Dopamine paradox in schizophrenia If there is more dopamine action in the mesocortical pathway in schizophrenia, then schizophrenics should always be in euphoric state. Instead, schizophrenics often lack motivation and do not experience pleasure. Why?

Short answer
The dopamine (DA) hypothesis suggests that excessive DA transmission in the mesolimbic pathway in schizophrenia leads to hallucinations and other positive symptoms. It explains the negative symptoms of schizophrenia (flattened affect, reduced motivation) by reduced DA activity in the mesocortical pathway affecting the frontal cortical regions.

Background
You are referring to the dopamine hypothesis of schizophrenia.

The initial dopamine (DA) hypothesis focused primarily on the positive symptoms of schizophrenia, namely the active psychoses, which includes periods of hallucinations and delusions. These effects can be attributed to hyperactivity in subcortical dopaminergic pathways. Specifically, excessive subcortical release of dopamine is thought to increase D2 receptor activation, disturbing the cortical pathway through the nucleus accumbens (Brisch et al., 2014), called the mesolimbic pathway (Fig. 1). These positive effects can be treated quite effectively with the classical, first-generation anti-dopaminergic antipsychotics such as haloperidol and chlorpromazine.

However, there is another important aspect on schizophrenia, which are the negative symptoms. While the full-blown psychoses occur in waves, these negative symptoms are a more continuous and persistent phenomenon. The symptoms include a flattened affect and dysphoria (reduced pleasure in life). These symptoms are thought to occur due to altered prefrontal cortex (PFC) functioning. Specifically, they are thought to be induced by hypoactivity in dopaminergic D1 transmission (Brisch et al., 2014) in the mesocortical pathway (Fig. 1).

Fig. 1. The dopamine pathways in the brain, including the mesolimbic and mesocortical pathway, implicated in the positive and negative symptoms of schizophrenia, respectively. source: Wikipedia.

These two sides of schizophrenia point to an imbalance in DA activity in the brain, namely hyperactive subcortical mesolimbic D2 activity leading to positive symptoms, and hypoactive mesocortical D1 activity in the PFC resulting in negative symptoms. This imbalance hypothesis is the revised DA hypothesis and it is still an accepted working model (Brisch et al., 2014).

However, as noted by others, schizophrenia is a complex disease and it is thought that besides DA, also serotonin, glutamate and GABA play a role (Olijslagers et al., 2006). The current first line of treatment of schizophrenia are atypical neuroleptics, such as Clozapine. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. The broad effects of Clozapine are thought to underlie its potent antipsychotic therapeutic effect. It is believed it mainly works through a combination of antagonistic effects at D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal cortex. D2 antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms.

References
- Brisch et al., Front Psychiatry (2014); 5: 47
- Olijslagers et al., Curr Neuropharmacol (2006); 4(1): 59–68


How are neural pathways discovered? I have seen the spinal cord and it's a white, soft, slippery cylinder that has a small diameter (about 25-30 milimeters). It absolutely doesn't have a macroscopocally reticular texture that would allow us to track down individual pathways. Same goes for the brain, it's also not macroscopically reticular and yet we know a lot of connections inside the brain.

So what's the technique used to discover these neural pathways and the information about in which parts of the pathway are synapses located?

Example of what we know is here under the "Major neural pathways" title.

There are are few ways this can be done.

One important example, is case of Phineas Cage who's accident lead to severe brain damage. This changed his behavior, which allowed scientist to connect physiology with behavior. Namely, left frontal lobe damage caused change in personality, without significant change in other important behaviors such as memory.

Same way we can look on naturally occurred brain damage via modern imaging techniques (X-ray, CT, MRI, fMRI) and connect those to behavioral abnormalities.

We can also learn about neural substrate of behavior by experimenting in the lab: by looking at effects of tissue damage. Basically, you ask "what happens if we damage this part of the brain". This way we can figure out parts of brain that regulate different parts of sleep by dissecting animal's brain stem in different regions.

Another option is to "look" at brain while it functions and detect important active regions. Here you can use any number of techniques: fMRI, EEG, direct electrode probing of brain regions, or in animals optical calcium imaging. Point is that in these experiments you ask (or make) your subjects to perform behavior X and see how and where that behavior activates neurons.


How do susceptible organisms prevent parasites from overcoming resistance? Bt corn is genetically modified to kill borers, but "regulations require farmers to plant conventional varieties as well, which is intended to stop the borers becoming resistant."
-Source

How do susceptible organisms prevent parasites from overcoming host resistance?

In an environment where all plants are resistant to certain parasites, a rare breed which has a mechanism against this resistance has free play - lots of food and no competition. However, in plants which do not have the resistance, this rare parasite breed may be at a disadvantage compared to parasites who do not have the mechanism against that resistance (even if only because they do not waste energy on a defensive mechanism they don't need).

By mixing resistant and unresistant plants, it is probably possible to maintain high enough a competition of parasites without that defensive mechanism to prevent the ones with the mechanism from developing. It's natural selection at work :)


If a human is stranded with beer but no water, should they drink it? TL;DR: At what percent (if any) will alcohol dehydrate you more/faster than drinking nothing?

Let's contrive a situation for dramatic effect...

A human goes out on a boat for a nice sail in the sea. But oh, the sea was angry that day, my friends. The weather turns, and the sailboat is tossed asunder. Luckily, our survivor grabs hold of some debris and is washed onto a deserted island.

Lo and behold, the debris that floated with the survivor to the island is a cooler, and it is filled with beer! There are no other food or water sources on the island. What should our survivor do in regards to the beer to stay alive for as long as possible?

The crux of the situation and my question: will drinking the beer help hydrate the human, keeping them alive longer? Or would the effect of the alcohol as a diuretic actually dehydrate them, causing an earlier demise?

Details and follow up questions:
Let's assume this is an average beer ~4% alcohol. However, I know there must be a breaking point. Some kombucha or ginger beer with .5% alcohol should surely be imbibed. But should this beer still be drunk? What if instead it was a 7% IPA? Or a 14% quadruple IPA like I have in my fridge? What about wine, whiskey, or gin?

How would the situation change for a caffeinated beverage like coffee? Or what if the cooler was filled with energy drinks?

I look forward to your answers!

EDIT: The linked question, while similar, does not answer my question. It links to one 1996 study that talks about the effect of alcohol on rehydration, but not the specifics of yes, probably ok to drink at about this percent ABV, and no don't drink at above this percent. It also doesn't discuss rate of intake, changes based on body weight, etc. which are all things I would surmise have an impact on this. I understand there isn't going to be a hard and fast STOP percent level, but I would like to understand more about the underlying mechanisms and factors that change things.

There is quite a lot of misunderstanding about alcohol (and caffeine) as a diuretic. It's not nearly as cut and dry as you're presenting.

There is no answer to your question. Sodium and water are very tightly regulated, and a lot has to go wrong before they fail. If alcohol could easily derail water regulation, there would be far, far fewer alcoholics in the world.

Alcohol is primarily a toxin, not primarily a diuretic. The diuretic effect of alcohol depends partly on your hydration status. If you're fully hydrated, you'll produce slightly more urine on drinking an alcoholic (>2%) beverage than when you drink water. If you're dehydrated, your body will conserve the water more. The more alcohol in the drink, the less value it has as a rehydrating solution.

You won't find good studies because it's not a scenario truly worth studying. The toxic effects of alcohol are already known and bad enough. It would be unkind to conduct a study where higher concentrations of alcohol were the sole fluid available and length of survival on animals, let alone humans.

N.B. There have been lots of studies with acute alcohol intoxication and diuresis because that is a scenario that occurs, and which can be mitigated.

Effects of a moderate intake of beer on markers of hydration after exercise in the heat: a crossover study
Hydration Status and the Diuretic Action of a Small Dose of Alcohol


Is nuclear DNA immuno-privileged? It is well known that if DNA occurs in the cytoplasm of eukaryotic cells, an immune response may be triggered through a myriad of DNA receptors and pathways as part of the immuno response. Yet, apparently the nuclear DNA does not induce any type of such response. Is it known why this happens? Is it just due to the fact that the nuclear DNA is immuno-privileged?

Pattern recognition receptors (PRRs) can potentially discriminate between endogenous and exogenous DNA:

  Microbial nucleic acids can be discriminated from self nucleic acids using various parameters, such as their sequence, their tertiary structure, their molecular modifications and their localization. In addition, mislocalized DNA and RNA can be an indicator of cellular damage and infection. [1]

and

  Microbial nucleic acids are discriminated from self nucleic acids based on different parameters, such as their sequence, structure, molecular modifications and localization. On the other hand, mislocalized self nucleic acids — such as extranuclear DNA or extracellular RNA — can be recognized as DAMPs, probably because they are reliable indicators of cellular damage. [2]

Somewhat suspect is the similarity of those quotes; I only link to both reviews so as to include both in the references for further reading.

Distinguishing by sequence and structure are self-explanatory. Molecular modifications could include unmethylated CpG sites which are more common in bacterial and viral genomes and are recognized by TLR9. [3] Mislocalized DNA means any that is found outside the nucleus, which is a sign of damage or infection. Most of the well-studied nucleic-acid-recognizing PRRs are found outside the nucleus: TLRs are constrained to endosomes and the extracellular environment while RLRs are found in the cytoplasm. The as of yet identified DNA sensors like DAI also seem to localize to the cytoplasm. Extranuclear PRRs do not necessarily need to discriminate between endogenous and exogenous DNA: any that they sense is mislocalized. However, at least one dsDNA-recognizing PRR, IFI16, localizes to the nucleus as well as the cytoplasm, where it can recognize viral dsDNA. [4]

  It has been assumed that cells distinguish viral from cellular DNA due to the former's presence in the cytosol. However, … Kerur et al. (2011) propose that the DNA genome of Kaposi's sarcoma-associated herpesvirus (KSHV) is recognized inside the nucleus by the DNA sensor IFI16, leading [to] inflammasome activation. [5]

IFI16 apparently distinguishes exogenous from endogenous DNA by its length. [6]

Endogenous DNA is present in vivo as chromatin and the amount of exposed linker DNA between histones is too short to promote the cooperative binding and oligomerization that IFI16 requires for signalling (B). An older model, where IFI16 binds independently, is also shown (A), but it suggests that IFI16 should bind self-DNA and doesn't fit with experimental results.

