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

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

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

I think perhaps a picture might help, also see some lecture notes here, where I pulled the pictures from: in short, if you have an unbroken chain, you can't stick it through a hole except as a loop unless you start at the very end, and often you don't want to do that.

Signal sequences can be anywhere on the protein. That portion is the part of the peptide that binds to the translocator pore in the membrane. That portion has to stay bound for the process to continue: it isn't possible to just "feed through" the growing polypeptide without securing it somehow, and that's precisely what the signal sequence is doing by interacting with the translocon.

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

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

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


Are humans not sexual dimorphic? Can genetic XY but SRY not expressed become pregnant? My understanding was that XX/XY was how sex is determined in mammals, and so humans as well.

A science teacher posted this regarding transphobia:

  "I just commented this on a transphobic post that was all like, "In a sexual species, females have two X chromosomes and males have an X and a Y, I'm not a bigot it's just science." I'm a science teacher so I responded with this.
  First of all, in a sexual species, you can have females be XX and males be X (insects), you can have females be ZW and males be ZZ (birds), you can have females be females because they developed in a warm environment and males be males because they developed in a cool environment (reptiles), you can have females be females because they lost a penis sword fighting contest (some flatworms), you can have males be males because they were born female, but changed sexes because the only male in their group died (parrotfish and clownfish), you can have males look and act like females because they are trying to get close enough to actual females to mate with them (cuttlefish, bluegills, others), or you can be one of thousands of sexes (slime mold, some mushrooms.) Oh, did you mean humans? Oh ok then. You can be male because you were born female, but you have 5-alphareductase deficiency and so you grew a penis at age 12. You can be female because you have an X and a Y chromosome but you are insensitive to androgens, and so you have a female body. You can be female because you have an X and a Y chromosome but your Y is missing the SRY gene, and so you have a female body. You can be male because you have two X chromosomes, but one of your X's HAS an SRY gene, and so you have a male body. You can be male because you have two X chromosomes- but also a Y. You can be female because you have only one X chromosome at all. And you can be male because you have two X chromosomes, but your heart and brain are male. And vice - effing - versa. Don't use science to justify your bigotry. The world is way too weird for that shit."

If you're asking if humans are a sexually dimorphic species, the answer is "yes".
If you're asking based on the viral response of the science teacher, then the answer is still, "yes".  What is described above are chromosomal abnormalities, or other disorders of development, but they are still describing sexual dimorphism in the phenotype. However, the answer itself is incomplete, as it's written out of political motivation.
Whilst true that a person can present, phenotypically, the opposite of their genetic sex, this isn't akin to them "being male/female" counter to their allosomes.  Of course, this in itself can prove to be a contentious issue - how is sex defined?  Under normal circumstances, phenotype is the obvious way of knowing. If someone has the external genitalia of a male, they can be assumed to be male, and vice-versa for females.  When it comes to chromosomal abnormalities, there is an "error" in devlopment, where the genotype is not properly expressed in the phenotype, and so while presenting as one sex, the "true" sex as determined by the genotype is the opposite.  It should also be noted that sexual characteristics can be ambiguous certain cases, creating abnormal sexual presentation, such as in hermaphroditism/pseudohermaphroditism, or "intersex" (the quote mentions 5-alpha-reductase deficiency, which is associated with male pseudohermaphroditism).

The problem with the quote above (at least in the way it is written) is it appears to suggest that chromosomes have little to do with phenotype, as in sex determination, and that this carries over to gender dysmorphic patients.  These are both mostly false.  Gender dysmorphic patients generally do not have any allosome abnormalities, and the reason that the given examples are deemed "errors" (eg XX male syndrome; 47,XXY) is because that is what they are, as well as being rare.  The typical effect of these problems is that the patient is infertile, (i.e. they are not sexually functioning, and have reduced biological fitness).

In short, the teacher is correct in the examples used, but overstating them with regard to the general population, and with regard to transphobia and gender dysphoria.  Humans are indeed sexually dimorphic but as with any complex biological system, errors expressing genotype can occur.


List of proteins by number of amino acids / chain length Is there any protein database online where I could obtain a list of proteins ordered by the length of their chains / number of amino acids, starting from the shortest, as well as to see their amino acid sequences?

