cellular osmotic volume contents and as a result, some FW species (e.g. Daphnia),
  osmoregulate at low salinity levels but are osmoconformers at raised salinities. Some physiological
  processes, including reproduction and metabolic rate however, can be affected negatively by these
  changes (this group regulate their osmotic pressure actively) (Chen and Stillman, 2012).

  https://eprints.qut.edu.au/107457/1/Azam_Moshtaghi_Thesis.pdf

Additionally, there is the term euryhaline used for the aquatic organisms who are able to tolerate a wide range of salinity. There are fish species that can live in salt water, fresh water and brackish water. You can see a list in the Wikipedia/Euryhaline Article.


How can two individuals of the same species have different chromosome numbers? It is known that male drones develop by arrhenotoky, and have haploid chromosome constitution, whereas the queen bee and workers are diploid.

Thus we can see two different types of ploidy occurring in the same species. Sill the drones and queen bee are successful in mating and producing offsprings. This would require the queen to produce haploid gametes by meiosis and haploid gametes from haploid drones.

Doesn't this create a problem in defining species?

there are diverent concepts of definitions of species:

morphological species concept, distiguishes a species by body shape and other structural features
ecological species concept, distighuishes a species according to it's niche
phylogenetic species concept, smallest group which schare a common ancestor
biological species concept, a species is a group whose members can produce fertile offspring

the biological species concept is most commonly used, if we apply this on your problem, they still produce fertile offspring, so they are the same species.

If for example a mutation wil occur which causes polyploidy (more likely in plants, however it's possible in some animals). Let say the orginal species have 2n = 12, if polyploidy occurs(during meiotic error for example). We will have 2n = 24. If these species produce gametes n = 6 and n =12, fusion of those gametes will result in unpaired chromsomes, which in turn will lead to a reproductive barrière. The 2n =12 and the 2n = 24 species can only mate with each other to produce fertile offspring, so we can say these are different species.


What are these bladder snail parasites? I collected some bladder snails several months ago. While checking them out one day, I noticed that they were now infested with worm-like ectoparasites.
Appearance and behavior
Here's a picture of a snail with a bunch of the worms hanging off of it's head, where they tend to congregate. I've also circled one of the worms crawling along the glass.

I sampled some of the worms and took a look at them under a microscope. Here's a video ("Video 1" below) I recorded of one of them crawling around. They have some notable characteristics.
First, they appear to have some sort of sucker mouth.

Second, they have some interesting "legs" tipped with hairs (?) at the ends of their tails. Here's a short video ("Video 2" below) of a worm writhing around that shows them off a little better than pictures do. They appear to be in pairs of two.

Animated clips from the linked videos:

 Video 1 (left) and Video 2 (right)
The length of the worms ranges from 1-5 mm (edit: they get larger; see below).
Update: After keeping infected snails for a while longer, I believe that these worms only parasitize bladder snails when the worms are young (within the aforementioned size range). Larger, adult worms appear to be free-living and growing up to 1-1.5cm, and will actually crawl away when snails disturb them. Here is a picture of an adult specimen (along with some smaller ones), no microscope required:

Here's a much better picture of the hair-like legs, of which this adult specimen has numerous pairs:

Lastly, here's a very interesting detail: These worms are highly specialized, and do not seem to affect ramshorn or pond snails, which I have numerous of in the same tank, in the slightest. It's only the bladder snails that end up infested.
Location
These snails were gathered in Canada, in a still-water area connected to the Oldman River. The river is accessible by cows and deer.
Reproduction
I have witnessed the snails shedding tons of cercariae into the water, which eventually disappear after a couple of hours (reinfect the snails?). I'm not sure if those are related to this worm, or if the snails are also infected with some other type of fluke.
Update: I now believe the aforementioned cercariae are unrelated to the worm in question. I managed to record an adult worm releasing numerous live young, which resemble tadpoles (trochophores?):

I've recorded a video of the worm giving birth that can be viewed here (left image below). The young seem to be stored in chambers inside of the parent, and then are pumped through the body and out the back end. While the young appear to be still in the video, some of them are quite active (right image below).

My theory at this point is that the young penetrate snails, grow inside of them, emerge and hang onto the host for a while, and then eventually dismount as free-living adults. Adult worms seem to be independent, while smaller worms hang off of the host the snail (feeding off of it?) until they're large enough to live freely.
Treatment
I would like to eliminate these worms if possible (I can't gather more snails any time soon, and they eventually kill off smaller snails). My first attempt was dosing with praziquantel, which is supposedly effective against flukes while being snail-friendly. Unfortunately, three days later, one of the snails died, and the worms appear to be unharmed.
Update: I gathered some more snails, and attempted praziquantel once again. While it did not harm the snails, it also continued to be ineffective against the worms. I have been experimenting with Seachem ParaGuard, and the results seem to be positive for minor infestations, but not against fully mature worms.
Conclusion
After some research, my best guess is that they're trematodes from the class Digenea-- They appear have sucker mouths, can parasitize snails exclusively, can have a free-swimming form, and can shed cercariae. That said, I'm not terribly confident, and would ideally like to be able to identify them more specifically.

I have finally figured out what these are, and it turns out I greatly misunderstood their relationship with snails.
These worms are annelids of the genus Chaetogaster, specifically Chaetogaster limnaei limnaei.