That is just one specific example of how a PRR can distinguish self from non-self. DNA sensors actually seem to be on the cutting edge of research into the innate immune system and, as such, the complete picture has yet to be determined.

References:

Broz P, Monack DM. 2013. Newly described pattern recognition receptors team up against intracellular pathogens. Nat Rev Immunol 13(8):551-565.
Desmet CJ, Ishii KJ. 2012. Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol 12(7):479-491.
Yoneyama M, Fujita T. 2010. Recognition of viral nucleic acids in innate immunity. Rev Med Virol 20(1):4-22.
Kerur N, Veettil MV, Sharma-Walia N, Bottero V, Sadagopan S, Otageri P, Chandran B. 2011. IFI16 Acts as a Nuclear Pathogen Sensor to Induce the Inflammasome in Response to Kaposi Sarcoma-Associated Herpesvirus Infection. Cell Host Microbe 9(5):363-375.
Unterholzner L, Bowie AG. 2011. Innate DNA Sensing Moves to the Nucleus (comment on Kerur et al., 2011). Cell Host Microbe 9(5):351-353.
Morrone SR, Wang T, Constantoulakis LM, Hooy RM, Delannoy MJ, Sohn J. 2014. Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy. PNAS 111(1):62-67.


Why HIV patients have greater virulence of M.tuberculosis? I am reading Murray Microbiology book.

Some facts

M. tuberculosis is an intracellular pathogen.
At the time of exposure, M. tuberculosis enters the respiratory airways and infectious particles penetrate to the alveoli where they are phagocytised by alveolar macrophages.
In contrast with most phagocytised bacteria, M. tuberculosis prevents fusion of the phagosome with lysosomes (by blocking the specific bridging molecule, early endosomal autoantigen 1 [EEA1]). NB probably here something relevant
At the same time, the phagosome is able to fuse with other intracellular vesicles, permitting access to nutrients and facilitating intravacuole replication.
Phagocytised bacteria are also able to evade macrophage killing mediated by reactive nitrogen intermediates formed between nitric oxide and superoxide anions by catalytically catabolising the oxidants that are formed.
Dissemination to any body site occurs most commonly in immunocompromised patients, like HIV patient.

If you read this article, you will find that CD4+ and CD8+ T-cells are probably the major mediators of the immune response against M. tuberculosis. Since HIV severely depletes the number of CD4+ T-cells (and to a lesser extent other kinds of lymphocytes), it stands to reason that the frequency of infection and virulence will be substantially increased in such patients.


When did human ancestors learn to walk? Where does our ancestor learn to walk from? How do we control our legs whenever we take a step?  I confuse every time whenever I take one step.

In a sense, there's an easy answer to your question.  Humans became bipedal in Africa, since bipedality is well-established for the first species in the human lineage to leave Africa (Homo erectus/Homo ergaster).  This can be verified in many textbooks.  However if you ask the question when, in what species, or why, there's no easy answer to your question. The question comes down to (a) which fossils are specifically ancestral to humans (b) what fossils have evidence for bipedality, and (c) theories as to why those species became bipedal.

The narrow sense of humans, Homo sapiens, has been bipedal ancestrally.  Other closely related species were almost certainly bipedal (Homo neanderthalensis and Homo heidelbergensis for example).  In fact, the species or species complex from which humans likely arose, Homo erectus, was also likely bipedal (discussion below).  If we take the broadest sense of what "human" means, it could mean any species which split from the human lineage after the split with the extant great apes (specifically, post split with chimpanzees).  Here there's reasonable evidence for bipedality exists around the same time as this split, but not in all species.  Specifically, Orrorin tugenensis is a 6 million year old specimen with some (but not conclusive) evidence for bipedalism.

Question b, how do we know a fossil creature is bipedal, is a challenging question.  Homo sapiens, the only completely bipedal primate, have many adaptations which facilitate walking on two legs.  The shape of our pelvis facilitates the muscle attachments necessary for walking by flaring the ilium (the bone which forms the upper part of the pelvis).  This same flaring is found in Australopithecus afarensis (which includes the famous "Lucy" specimen), about 3 million years ago.  Australopithecus also has a fossil of footprints, which seems to indicate bipedal movement.  The human femur is bent inwards and the neck is thickened to support the weight of someone walking upright.  This same thickening is found in Orroin tugenensis and the angle in Homo erectus/Homo ergaster (these are two names which are either closely related species or the same species, depending on who you ask). The human big toe is also in line with the others in the foot, which likely allows us better motion on the ground.  This feature is also true of Ardipithecus ramidus, at about 4.5 million years ago.

The third part of your question, why humans became bipedal, is largely speculative.  Many theories exist for the process which lead to bipedalism.  A popular theory in the 1970s and 1980s was that humans became bipedal to enhance our abilities to see across tall grass, because many people thought Homo erectus/Homo ergaster was the first upright walking species, and grasslands dominated east Africa at the time.  However since earlier evidence for bipedality, many people have abandoned this hypothesis in favor of others.  These other hypotheses include that bipedalism arose after scaffolding on to arboreal (tree-living) adaptations.  If human ancestors lived in trees, they may have moved in a vertical posture, leading to many of the adaptations needed to move vertically on the ground.  Others include an increased reliance on meat, caught through endurance hunting, or even wading into tidal waters being the key feature (notably this is not the aquatic ape hypothesis, which is pseudoscience), and this reliance on key marine resources provided the essential stable food supply for brain enlargement.  The short answer is that there's a tremendous amount of speculation in this area, and few firm facts.

Whichever of these species you choose as the "first bipedal human," and how confident you want to be about that bipedality, they all evolved in Africa.


blast search against UNIPROT I would like to ask how i can search in blast against UNIPROT (TREMBL PLUS SWISSPROT) for a selected organism. In the BLAST site there is no option about UNIPROT(only Swissprot), and in the uniprot site i cannot limit the results only in one organism(E.COLI).
THANKS A LOT!!!

You can blast for E.coli proteins only using Uniprot. Firstly, you restrict the search to the "target database" UniprotKB...Bacteria. After performing the blast search, you can further restrict your search results to include only hits for one "Popular organism", e.g. "Escherichia".


recombination frequency problem Three loci C, D and E are located on the same chromosome in this
  order. We found that the frequency of recombinants between C and D is
  10% and that between D and E it is 20%. Assuming that crossing over
  occurs randomly on the chromosome, what is the expected frequency of
  recombinants between C and E?

I know that it should be less than 30% (10%+20%) but the answer given is 26%. I don't understand how they figured that out.

Edit :

The frequency of recombination is <30% because of the chance that a crossover happens between C and D & also between D and E. The probability of that to happen is 2% (10/100 X 20/ 100)
So, why is it 26% instead of 28% ?

Another posssibility : Am I totally off the track ?

I got $26$% as the answer.

To get a recombination between C and E, there are two possible mechanisms:-

C and D produce a recombinant, but D and E remain linked, therefore the final genotype will be a recombinant considering C and E(Chiasmata between C and D). Here $P_1=P_{CD}\times P'_{DE}$ where $P$ is the probability of recombination and $P'=1-P$ is the probability of linkage.Hence $P_1=0.08$
C and D remain linked but D and E undergo recombination (Chiasmata between D and E). Here, $P_2=P'_{CD}\times P_{DE}=0.18$

If there is a chiasmata between both C and D, and D and E, the resultant will not have a recombination in C and E locus due to double crossing over. If there is no crossing over, there will be no recombination at either loci.

The net probability of recombination $P_{CE}$ will be the sum of these two, as any of these possibilities can occur to give a recombination between C and E. $P_{CE}=P_1+P_2=0.26$

And Biogirllajja, your calculation (the Edit) was almost correct, but you have to subtract $2$% from both $10$% and $20$%, because, both of them include the probability of crossover at one loci, including the case where the other loci has also crossed over. Hence, you need to subtract it from both, and then add to get $26$%. Tell me if you want me to expand on my explanation or provide some clarifications.

If we simply add the map distances, we get the actual map distance which disregards the possibility of double recombinations. All map units greater than 10cM have significant chances of double crossovers between them, and hence, the observed recombination frequency would be less than the expected 0.1. Hence, for distances greater than 10cM, the observed frequency of recombination will not be the same as (map distance/100).


Interpreting the reciprocal of $R_0$ $R_0$ is the average number of secondary cases arising from a single infectious individual in a fully susceptible population.

In many of the compartmental models for epidemiology, the parameter $\frac{1}{R_0}$ appears frequently.

In particular, in an SIS model, the non-trivial steady state is $(S^*, I^*) = \left(\frac{1}{R_0}, 1 - \frac{1}{R_0} \right)$.

  Is there any intuitive interpretation one can give to the reproductive ratio's reciprocal?

I'm thinking some sort of average rate of secondary cases, but this doesn't feel right since $S^*$ is a number.

1/R0 is the threshold fraction. If fraction of population vulnerable to particular infection is  more than 1/R0, only then infection can spread further. And if it is less than 1/R0 then infection can not progress and eventually goes away

And, 1-1/R0 is the fraction of population which requires vaccination so that we can have herd immunity.

(Reference
http://home.iitk.ac.in/~peeyush/mth426/Epidemiology.pdf

https://www.slideshare.net/singh_br1762/r0-value-herd-immunity)


maximum # of generations possible in a population of cannibalistic rats Assume a sufficiently large population of rats (to allow genetic variation and facilitate inbreeding) in a place with abundant water, sunlight, shelter but no food. For how many generations can this population persist solely by cannibalizing?

Here's a back of the envelope answer: one generation if you have a LOT of rats.

Numbers according to the Great State if Indiana.
Assuming also that we start with adult breeding rats.  50% females / 50% males.
The gestation period is 21 days.
The adult rat can eat 1/3 of its body weight each day. Assuming that the rat is eating about 80% of the 'victim' rat body weight, the colony reduces in size about 40% each day.

Lets say the rats are going to be a bit hungry and the colony loses 30% of its size each day. And they don't eat their own feces, which I think they can do, but also assuming that the malnutrition from eating only rat for food will not cause problems.

Over the period of gestation, 21 days the colony will have a final size of 0.3^21 = 0.000559 times its original size.  So in order to have a surviving gestating female you'd have to start with 1791 rats.  Also assuming that the last rat is a very pregnant female who can compete with the male cannibals who are not pregnant.

Then the average litter is not 1790. So you'd need something like 1790^N rats for N generations.  and they'd have to be pretty lucky rats to boot.

BTW similar numbers would be true for any animal including human beings. This is one reason that cannibalism is usually only a social ritual, not a means of acquiring nutrition except in extreme cases.


Why do apples taste sweeter at the bottom? Sometimes when eating an apple, I notice that the bottom (blossom) end of the apple has a lot more sweetness and flavour to it, whereas the top half (stem) is often more watery, crispier and feels less dense than the bottom part.

A quick search on the internet revealed that I'm not the only one asking this question, but answers seemed to be mainly opinions. The largest discussion I stumbled upon can be found here, but comes to no satisfying conclusion.
Apparently, this phenomenon seems to occur in pears (supposedly even mentioned in a japanese saying, but the article does not provide a solution to the question) and pineapples as well.

I am looking for a more scientific explanation, as I believe that the biology of apples might be more complex than to allow a simple "sugar is denser than water and gathers at the bottom"-solution.

Do apples ripen unevenly (the blossom-end growing first, allowing it to ripen for a longer time)?

Might this phenomenon be the result of how apples meant for long-term controlled atmosphere storage are picked slightly less mature?

For whether or not your assumption is correct, I have found the following (here), which states that sweetness indeed differs, as well as pH level:

  The bottom sections of ‘McIntosh’ apples were sweeter; whereas the bottom sections of ‘Jonagold’ were less crisp and more fruity.
  The bottom sections of both the ‘McIntosh’ and ‘Jonagold’ apples had significantly lower pH than the top.

Fruits consist of two main parts, the pericarp and the seeds. The pericarp can be further divided into the followings: exocarp, mesocarp and endocarp. In the case of apples, the one responsible for composing most part of the fruit flesh is the mesocarp, so I would like to disregard the other two. The mesocarp consists of ground tissue almost exclusively[1] and no vascular system, thus the only way for sugars to travel inside the flesh of fruit is diffusion, which is mostly determined by gravitation, hence the result.


Why do people feel pleasure when using roller coasters / centrifuges? The feeling when using an amusement park unit is usually a pleasure. Why is it not a pain instead?

Are there advantages, from an evolutionary point of view, in loving this potentially dangerous activity?

Is it related to the liking for extreme sports?

Riding roller-coasters usually (unless you are psycho) induces a release of adrenaline and other chemicals, like endorphin (your bodies pre-emptive effort to combat any possible pain and stress you may be about to experience), into your body. Endorphin is a strong chemical, specifically released to make you feel relaxed and confident. Obviously this explains the natural high you may get from riding a coaster.

However, every now and then you get that person who ruins it for everyone by having a heart-attack. This person's body was not conditioned for this type of stress, and clearly they did not enjoy their ride much. Elevated blood pressure,
erratic heartbeat and palpitations...they should have instead taken a ride on the log flume. For the rest of us thrill-seekers, this type of gung-ho, take-all-comers attitude gives us a confidence boost by wiring our brains to not be overly stressed in actual emergencies.

Imagine the people out there who have grown up in small towns. You may have heard how such people can have a difficult time adjusting to the hustle and bustle of city life, especially in larger cities. This has to do with everything from their metabolism and diet, to their sleep cycle. Their body simply needs to get used to the new environment. The same goes for new combatants. Military's try their best to simulate combat for new trainees. The better the simulation, the better prepared people will be for combat. The first few combat situations for people are obviously going to be the most dangerous, being a truly foreign experience for most peoples bodies.

Physiologically it's going to push your body to the limit. After all, you sense your life is in serious danger. But as many people deal with this stress, they can start to acclimate until they ideally stay fearful, but become extremely focused on the fight. The adrenaline rush (and again, other chems) is part of what you need to get used to. If your body has a naturally stable system when exposed to these chemicals, or you have trained it to be so, then you are at an advantage compared to your peers.

https://www.psychologytoday.com/blog/threat-management/201001/adrenaline-rushes-can-they-help-us-deal-real-crisis

http://www.faqs.org/health/topics/15/Risk-taking-behaviors.html


How do CpG islands remain unmethylated? In most of the genome CpG sites are pretty much always methylated, but CpG islands are instead often unmethylated. This has been linked to the fact that they often are associated to transcripted genes.

What are the current theories on the mechanisms involved in this preferential demethylation?

Methylation is increasingly seen as a consequence of gene activity rather than a regulatory mechanism. There are cases where methylation is controlled because of gene regulatory control, especially at the famous H19/Igf2 locus[1]. Here is a generally good recent review[2], note they mention that DNA methylation does not cause transcriptional silencing, and likely methylated promoters are probably more active than unmethylated, they just create silencing RNAs when methylated (resulting in an apparent silencing).  This may help explain some of the story[3], but note how old that paper is, yet generally I'd say few people know of its existance.

The exception seems to be transposable elements[4], but their control is probably also controlled by silencing RNAs.

References:

 Zampieri M, Guastafierro T, Calabrese R, Ciccarone F, Bacalini MG, Reale A, Perilli M, Passananti C, Caiafa P. 2012. ADP-ribose polymers localized on Ctcf-Parp1-Dnmt1 complex prevent methylation of Ctcf target sites. The Biochemical journal 441: 645–52.
 Deaton AM, Bird A. 2011. CpG islands and the regulation of transcription. Genes & development 25: 1010–22.
 Rountree MR, Selker EU. 1997. DNA methylation inhibits elongation but not initiation of transcription in Neurospora crassa. Genes & Development 11: 2383–2395.
 Bourc’his D, Bestor TH. 2004. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431: 96–9.


How do scientists discover a new antigen and its epitope? I've found some database on the internet that list all discovered antigens and their epitopes.
So how do scientists discover a new antigen? Do they try to inject them into the body to see if it causes an immune response or not? And finally if it's an antigen, how do they know their epitopes?

Okay, you have a few questions building on top of each other (rephrased the questions for clarity):

  How do scientists discover a new antigen?

There are multiple ways to this, which are applied for different purposes.

In order to discover a natural antigen, which is recognised by an antibody normally produced by the immune system, one would first have get hold of this specific antibody. This would be an approach to reproduce or understand the effective response of the immune system against a pathogen (e.g. a virus).

In order to get hold of the antibody (and ideally the coding DNA sequence for it), researchers have to use the pathogen, or parts of it and find the antibodies (or B cells) that bind to it. To do this the pathogen (particles) could be fixed to a column and after running blood through the column the respective antibodies and B cells will remain in the column. Then the DNA of these cells can be sequences, or the antibody can be further purified.

In most cases however, scientists want to find a not-yet existing antibody against an antigen, which leads us to:

  Do scientists try to inject antigens to the body to see if it causes an immune response or not?

Yes, this is done - but only with animals (mostly rats, rabbits & goats). Polyclonal antibodies can be extracted directly from the blood of these animals, but most often monoclonal antibodies are needed for research or medical purposes. The process required for these is much more complicated, but leads to a cell lines which can then be used to produce the desired antibody in greater quantities.

  How do scientists know the corresponding epitope to an antibody?

There are multiple ways to find the exact epitope of an antibody, all of which are commonly described as epitope mapping.

The most common methods are based either on site-directed mutagenesis of the antigen to see which positions (amino acids) are crucial for binding of the antibody, or on peptide fragments of the antigen, which can still be bound by the antibody.


Do antigens protrude through the capsule/slime layer in prokaryotic organisms where these features are present? In prokaryotic organisms that have a slime layer or capsule, do intrinsic/extrinsic proteins and other molecules that could be used as antigens protrude through the capsule?

I assume that they must in order to maintain their function for the cell, yet am struggling to suggest another way in which the presence of a capsule/slime layer could serve as a defence against phagocytosis?  Unless the slime layer directly resists lysosomal activity after the pathogen has been recognised and engulfed?

On a related note, could the flagella of an organism (which must protrude through the capsule as above) trigger an immune response on its own?

They don't have to -- there are times in life of a bacteria (cell division, hunger, mutations, attacks of lysozyme and other enzymes, cell lysis) when any possible antigen gets less or more exposed.

About escaping phagocitosis, there are numerous strategies to achieve it -- from forming a large slime-covered colony, through killing or disabling phagocytes up to stopping digestion, escaping the phagocyte back to the environment or even living inside it (Listeria monocytogenes is a prime example -- it can even directly move from one cell to another).
EDIT: Here is a nice overview.


Can any enzyme be produced? After reading about how recombinant insulin is produced, the following question occured to me. Does the current level of technology allow any enzyme to be produced in a similar way?

As I see, producing amino acid sequences is not an issue. A possible difficulty I can think of is modifying the amino acid chains. In the case of insulin the problem has been solved. Are there some generally applicable solutions available to this problem, or do they have to be researched on a case-by-case basis?

Are there any other limitations to producing enzymes?

EDIT: As pointed out by P. Jay, the question might seem to suggests that insulin is an enzyme which it is not.

No, not all enzymes (or other proteins for that matter) can be obtained in functional form by recombinant expression with today's methods. As you suspect, problems arise when complex post-translational modifications are necessary to obtain the correct function.