Source: Page 653 of "Fresh-water biology" (1918)
Ch. l. limnaei is unique in its genus in that lives on the bodies and in the shells of snails, including Physa spp. like the Physa acuta snails in question. While the relationship was originally thought to be parasitic by early researchers, it turns out that it's actually commensalistic (or even mutualistic in some scenarios).
From this vantage point the worms feed on various microorganisms, such as rotifers and algae, and small particles stirred up by the host snail scavenging for food. They also feed upon the cercariae and metacercariae of fluke species that parasitize the snails, even able to protect the snails from getting infected in the first place.
That said, it's not all good-- Snails with heavy infestations of Ch. l. limnaei have been shown to be less active, spending more time in their shells rather than out and foraging for food (Stoll et al., 2013). Additionally, worms have been experimentally shown to consume tissues of their hosts when food is low or nonexistent (Stoll et al., 2013).
To respond to a few points from the question:

These worms are highly specialized, and do not seem to affect ramshorn or pond snails, which I have numerous of in the same tank, in the slightest. It's only the bladder snails that end up infested.

Ch. l. limnaei is not restricted to bladder snails, and will happily live on pond snail and ramshorn species. It's possible that the bladder snails had more severe fluke infestations which the worms found preferable.

My theory at this point is that the young penetrate snails, grow inside of them, emerge and hang onto the host for a while, and then eventually dismount as free-living adults. Adult worms seem to be independent, while smaller worms hang off of the host the snail (feeding off of it?) until they're large enough to live freely.

This worm is able to reproduce both asexually through budding, but also sexually as shown here. Sexual reproduction often occurs in the winter, where the worm lives freely and reproduces sexually before returning to snail hosts in the spring.

I would like to eliminate these worms if possible

I found a blog post by someone struggling with the same problem:

One day (do not know it exactly, probably few months later) I noticed that all worms disappeared. I did not know why they were gone.
Later I found the reason in the 1974 thesis. Chaetogaster limnaei limnaei is highly sensitive to temperatures above 24 °C. Such a temperature reduces or completely eliminates these worms. Therefore, If you transport worms from their natural environment to your tropical aquarium, there is no need to worry. If you have aquaria with aquarium heater, they are bound to be killed by high temperature. Worms are killed in summer heat as well.

This seems to be accurate, as with the onset of the summer heat, I no longer have any of these worms present on my snails. Now knowing what they were, it almost feels like a shame-- They were protectors, not foes.
References

Density-dependent relationship between Chaetogaster limnaei limnaei (Oligochaeta) and the freshwater snail Physa acuta (Pulmonata)


Why does affinity of Hemoglobin increases for Oxygen in carbon monoxide poisoning? I have studied this in almost every physiology book but I just can't understand how carbon monoxide can affect oxygen's affinity to Hemoglobin. I know that there is left shift in oxygen dissociation curve but  why?

Affinity for any ligand to a protein is a function of the shape of the protein which provides some place for the ligand to bind/interact.

Hemoglobin typically exists in tetrameric form: it is a collection of 4 subunits that each bind 1 molecule of oxygen.

The shape of hemoglobin is affected by CO2/pH, which is important for having high affinity for oxygen in the lungs and lower affinity for oxygen in tissues where a lot of CO2 is released (i.e., where there is a high rate of metabolism).

The shape is also affected by binding oxygen itself: binding oxygen to one subunit causes conformational change in the other subunits of the tetramer, increasing their affinity for oxygen. This is called "cooperative binding."

So, how does any of this relate to CO? Well, it turns out that not only does CO bind very tightly to hemoglobin in the place oxygen would normally bind, taking up space and reducing the capacity for oxygen, it also very strongly increases the affinity of the other subunits for oxygen. It increases the affinity enough that even in the low-oxygen high-CO2 environment of the capillaries, carboxyhemoglobin (hemoglobin bound to CO) continues to hang on to rather than release oxygen. This is represented by a shift in the dissociation curve to the left: oxygen stays bound even when the concentration is low.

This means that fewer CO molecules are necessary to cause deficits in oxygen transport than would be needed if it was only taking up space: one CO molecule binding to a hemoglobin tetramer effectively prevents transport of up to 4 molecules of oxygen.

As a quick caveat, I believe some of the biophysics here are still incompletely understood, so please consider this answer to be an approximation and an explanation of experimental findings to a level of precision sufficient to understand the pathophysiology of CO poisoning. More depth is necessary for a biophysical approach.

Roughton, F. J. W., & Darling, R. C. (1944). The effect of carbon monoxide on the oxyhemoglobin dissociation curve. American Journal of Physiology-Legacy Content, 141(1), 17-31.

Eaton, W. A., Henry, E. R., Hofrichter, J., & Mozzarelli, A. (1999). Is cooperative oxygen binding by hemoglobin really understood?. Nature Structural & Molecular Biology, 6(4), 351.


What is this plant/creature in my freshwater aquarium? I've been noticing these really small creatures (or plants, I'm unsure) in my tank recently. They measure less than 1cm in length and I've only seen them at the bottom of my tank; some attached to the gravel and some to the glass. They have tentacle-like appendages on the end of their stem(?) and seem to drift with the with the water movement rather than on their own accord.

My tank is a planted tropical freshwater.

What is this plant/creature in my tank?

Any additional information on whether or not these are harmful to my fish would be appreciated.

That is a hydra.
They are a kind of jellyfish, and as such they do technically have stinging tentacles. However, they're also very small, so they're not a danger to most fish or shrimp. If you're planning on breeding your fish they will eat fish fry if they get a chance. On the other hand some fish species will eat them, so it's a bit of a wash.
Generally they only thrive in tanks with extra food hanging around, so you may consider feeding a little less than you have been.