Direct modifications to peptide is one potential problem. Some of these can be resolved by expression the recombinant protein in the right cell type: for example, expression in a bacteria may not provide the right modification, but expression in yeast or a mammalian cell might. CHO cells are a common mammalian cell type used in such cases; antibody production in hybridomas is another well-known example. But there are plenty of posttranslational modifications that are poorly understood, and most likely there are still many completely unknown types; new ones are still being discovered.

Another posttranslational event is association with cell membranes. Membrane proteins (including membrane-embedded enzymes, for example in lipid metabolism) can be very difficult to express properly, as not only the peptide but some surround membrane structure must be reproduced in the expression system to obtain correct function. This is also a major hurdle in obtaining structures for membrane proteins, notably many cell surface receptors. This article is a summary of the current challenges and unsolved problems in this area. And you can imagine the problems with proteins that need to form large superstructures to be functional --- large protein polymers, respiratory chain complexes, ribosomes, DNA replication forks ...

So there is no universal method; all proteins are different, some are easy to express, some are extremely hard.


Self-fertile PRUNUS: Approximately how much of the genome gets rearranged by meiosis? I'll admit that I don't have a background in science, so this might be a stupid question. Suggestions and edits are welcome. The question is related to a similar question I had here: What DNA does a self-fertile plant's seedling have?

Some prunus plants are said to be partially self-fertile. An example is prunus tomentosa. I've been informed that through self-fertilization (a.k.a. selfing), meiosis occurs, which rearranges the genome.

  ...when selfing, meiosis is occurring (and therefore segregation and
  recombination) so that the offspring is not an exact clone of the
  parent but rather some kind of a rearrangement of the parent genome
  (with a few mutations of course). Source

Approximately how much of the genome of a self-fertilized seed is impacted by meiosis? Is a large amount of the genome rearranged, such as 25%? Or less than 1%?

It makes little sense to give a percentage of the genome impacted by recombination and segregation. I think you should read about segregation and recombination and that would be clear to you why giving a percentage makes little sense.

Segregation

Segregation causes that the two haplogroups of the parent can be rearrange at the among chromosome level. So, for example if, in this lineage, each individual has 3 pairs of chromosomes. Let's denote each haplogroup by a capitalize vs non-capitalize letter, we can represent the genome as

a|A b|B c|C

Without segregation (and recombination), a parent could only transmit either

a b c

or

A B C

in a given gamete. This results in the three possible zygotes

a|A b|B c|C
a|a b|b c|c
A|A B|B C|C

segregation allows the creation of gametes like for example

A b C

resulting in possible zygotes such as for example

A|a B|B c|C

Recombination

Recombination typically occurs at a rate of one recombination event per chromosome (that is 100 centiMorgan per chromosome as a rule of thumb; see here to understand what a centiMorgan is). Further rearrange creating new haplogroup from the two existing haplogroups. So for example, from the pair of chromosome

A|a

an individual could create a new haplogroup from recombining the end of A with the beginning of a (or vice-versa).

Related posts

There are probably a lot of related posts. Here are a few of them:

Do only one or both pairs of homologous chromatids exchange genetic material during the process of crossing over?
Gene distance and Recombination Frequency: Mechanism
Is the discovery of dominant and recessive genes the only reason Mendel matters?
What is Mendelian Segregation and how is it related to the Hardy-Weinberg equilibrium?
Genetic linkage greater than 50 centimorgans
What are the exceptions of Mendel's laws?


number of RNA pol II molecules in a given human nucleus? Does anybody have any estimate on the number of RNA pol II molecules in the nucleus of a given human cell? For example, how many RNA polymerase type II protein complexes would there be on average at a given time in, say, a human immortalized lymphoblastoid cell line (LCL)?

it is highly variable even in a single cell type.

Dont know for a human cell but this is the range for ecoli: 1500-11400

check this site out. got this number from there (its quite useful for questions like these):

http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=101440&ver=3&trm=RNA%20polymerase

You can estimate protein copy numbers and there are techniques available for doing so. One of such techniques:

http://www.mcponline.org/content/11/3/O111.009613.long

You can also calculate concentration using traditional techniques like western blot and elisa and calculate approximate copy-numbers (you have to also calculate average cell volume and number of cells for protein extraction.


Movement of sperm to the egg Sperm swims through semen and reaches the haploid egg in the oviduct during fertilisation.

Once the sperm reaches the cervix, through what does the sperm swim through to reach the egg?
Is the uterus completely filled with a fluid that allows the movement of the sperm, or does the sperm only swim through the endometrium (uterine lining)?

Once the sperm reaches the cervix, through what does the sperm swim
  through to reach the egg?

It swims through the cervical mucus. Human sperm swim in a straight path in cervical mucus.

  Is the uterus completely filled with a fluid that allows the movement
  of the sperm, or does the sperm only swim through the endometrium
  (uterine lining)?

Yes, the uterus is completely filled with uterine fluid. They are attacked by many leukocytes while being helped by various contractions.

I would suggest reading the Suarez 2006 review. It has very nice information of all stages of sperm moment.


How do burrowing animals get enough oxygen? Tree borers make a small hole in a tree. At the end of it, they chew on wood to elongate the tunnel. They digest food and grow. All this takes oxygen.
The entrance to the tunnel is generally small. Some borers plug the entrance. Even without that, air circulation must be non-existent. How do they breathe?
It just seems off hand that tree borers might be an extreme case. But I have the same question about all kinds of burrows. How do worms do it? Rodents? Ants?
Do burrowers have any special behaviors or adaptations to help them cope?

Thank you all for your answers and comments. But I suspect there is more to it than that. I doubt enough oxygen diffuses down the length of the burrow to keep an insect alive under bark.
A tree died in my yard recently. The bark now comes off easily. When a tree is stressed or diseased, insect often attack. They finish off the tree if the original problem doesn't. Clearly that has happened here. They have eaten almost the entire layer under the bark. No wonder the bark is peeling off. There is almost nothing left of the wood it was attached to.

Most of the burrows are long and narrow. The insects carefully leave a small strip of wood between adjacent tunnels.
Here is a close up of two burrows from the bottom of the previous picture. It was taken before I pulled off all the bark. You can see they started at the bottom, and grew as they climbed.

Here is the bark that covered the burrows. When insects chew the wood, the wood does not disappear. At the bottom you can see a portion of the sawdust that packed the burrow. Most of it fell out when I peeled off the bark. I have seen other pieces of bark where it clearly filled the entire burrow.
At the top, you can see the holes where they dug out.

Now that the tree is dead, the bark is falling off. But it wasn't when they started. Trees do not make it easy for insects to eat them. I expect the bark was well attached. I doubt it was porous enough for air to penetrate. I doubt there was damage, such as the long crack you can see along one burrow.
Sometimes wood can be surprisingly porous. You can literally blow smoke lengthwise through a plank of red oak. But that is cut and dried wood. Live wood is full of sap.
I expect that insects do not make holes in the tunnel. They make it hard for predators to get it.
And yet enough oxygen does get in.

A year later, I still think about this off and on. While having a small mass reduces oxygen needs, oxygen is needed to chew a tunnel in wood and grow. I cannot believe that enough oxygen diffuses down a long narrow tunnel packed solid with sawdust.
Here is a photo from when I burned a log from the tree. You can see the surface is covered with burrows. There are also holes into the interior.

Here I have split the log. You can see the holes continue deep into the tree and lead to chambers. These burrows are almost entirely free of sawdust.

Here is a detail view.

I expect they are kept clear because insects need to crawl down them. One reason would be they need air.
Yet the surface burrows are packed. It seems likely an insect that can chew tunnels in wood can poke holes in bark. Does anyone know if they do this?
One last thought. I heat my home with wood. When I carry firewood home, I store it under this tree. People tell me you can transport insects in firewood...

As the body mass of an organism decreases, their volume decreases with direct proportionality, so their metabolic needs are also reduced. The result is that small organisms like worms and insects have a much larger surface area to body mass ratio, which lets them passively transfer oxygen into their bodies much more easily.

I am by no means an entomologist but most species of insects are able to exchange gases with the environment without any active respiration at all. Due to their small size, gases can passively diffuse through the trachea and spiracles directly to their internal fluids/muscles.

That said, insects simply have much much lower basal metabolic rates compared to even small vertebrates. Lower metabolic rates mean lower oxygen needs, so that's why its not uncommon to see insects surviving in cracks and crevices that don't have a lot of air circulation. The little air circulation that does occur in the temperatures that insects thrive in is more than enough to support their oxygen needs.


What is the difference between clinical and non-clinical depression, and is there a term for different severity of the bipolar disorder? I was looking for a term which describes a bipolar disorder of lesser severity.

I know from experience from someone I know well, what a very severe case of the bipolar disorder looks like, when an otherwise very intelligent and very sane person can become completely unstable in both directions, and requires medication to basically survive it.
I'm searching for a term which has indeed the symptoms of the bipolar disorder, but is not as severe as to require medication to basically survive the mood swings. I'm not talking about being just sad for something or craving attention. I'm talking about the very real symptoms of mania, followed by depression, just not as severe to be fatally dangerous without medical intervention. A severity which I would describe of being able to cope with by learning about it and a good degree of self-control, exercise, and good eating habits.

I thought the term was clinical versus non-clinical depression, but a search of the Internet made me doubt it. They talked about it as if the clinical was a case where there is a "disorder of the brain" and the non-clinical was "just sad because of a sad event", so either were those forums wrong (I guess so, because of their apparent unprofessional writing style, and they never seemed to know about bipolar, they thought manic depression was just about being very very sad), or there is another term which best answers my question.

I think the main question here is:

  Is there a term…which describes a bipolar disorder of lesser severity[?]

Yes. There are a couple ways to think about this, but you’re clearly accustomed to differentiating the manic and depressive phases of bipolar disorder, so I’ll start with that.

There is mania (excerpted from DSM 5*):

  A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy, lasting at least 1 week and present most of the day, nearly every day...

  B. During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms (four if the mood is only irritable) are present to a significant degree and represent a noticeable change from usual behavior:

  Inflated self-esteem or grandiosity.
  Decreased need for sleep
  More talkative than usual or pressure to keep talking.
  Flight of ideas or subjective experience that thoughts are racing.
  Distractibility
  Increase in goal-directed activity
  Excessive involvement in activities that have a high potential for painful consequences

  C. The mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning....

And there is hypomania:

  A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 4 consecutive days and present most of the day, nearly every day. ….

  B. [This criteria is the same as for mania.]
  ....
  E. The episode is not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization.

I have bolded the main differences between the two definitions. You can see that hypomania is the term for the less severe form of the manic phase of bipolar depression.

Neither mania nor hypomania is likely to occur in the absence of depressive symptoms, however. Thus, there are two basic phenotypes of bipolar disorder (summarized from DSM 5*):

Bipolar I disorder: Patient experiences mania; depressive periods may not qualify as Major Depressive Disorder.

Bipolar II disorder: Major Depressive episodes are required; manic phase may be hypomanic. (This is classically considered a less severe syndrome, but this notion has been challenged in recent years.)

And finally, one more term for you:

Cyclothymic disorder: patient experiences both hypomanic and depressive periods without ever fulfilling the criteria for an episode of mania, hypomania, or major depression.

(Your other question you seem to already know the answer to, but since it's in the title.....  Nonclinical depression refers to something on the spectrum of normal (i.e. not pathological), such as situational mood disturbance. A related concept, subclinical depression is a loose term to describe depressive symptoms that don't meet criteria for Major Depressive Disorder..)

*American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.


What is the real meaning of the statement "*ontogeny recapitulates phylogeny*"? I tried searching in this site but couldn't find an appropriate answer to the title question: what is the real meaning of the statement "ontogeny recapitulates phylogeny"?

Actually, the statement "ontogeny recapitulates phylogeny" has been largely discredited in modern biology.  The stages of embryonic development were thought by Ernst Haeckel to resemble ancestral species in evolution.  That is, early embryos appeared to have tails and gills and resembled fish, later embryos resembled quadrupeds, and so on.

However, embryos do NOT actually resemble adults of ANY species.  More accurately, one could say that early embryos of different species resemble early embryos of other species, and later stages differ more and more as specialized traits of different species become more obvious.  On the early extreme, one fertilized ovum shows very little difference in gross appearance from any other fertilized ovum, and the blastula of different species look very much alike, but as different organs and limbs become better developed, those of different species begin to look more and more different.

This actually only describes SOME of the changes that occur in embryonic development.  Other changes are not so simple.  One very good book that discusses the strengths and weaknesses in this area is the book "Ontogeny and Phylogeny" by Stephen Jay Gould.


Species identification please - Bug is a plague for Italian Stone Pines (Pinus Pinea) They hangout on the top of Pinus pinea and spray a sticky substance all over the place. Size is about 2mm (head and abdomen) may be 4mm including antennae and legs. Could you please help me identify it and understand some of its habits and biology? I took the photos in a coastal town in Southern Spain. Thanks!!

That's and aphid (Hemiptera:Sternorrycha). Most likely, it belongs to the genus Cinara, which is common on trees. https://en.wikipedia.org/wiki/Cinara


Why can myopic eyes focus on nearby objects, but not on distant ones? In myopic eyes, far away objects get blurry. I understand that myopia means that the focus of the lenses concentrates light at a point in front of the retina, thus by the point the light rays reach my retina they've already spread apart so they aren't coalescing on the same point as they ought to.

My question is, why is it that this deficiency only apparently manifests itself when things are far away?  Why is it that the focusing of light in front of the retina doesn't cause the same blurry vision up-close as it does far-away?

There are four common refractive errors, namely nearsightedness (myopia), farsightedness (hyperopia), astigmatism (Fig. 1) and presbyopia.

Fig. 1. Refractive errors. source: Excimer Ophthalmologic Clinic

myopia (nearsightedness): The eye ball is too long, or the cornea too steep, causing light to focus in front of the retina and making distant objects appear blurry.

hyperopia (farsightedness): The eye is too short, or the cornea too flat, causing light to focus behind the retina and making near objects appear blurry.

Astigmatism: is caused by an irregular cornea or lens, causing images both near and far to be distorted or blurry.

Presbyopia: a common age-related problem that is caused when the natural lens in the eye loses its elasticity, making it difficult to focus on near objects (hyperopia).

Focusing of the retinal image is mainly regulated through the process of accommodation (Fig. 2). Accommodation is mediated mainly by changes in the shape of the lens. A more globular lens results in a larger refraction of the light to focus on near objects. A flat lens refracts light less and is suited for focusing in the distance.

The lens is held in place by the suspensory ligaments. The ligaments in turn are attached to the ciliary muscle (Fig. 2). When the ciliary muscle contracts, it shortens. This effectively moves it closer to the lens and so any tension in the suspensory ligaments is released as the ligaments go slack.  Slack ligaments mean the lens adopts a more globular shape.

When the ciliary muscle relaxes, this changes its position to increase the tension in the suspensory ligaments. Taut suspensory ligaments (caused by the relaxed muscle) will pull the lens into a long thin shape.

Fig. 2. Accommodation. source: PMG Biology

In the case of myopia, objects in the far distance are blurry. Objects far away tend to send near-parallel light rays onto the lens and the lens needs to be maximally flat and hence the ciliary muscles should be maximally relaxed. If in this case the image is still in front of the retina, the lens cannot relax any further and hence the image is blurry. Because there is enough dynamic range for the ciliary muscles to contract, there is not any problem with objects close by, because the lens is perfectly capable of assuming a concave (fat) shape.


Does Lucid Dreaming decrease the regenerative effect of sleep? After watching this SciShow video on sleep, I wonder about lucid dreaming.

Specifically: Does lucid dreaming and associated directed agency within Lucid Dreaming decrease the regenerative effect of sleep?

That is, if I gained the skill of lucid dreaming - would I be negatively tampering with the brain's autonomous healing processes for the period that I had conscious control or even simply objective awareness during sleep?

It's possible that they do, depending on the intensity of the dream and the amount of brain activity.

For example, if the dreamer is thinking too much or is having a dream that's way too intense, the brain activity goes up and they're not as rested.  However, lucid dreaming can be good for sleep if the dreamer creates a more relaxed dream.  This can possibly be better for the sleeper, especially if they're someone who experiences nightmares every night.

Basically, it just depends on what you're dreaming about.  The calmer and more relaxing the dream is, the better.

Source:
-www.world-of-lucid-dreaming.com


Isolating gene of interest from a large strand of DNA I was always confused about this in class and never learned it fully.
So say you have 10,000 bp of DNA and you just want to isolate 100bp of specific region(gene of interest) using restriction enzyme.

How can you ensure that at the both ends of your gene of interests has the right sequences for certain restriction enzymes to cut.

Assuming that you know exactly where in the full DNA strand the gene of interest is located, it is fairly easy to isolate the gene. There are several restriction enzymes you can use, it's just a matter of determining which one(s) are most appropriate for your gene of interest.
Remember that it is usually fine to have extra nucleotides on either end of the gene; the ribosomes will start and stop adding peptides based on start and stop codons, independent of how far the ribosome moves before reaching the start codon. Analyze your DNA strand and try to find a restriction enzyme that will slice the strand somewhere before the gene begins, and usually another that will slice it somewhere after it ends, although sometimes the same enzyme will work for both ends of the gene.
Edit: As @Untitpoi mentioned, if the restriction enzyme's slice sequence is found within the gene of interest, it will cut your gene in two (or more). It is very important to ensure that the enzyme(s)s you choose do not slice the gene of interest, otherwise the strand will be useless. It's possible to re-join the strands (which, thanks to sticky ends, isn't too difficult), but why take the extra effort when you don't have to?


L1 - L5 layers of the brain I have read in some papers about the layers L1-L5 of the brain (e.g. in this paper). I could not find a definition of these layers. I have found information about the layers V1-V5 in the visual cortex.

Where exactly are L1-L5? And do these definitions vary across mammals?

V1-V5 are different (sub) regions of the visual cortex itself.

via http://www.tecsyn.com

The layers L1-L5 (some regions have a layer 6) refer to the different cellular strata in the depth dimension of the cortical mass.  This stratification occurs to some extent or another in various areas.  Different sections of the cortex, e.g., the primary motor cortex have a predominant level 5 (for the pyramidal tract).  Something like the visual cortex has more cells in layers 4 and 6.

 From http://www.unige.ch/cyberdocuments/theses2003/RivaraC-B/images/fig.2.jpg

Layers 2 and 3 tend to carry interconnections between different areas of the cortex, and the topmost layer is generally less dense.


tandem repeat sequence; causes of contraction and/or expansion question Question:

Which of the following events, occurring within a tandem repeat sequence, will cause an expansion or contraction of the array?

A) Endoduplication    B) homologous recombination    C) Unequal
   crossing-over   D) Error-prone DNA repair    E) Inversion

I know for a fact that upon replication, tandem repeats of DNA (specifically trinucleotide repeats) can form loops which are repaired by mismatch repair enzymes (MSH2-MSH3); and failure to correct this would lead to an expansion of the array post-replication. However, this answer was incorrect.

Could someone assist me with this question? I read up on the topic but its not clear to me why DNA repair defects do not suffice as an answer. I don't also necessarily understand the correct answer (C)

Thanks so much

-Chris

Gene-duplication would not result in contraction (only expansion). Endoduplication would affect all the genes in the chromosome. Error prone repair would cause small-indels but not expansion of the repeats. Inversion will certainly not do anything to the sequence except changing its orientation.

During unequal crossover, the chromosomes can align imperfectly because of multiple alignment sites in the repeat region, thereby leading to unequal crossover products.  Crossing over however essentially happens because of homologous recombination. Crossover is a "phenomenon" and not a "mechanism" in a true sense.

  Mechanism of crossover

  Reproduced from: Bugreev, Dmitry V., et al. "The resistance of DMC1 D-loops to dissociation may account for the DMC1 requirement in meiosis." Nature structural & molecular biology 18.1 (2011): 56-60.

Another thing to note is that homologous recombination in the absence of crossover can lead to expansion of repeats but not contraction (see below).


What is the purpose of the outer mitochondrial membrane? The purpose of mitochondria is to generate ATP, utilising a chemiosmotic gradient across the inner mitochondrial membrane. Protons are pumped out of the mitochondria into the intermembrane space, but because the outer mitochondrial membrane is highly permeable to ions, the pH of the intermembrane space quickly equilibrates with the rest of the cell. As the outer membrane apparently does not contribute to maintaining this chemiosmotic gradient, what is its purpose? It seems to be doubly redundant in chloroplasts as H+ transport doesn't even occur across the inner membrane.

Structure origins

Originally the mitochondrial outer membrane (MOM) was likely the result of a bacteria that could survive in a vesicle formed of the plasma membrane.

This explains why the plasma membrane and the MOM are structurally similar, however, the proteins that are present in either mean that their functions are very different.The MOM has a specialised translocation complex for example.

Functional significance.

The MOM is actually much more complex than an evolutionary hangover and is essential to modern cells by regulating what that mitochondrial inner membrane is exposed to. The MOM plays this role using porins. Indeed, if the porins of the MOM are disrupted, the entire cell dies (Chipuk et al, 2006). Additionally, the MOM allows a physical association between the ER and the mitochondria called the mitochondria-associated ER membrane (MAM). The MAM is essential for $ {Ca}^{2+} $ transfer.

  The MAM thus integrates signal transduction with metabolic pathways to
  regulate the communication and functional interactions between the ER
  and mitochondrion. (Hayashi et al, 2009)

Answer: The MOM is essential in regulating what the MIM is exposed to, and allows signalling between the ER and mitochondria.


Speed of Brain Waves Given that brain waves are characterised as such by virtue of the wave-like properties of 'electrical activity' in the brain, what is the speed of such waves; and how does it differ from neural conduction rates in peripheral nerves ordinarily in the range ~50 cm/sec.  (Oddly I have had difficulty locating an answer to this question elsewhere).

Unfortunately the term "wave" is ambiguous in neuroscience. What you are referring to, alpha waves, only means that neuronal activity tends to oscillate at about 10Hz. Neural oscillations are a widespread phenomena occurring in all brain areas. But it doesn't necessarily mean these waves travels. There are examples of traveling waves, whose speed can vary a lot (from $10^{-1}$ to $10^{-5}\ m.s^{-1}$ depending on the studies). Oscillations across brain areas tends to be synchronized during a task (so one could argue, infinite speed), and within area activity tends to hold a specific phase relationship which varies spatially (as if a wave was "frozen", in which case its speed would be 0). Traveling waves and neural synchrony/coherence might be different phenomena implementing different functions. It is still unclear what brain oscillations are for, or even if they have any purpose at all. Below are some reviews on these topics.

Ermentrout, G.B. and Kleinfeld, D. (2001) Traveling electrical waves in cortex: insights from phase dynamics and speculation on a computational role. Neuron 29, 33–44

Sato, T. K., Nauhaus, I., & Carandini, M. (2012). Traveling waves in visual cortex. Neuron, 75(2), 218-229.

Engel, A. K., Fries, P., & Singer, W. (2001). Dynamic predictions: oscillations and synchrony in top–down processing. Nature Reviews Neuroscience, 2(10), 704-716.

Fries, P. (2005). A mechanism for cognitive dynamics: neuronal communication through neuronal coherence. Trends in cognitive sciences, 9(10), 474-480.


What is this black insect (wasp-like?) South America? I live in the Pacific coast of South America. Seems to have two wings, like a wasp's. The "tail" is a bit bulky but is only connected to the rest of the body by a thin part. It's black overall. The antennae in the photo are downwards but they just spring normally to the front...

Actually I took photoshop to help me find this little guy, Ensign Wasp(Evaniidae)

Google Images:

My Photoshop research:


Could alcohol be used as an antibiotic? I was thinking about how alcohol is used to sterilize, and I was wondering if it would be possible to use alcohol as an antibiotic? if it kills bacteria, couldn't (conceivably) alcohol in the bloodstream kill any bacteria there, and the alcohol would be cleaned out by the liver later? Or would the concentration of alcohol necessary be too high and cause poisoning?

Sorry if this has an extremely obvious answer, but all of the results I found in Google were about drinking alcohol while on antibiotics.

Could, in theory, alcohol (delivered in any way) be used as an antibiotic? If so, how? If not, why?

No.  The CDC recommends using a hand sanitizer at at least 60% ethanol.  Most preparations used in the lab are 70% ethanol.  Humans start to risk death somewhere around the 0.3% alcohol level (BAC), especially around 0.5%.  People have gone higher, but even 1% BAC would be completely useless against bacteria.  You'd be dead long before the bacteria died.  Besides, if you've got bacteria in your blood, you've got bigger problems than a simple infection.

In a pinch, though, it can be used as a topical antiseptic, as per this fun article.


What is this salt-water worm? We found this near Fort Pheonix in Buzzards Bay in Massachusetts. It gets long when its swimming (About 8 inches) and contracts when disturbed (2 inches).

Its head is shaped a bit like a diamond (like a cobra?). Its body looks fairly translucent and is ribbon-shaped.

Here's a short video: https://vimeo.com/240322590

It is possibly a milky ribbon worm (Cerebratulus lacteus).

source:  intertidal-novascotia.blogspot.com

They can be found anywhere and everywhere along the Atlantic coastline in healthy abundance - http://intertidal-novascotia.blogspot.com/2012/05/cerebratulus-lacteus-milky-ribbon-worm.html


Why don't McDonald's fries decompose? So I was cleaning out my car and found a McDonalds French fry. as I don't eat anything in my car I know exactly who and when this fry is a result of. The when is + 10 months old and it could pass off as one just prepared. How could this be?

This controlled experiment of burger decomposition explains in detail why fast food burgers do not decompose easily. The same can be applied to fries, which are smaller and come dehydrated from the frying.

The main take-aways from this experiment are:

1: Dehydration is the main reason why fast food fries/burgers do not decompose easily. Placing the burgers in a ziplock bag, preventing dehydration, causes the burgers to decompose.

2: Since an unsalted, home-made burger did not decompose, preservatives, chemicals, saturated fats, and other components are unlikely to be the case of the fast food burgers not rotting.


Could a fetus properly develop in micro/zero-gravity? I suppose another way of looking at the question is: how important is gravity for the development of mammal fetuses?

And if things would go wrong, what sort of things would they be, and what would be the result?

There is some evidence that fetal development under zero gravity conditions might be problematic.

  Wakayama S, Kawahara Y, Li C, Yamagata K, Yuge L, et al. (2009) Detrimental Effects of Microgravity on Mouse Preimplantation Development In Vitro. PLoS ONE 4(8): e6753. doi:10.1371/journal.pone.0006753

The paper is here.

These authors studied aspects of reproduction of mice in a clinostat under 10-3G. They found that fertilisation was unaffected, but that preimplantation development of the embryo was affected by the mG environment.

The introduction to the paper gives a good brief review of this area of research. Perhaps of particular relevance is this section:

  In the STS-80 space shuttle mission, mouse 2-cell embryos were collected on the ground, launched into space and cultured for four days in µG. The control embryos on Earth developed to normal blastocysts, but in the space flight group, none of the embryos showed any sign of development, and all degenerated (Schenker & Forkheim, 1998) . A more reliable experiment was done on the Cosmos 1129 mission in 1979, when mature male and female rats were sent into orbit and then allowed to intermingle in a common breeding chamber (Serova & Denisova, 1982). However, none of the females gave birth, although postflight examinations revealed that ovulation had occurred. Two of the females were reported to have achieved pregnancy, but the embryos appear to have been resorbed.

Schenker E, Forkheim K (1998) Mammalian mice embryo early development in weightlessness environment on STS 80 space flight. Israel Aerospace Medicine Institute Report.

Serova LV, Denisova LA (1982) The effect of weightlessness on the reproductive function of mammals. Physiologist 25: S9–12.


What type of fish is this and why is it so big? This is a screenshot from a youtube video that you can watch here:

https://www.youtube.com/watch?v=zcdJNPYkIE0

That is a Queensland Grouper (common name).


Why does Helium make your voice change? When we breathe in helium and then speak, our voice changes drastically. Does it happen only due to helium or can happen if we use other gas? What factors of the gas does our voice depend on (like density, temperatue etc.)

Helium is not as dense as air, and when your vocal cord vibrate with the helium, it vibrates at a higher frequency, making your voice higher. sulfur hexafluoride Is Denser than air, making your voice deeper.


Similarity between a heart attack and a spasm When someone is having a heart attack, could it be considered , in some situations, a spasm? Below, I have written how I believe the process may work.

The heart is basically a muscle working constantly to create a sinus rhythm. As I understand it, one can get muscle spasms in any muscle (correct me if I'm wrong). If so, then couldn't someone get a muscle spasm in a part of the heart muscle that disrupts the sinus rhythm and causes chaotic signals? Thus causing a spasm throughout the muscle.

When one is having a heart attack, does the electric shock used cause a dramatic and fast 'stretching' of the heart muscles allowing the heart to get over the spasm and back to normal rhythm? Could something else, like an ElectroMagnetic Pulse be used to 'stretch' the heart muscles away from the spasms?

I was able to do some reading and research and I found some interesting information that was a). news to me. And b). the answer is yes... And no.

A spasm can be the cause of a heart attack by causing the coronary artery to contract. When that artery contracts, it causes a dramatic decrease in blood flow to the heart. When the heart looses access to oxygenated blood it can cause chest pain (angina) or even an MI (Myocardial Infarction a.k.a. a heart attack). This spasm is can be caused by exposure to extreme cold, smoking and the use of certain recreational drugs.

However, this type of spasm cannot be stopped with defibrillation. Treatment for these involves administering Nitroglycerin and then later treatment involving Statin drugs and such.

In the terms you are speaking of, I don't see that that would be quite accurate. The most common cause of sudden cardiac death is VF (Ventricular Fibrillation) which is essentially an uncontrollable quivering of the heart muscle. I've never heard this described as a spasm though. Google searches of spasm and heart spasm have all lead to definitions of the word spasm and the coronary artery spasm mentioned above.

However, within that, I think you have a valid point and a decent understanding of how things work, just perhaps not fitting under the definition of a spasm.

When a defibrillator is used, it delivers a measured electrical shock to the person's heart and hopefully stops the chaotic electrical rhythm. I'm not sure if this part is correct however, I do not think you should look at that as a stretching of the muscle though. It is an electrical intervention that interrupts the former rhythm and hopefully the heart "forgets" what it was doing and returns to a sinus rhythm.

So, to summarize: A heart attack can be caused by a spasm; however, defibrillation does not help that type of attack. A defibrillator does not 'stretch' the heart but rather interrupts it's former rhythm. Because an irregular heart beat is not considered a spasm, I find it difficult to believe that any form of EMP would help it; however, I would love to hear that it has!

For more information on Ventricular Fibrillation, CAS (Coronary Artery Spasm) and AED's (Automated External Defibrillator(s)). Please see the following:

MedlinePlus - on V-fib

The Mayo Clinic - on CAS

HeartSine - on AED's

I hope this was helpful for you!

Edits:

In the comments, we had discussed a variety of possible causes and treatments for spasms, as well as what - if any - connection there is between how a spasm in perhaps a leg would be caused as compared to how one in your heart could be caused.

From the reading and research I did, I was fairly inconclusive about the safety or desirability of a device to prevent heart attacks using an EMP device implanted in your brain or on your brain stem.

As far as how similar a spasm in your heart is to a spasm in any other muscle, they are not very similar. As seen here, a muscle spasm in most parts of the body can be caused by numerous things, such as dehydration, poor blood circulation, mineral deficiencies etc. Whereas a heart spasm (know as a CAS) can be caused by alcohol withdrawal, stimulant use, extreme cold... As seen here.


Possible combinations in the Meiosis' Telophase 1 As you might already know

  Meiosis is the process in eukaryotic, sexually-reproducing animals that reduces the number of chromosomes in a cell before reproduction $^{[1]}$

One of the reasons why meiosis has been so important in evolution is variation.

As my teacher used to say: Nature rolls the dice... - It's the magic of genetics; two completely different persons might share the same parents.

So here the question:

Suppose we have a cell with four chromosomes (two couples of homologous chromosomes) in the Prophase 1. I've drawn all possible combinations that could happen - these are chosen randomly - in the Telophase 1.

  Is there a genetic disorder (not only regarding humans), in which the four initial chromosomes are split, in the Telophase, into two parts, each of them containing a couple of homologous chromosomes. I.e. (referring to the image) is the combination $(\color{red}{red}+\color{blue}{blue})(\color{green}{green}+black)$ in the Telophase 1 possible?

$$$$
$^{[1]}$ Quote from https://biologydictionary.net/meiosis/

Failure to properly separate homologous chromosomes during meiosis, either by including an extra copy of a chromosome or including zero copies of a chromosome, causes gametes that are 'aneuploid', and as a result, a zygote that results from that gamete will have an extra or missing chromosome as well.

For humans, most aneuploidies are completely fatal at some point of early development, so there is not an associated genetic disorder in live births.

One common aneuploidy that is not fatal to the embryo is an extra copy of chromosome 21; this causes Down syndrome.


Can pymol show cartoon (secondary structure) for a pdb of multiple frames? I am using pymol to visualise the secondary structure of protein using its cartoon representation. The pdb file comes from a simulation, which contains multiple frames. After loading the pdb, its secondary structure (e.g. sheet, helix) could not been recognised. Surprisingly, if only one frame is kept, its secondary structure could be seen. So how to enable secondary structure recognition for a pdb file with multiple frames?

An example of the pdb file with multiple frames is shown below.

REMARK    GENERATED BY TRJCONV
TITLE     Protein in water t=   0.00000
REMARK    THIS IS A SIMULATION BOX
CRYST1  116.453  116.453  116.453  90.00  90.00  90.00 P 1           1
MODEL        1
ATOM      1  N   ASP     1      85.582  59.777  48.367  1.000.0000           N
ATOM      2  H1  ASP     1      84.882  59.067  48.507  1.000.0000           H
ATOM      3  H2  ASP     1      85.162  60.617  48.747  1.000.0000           H
... ...
ATOM   6615  OT  ALA   442      28.032  36.877  69.157  1.000.0000           O
ATOM   6616  O   ALA   442      30.092  36.087  68.677  1.000.0000           O
ATOM   6617  HO  ALA   442      30.072  35.867  69.597  1.000.0000           H
TER
ENDMDL
REMARK    GENERATED BY TRJCONV
TITLE     Protein in water t= 1000.00000
REMARK    THIS IS A SIMULATION BOX
CRYST1  116.384  116.384  116.384  90.00  90.00  90.00 P 1           1
MODEL        2
ATOM      1  N   ASP     1      75.052  41.097  56.132  1.000.0000           N
ATOM      2  H1  ASP     1      75.622  41.407  55.352  1.000.0000           H
ATOM      3  H2  ASP     1      75.602  41.357  56.932  1.000.0000           H
ATOM      4  H3  ASP     1      74.682  40.167  56.272  1.000.0000           H
ATOM      5  CA  ASP     1      74.032  42.157  56.202  1.000.0000           C
... ...
ATOM   6615  OT  ALA   442      45.292  49.247  90.922  1.000.0000           O
ATOM   6616  O   ALA   442      47.102  49.617  89.632  1.000.0000           O
ATOM   6617  HO  ALA   442      47.662  49.327  90.342  1.000.0000           H
TER
ENDMDL

It seems that if no HELIX record is present in the PDB, PyMol attempts to assign secondary structure itself. For whatever reason, it does not do this if multiple MODELs are present. You should be able to use the dss command to force PyMol to calculate secondary structure in a PDB with multiple MODELs.


If all B cells are present at birth, why should the primary response to an infection take longer than the secondary response? When learning about the immune response, my teacher mentioned that all the bodies B cells are present at birth, and there is one to counter every disease. But if this is the case, why should the primary response take a long time?

As far as I know, the primary response involves the non-specific response followed by the specific response, where APCs cause the activation of T cells resulting in clonal selection and expansion of T and B cells. The B cells then differentiate into plasma cells and produce antibodies. It results in the memory cells being produced, which can quickly reengage the specific response the next time the pathogen enters.

Why doesn't the body just make memory cells to begin with? As if it has already encountered every possible pathogen. I presume it is just a lack of specificity in the A level teaching, but I am curious to know what I am missing here.

Thanks,
Jamie

These so called virgin B-cells (becase they never had contact with their antigen) which are present in your body only have random B-cell receptors (when secreted, these are the antibodies), mostly of a relatively low binding affinity. These B-cells undergo division, re-arrangement and somatic hypermutation of the B-cell receptor and clonal selection. Only cells producing high-affinity antibodies survive this selection process and build later the pool for the memory cells and the plasma cells. It is like in the image below (from here):

Using this approach we have a big pool of low affinity antibodies (which somewhat fit). These are then used as the basis for the elaboration of a population of high affinity (perfectly fitting) antibodies, which target only the pathogen. And the antibodies are available relatively fast.


Mechanisms of bone growth The length of a bone is caused by growth of hyaline cartilage which is then replaced by bone tissue. How do cells know whether they should grow the hyaline cartilage? What are the key molecules that trigger the synthesis of hyaline cartilage?

How do cells know whether they should grow the hyaline cartilage?

Both growth factors and cytokines are involved but the trigger mechanism is unclear [1].

Bones grow in length at the level of epiphyseal plate where chondrocytes produce hyaline cartilage which by addition of calcium and phosphorus ions turns into hard bone [2].

It is believed that the growth process is under the regulation of local mediators like cytokines and growth factors:

  In recent years, a large number of cytokines have been discovered and their molecular structures and biological activities described. A surprisingly large number of cytokines have been shown to affect skeletal tissues, at least experimentally, making this a complex topic, but one which is furthering knowledge of how the cellular events of bone growth may be so precisely regulated [3].

References

Ossification. (2014, July 3). In Wikipedia, The Free Encyclopedia. Retrieved 15:47, September 30, 2014, from http://en.wikipedia.org/w/index.php?title=Ossification&oldid=615387908
http://www.personal.psu.edu/staff/m/b/mbt102/bisci4online/bone/bone5.htm
J.S. Price, B.O. Oyajobi and R.G.G. Russell. The cell biology of bone growth. Available from http://archive.unu.edu/unupress/food2/UID06E/UID06E0U.HTM


Amino acid substitutions near the receptor binding site HA protein in type A H3N2 influenza strains? I have read the scientific paper, "Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution" by Björn F. Koel et al (http://science.sciencemag.org/content/342/6161/976).

In the paper, important positions to influenza antigenic drift include positions 109-301, with special emphasis on sites 133, 144, 145, 155, 156, 158, 159, 189, 193.

However, nowhere in the paper does it specifically mention which positions are part of the receptor binding site and which are close to it.

The range (109-301) is a bit broad since it includes amino acid positions that are unimportant to antigenicity. I would like a list of all very important AA substitutions (that are near the receptor binding site) to involve in a bioinformatics project. The special emphasis amino acid sites list does not include all amino acids that are near the binding site.

To convey a sense of the problem, if position 155 is important, does that mean position 156 is also important?

I don't know if position 156 is considered "near" the receptor binding site.

Any help is appreciated.

Short answer: Yes, 156 is generally considered "near" the RBS, e.g. in this paper you can see it mapped onto the structure.

For a more general answer, you'll need to sit down and stare at 3D models of hemagglutinins (there are hundreds in the PDB), just like the rest of us. Antibody binding sites are not black and white, and interactions between influenza and antibodies are wildly complicated. What's "near" in some contexts might be "far" in others.

You might find the Influenza Research Database's Identify Sequence Features in Segments tool useful, particularly its annotation of hemagglutinin H3.

Be aware that numbering of amino acids can be confusing, since different groups may be using different starting points. There's a vague agreement on the "correct" numbering, but quite a few groups pay it lip service and then number their version however they like.


What disease / parasite / fungi has affected the mango in the picture? The mango is found to have some kind of fungi / worm on it's surface . This has affected a huge number of mangoes in the same tree . It can be described as white and fibrous / weblike structure near the top of the mango .

If you zoom in on your picture, you will see that the small orange blobs have legs. These are red spider mites (Tetranychus urticae), which is a very common pest species of plants world-wide. They are called spider mites as they may spin webs on the plants they are feeding off. You have quite the infestation in the picture. It will take quite a bit of pest control to get this under control. I suggest spraying with Neem oil.
The mites feed by puncturing the cells of the plant they are feeding off and sucking the cytoplasm out. This puncturing results in damage to the plant, which might cause invasion from a bacterium or fungus. In your case I would guess a fungus, probably a sooty mold. Sooty molds grow on sugary excretions from parasitic animals (like spider mites) or on secretions from the fruit itself.


Why are these ants moving as a pack? Recently I took this shot of a 'pack' of ants moving towards some destination, and I was wondering, is this normal? Aren't ant scouts lone wolfs, and when a viable source of food is found near the ant colony, the worker ants form a trail to facilitate transport? If so(I'm poorly versed with biology as such, being an electrical engineering student), what purpose could this formation serve, my opinion being bent on supposed predator protection. This is not the only one I've noticed, but it is new to me, and a quick google search without any technical terms to feed it, yielded nothing substantial. This is the monsoon season here in India, if it is of any consequence to this peculiar behaviour.

I'd love to found out more about this(tag edits would be helpful), thank you :D

This is a really wonderful phenomenon. Ants disperse far and wide, but when one of them finds food, it brings it back to the nest, and in doing so leaves a pheromone trail. The next scout follows this trail, and finds the food, and then leaves a second pheromone trail over the first one. As this continues, the trail gets stronger and recruits new ants to haul off the bounty. You can have fun with this. Take your finger and rub across the trail to erase it. Or place a piece of tape over it. This will confuse the ants for a while, until they make a new pheromone trail. If you have some time, break up a potato chip, or some other bait, and put it on the cement. Watch the first scout find it, and then leave a trail behind. Soon there will be many.


ID Fish from Florida? This fish was caught in St. Augustine, Florida. What species is it?

Looks most likely to be a Gulf Toadfish, Opsanus beta, judging from its size, location caught, and other similar identifying features.

More detailed species information at:
Opsanus beta on FishBase.org


L-selectin in white blood cells The white blood cells' function is mainly to fight off external antigens. However, another one of its traits is its ability to bind to vascular endothelial cells with the help of L-selectin. What is the purpose of this, and how does this help us？

Fighting of harmful microbes (and not antigens per se, although specific antigenic recognition is important), involves a lot of processes which require several lignad-binding molecules and ligands on the WBC surface. While the whole array of these proteins and their functions is very complex, we can take the case of a neutrophil trying to defend the body against microbes in a local wound, the so-called acute local inflammation response.

1. Adhesion to the endothelium

Here is where several selectins play a role. The simple broad idea is that in presence of microorganisms, as sensed by the local immune cells (tissue macrophages, blood cells in case of a vessel breach etc), there is an upregulation of chemokines in the local environment which causes the endothelium to increase the expression of certain adhesion molecules (ligands with receptors on WBC and vice versa) as well as other hemodynamic changes causing the neutrophil to come in close contact with these in the vicinity of the wound and bind to the endothelium. This is ften subdivided into three processes, margination, rolling and adhesion. L-selectin is one of these adhesion mediators, along with other selectins and integrins.

2. Migration through the endothelium into the tissues (diapedesis)

3. Chemotaxis towards microbes

4. Action on the microbes

Points 2,3 and 4 have their own mediators (see CD31, chemokines - AA, C5a, leukotrienes).

Reference:
Robbins and Cortran: Pathologic Basis of Disease, 9e

Other sources:
Wikipedia page


What is membrane-partitioning free energy? Can it be simulated? Firstly, is there a strict definition of the "membrane-partitioning free energy"? It is banded around in membrane biology, but I have never seen it strictly defined. The only non-scholarly site that google shows is this Q&A on quora, and the answer there even has ambiguity in what is defined as partitioning in the membrane. This seems wholly unclear.

Furthermore, is it possible to study free energy changes upon partitioning in GROMACS, or with any other molecular dynamics simulations? If not, what are the methods I would need to use to determine the free energy of partitioning?

Links and citations for further reading on this topic are encouraged.

In the biological context, membrane-partitioning is usually referring to the stage in which the transmembrane-destined region of a protein moves from interacting with the water, to interact with the interface of the membrane.

In the diagram below showing a four step thermodynamic cycle, the partitioning free energy can be referred to as-is ΔGwiu in terms of free energy where w is water, i is the interface, and u is unfolded. The image comes from the same paper that introduced the famous Wimley and White octanol-interface scale from 1999.

Note that in a more recent 2015 article, they comment that the partitioning phase ΔGwiu is generally the only experimentally accessible step. With that in mind, simulating ΔGwif where f is the folded helix becomes necessary. This 2014 Nature Comms paper use folding-partitioning molecular dynamics simulations to estimate the free energies that are experimentally inaccessible. They used Gomacs 4.5. In fact, a study using a simulation from 2005 suggests that folding isn't necessarily required for insertion of the helices.

Note that all the information here is behind a paywall. Feel free to ask me for clarification or expansion in the comments.


What beetle is this? I've found it in my kitchen. It seems to be that he flew through the window from the street.

The country is Russia.

This is Mealworm beetle, Tenebrio molitor, a species of darkling beetle.

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

Thank you @terdon for help!


What's the evidence against SARS-CoV-2 being engineered by humans? A couple of colleagues suggested in a discussion that the virus that causes COVID-19 appears to be made by humans, since nature could not have produced such an efficient virus — that spreads so fast and whose patients are contagious quite some time before showing signs of infection.

Since my knowledge of biology is very limited, my only counterargument for such a conspiracy theory was along the following lines:

there is a consensus that the most probable source of the first infection was in an animal market in China.
since that animal market was actually composed of a plethora of animals belonging to various species (mixed with humans), a virus had a bigger chance of evolving a mutation that might infect an individual from another species (a thing that is way less unlikely in the wild since many of those animals do not sit close to each others or next to humans).

Clearly, I have made a little story that might be quite far away from how SARS-CoV-2 infected humans, so I am interested in a scientific arguments to support my cause.

Question: What are the main scientific arguments that can be used to debunk COVID-19 being engineered by humans?

Answers that also include explanations more accessible to laymen are greatly welcomed.

At the moment, there is very little scientific literature about this, but I found two papers that address the problem and are fairly easy to understand. You can find them in the references. Reference 1 is probably the most interesting and is the basis for this answer.
Edit: It is also interesting to read reference 2 on the origin of SARS-CoV-2; the article also addresses some of the conspiracy theories.
As far as I can see, there are a few major points taken up by conspiracy theories.
1. SARS-CoV-2 leaked from a lab in which research on the Bat CoV (RaTG13) was done:
Unlikely, since the viruses share only around 96% sequence homology, which translates into more than 1100 sites where the sequence of SARS-CoV-2 viruses is different from RaTG13. The mutations are distributed throughout the viral genome in a natural evolutionary pattern, making it highly unlikely that SARS-CoV-2 is a direct descendant from RaTG13. For comparison, the original SARS-CoV and the intermediate host palm civet SARS-like CoV from which it originated shared 99.8% sequence homology, showing a much closer relation.
2. The S (spike) protein from bat SARS-CoV cannot be used to enter human cells via the human ACE2 receptor and therefore has been adapted in the lab:
This is untrue, since a 2013 study of a novel bat coronavirus was published showing the ability of the virus to enter cells via the ACE2 receptor. See reference 3 for details.
3. The spike protein of SARS-CoV contains a unique inserted sequence (1378 bp) located in the middle of its spike glycoprotein gene that had no match in other coronaviruses:
As shown in reference 4, the sequence comparison of the SARS-CoV-2 with closely related other coronaviruses shows that this sequence is not unique to the new virus but is already present in older strains. It shows some difference due to inserted mutations.
4. The claim that SARS-CoV-2 contains four insertions from HIV-1:
The paper claiming this has now been retracted due to severe criticism, and additionally a renowned HIV expert published an analysis (reference 5) demonstrating that the HIV-1 claimed insertions are random rather than targeted.
5. The claim that the SARS-CoV-2 virus is completely man-made:
To design such a "weapon grade" virus in the lab, the design would usually start from a known virus backbone and then introduce logical changes (for example, complete genes from other viruses). This cannot be seen in the genome of the virus; rather, you see randomly distributed changes throughout the genome coming from virus evolution and not directed cloning. It is more likely that this virus originates from the recombination of a bat CoV (to which it is closely, but not directly related) and another, not yet known CoV in an intermediate host, like the palm civet for the 2003 CoV.
References:

No credible evidence supporting claims of the laboratory engineering
of SARS-CoV-2
The proximal origin of SARS-CoV-2
Isolation and characterization of a bat SARS-like coronavirus that
uses the ACE2 receptor
Is SARS-CoV-2 originated from laboratory? A rebuttal to the claim of
formation via laboratory recombination
HIV-1 did not contribute to the 2019-nCoV genome