I'd like to start from the short & simple protein structures to see how their particular sequences of amino acids translate into their folding shape, and what those short chains are capable of doing in organisms. (I heard about the LILs, but they are artificially-generated and consist of just two amino acids, Lysine and Isoleucine, so not much variety to study in there :q )

But I'm quite new to these databases, they present a lot of details, but usually not the one I'm looking for, and one has to know what too look for first to get any meaningful information :q

You can find the data you need in the Protein Data Bank.

  Since 1971, the Protein Data Bank archive (PDB) has served as the
  single repository of information about the 3D structures of proteins,
  nucleic acids, and complex assemblies.

  The Worldwide PDB (wwPDB) organization manages the PDB archive and
  ensures that the PDB is freely and publicly available to the global
  community.

Each of the PDB member organisations provides the same data with a different interface:

PDBe,
PDBj,
RCSB.

In general, you either query the database through one of the web interfaces, or you download all the data and search it locally. In this case, the RCSB website has the option you asked about (sorting by the residue count):

Alternatively, you could download:
ftp://ftp.wwpdb.org/pub/pdb/derived_data/pdb_seqres.txt
and parse it and sort it as you wish.
This file has sequences of all chains in the PDB entries.

But since your goal is to find the relationship between the sequence and the folded structure, you should probably start from reading about the protein folding problem and about methods used in protein structure prediction.


Why does regular exercise increase brain volume? It has been shown in several studies that regular aerobic exercise increases brain volume in aging humans. The changes were observed in hippocampus and were correlated with dramatic reduction of age-related dementia. Interestingly, the intensity of training had little influence on the results: walking, climbing stairs, gardening were just as effective at reducing dementia as more strenuous exercise.

What is the biological mechanism behind this phenomena?

Fig. The aerobic exercise group showed an increase in the anterior hippocampus and no change in the posterior hippocampus.[1]

Erickson et al. Exercise training increases size of hippocampus and improves memory. PNAS. 2011.
Colcombe et al. Aerobic exercise training increases brain volume in aging humans. J Gerontology. 2006
Ravaglia, et al. Physical activity and dementia risk in the elderly. Neurology. 2008

Well, Erickson et al (2011) attribute the increase in brain volume in the aerobic exercise group to brain-derived neurotrophic factor (BDNF).

Specifically (p. 3020):

  In fact, we found here that changes in serum BDNF levels were
  associated with changes in anterior hippocampal volume; an important
  link because the hippocampus is rich in BDNF, and BDNF levels increase
  with exercise treatments in both rodents and humans. BDNF is a
  putative mediator of neurogenesis and contributes to dendritic
  expansion and is also critical in memory formation. Our results suggest that
  cell proliferation or increased dendritic branching might explain increased
  hippocampal volume and improvements in memory after exercise

with the caveat:

  however, increased vascularization (15, 16, 33) and dendritic
  complexity (34) may also be contributing to increased volume


What is the name of the property of viruses can activate a second time, with different symptoms? The Varicella zoster virus causes chickenpox in children and shingles in adults.

It appears after the initial infection, it can go dormant in the nerve, and reactivate itself decades later.

In chickenpox - the symptoms are:

  characteristic skin rash that forms small, itchy blisters, which eventually scab over. It usually starts on the chest, back, and face then spreads to the rest of the body

In shingles - the symptoms are:

  a painful skin rash with blisters involving a limited area. Typically the rash occurs on either the left or right of the body or face in a single stripe.

My question is: What is the name of the property of viruses can activate a second time, with different symptoms?

Viral latency is the best term to use for viruses that can lie dormant.

I have not come across a specific term for latent viruses that recur with different symptoms. This is probably because "different" is very subjective. Many pathogens can cause several different forms of disease depending on factors such as the route of exposure (i.e. where and how the pathogen got to its destination). Obviously the latent infection has a different pathophysiology to chickenpox. Due to its latency in dorsal root ganglia, shingles typically results in a localised rash, but there are less common disseminated forms of shingles that can look very similar to chickenpox.


What is the relationship between sexual and natural selection? In Evolutionary ecology: Novelty makes the heart grow fonder, they say:

  Thus, it seems that the diverse coloration in this species is promoted by both natural and sexual selection.

I had always thought of sexual selection as a subset of natural selection. What's the right way to think about the relationship between the two?

You're not wrong, per se, but in practice they refer to two different concepts.  I honestly think the Wikipedia article does a good job, in particular this sentence:

  In summary, while natural selection results from the struggle to survive, sexual selection emerges from the struggle to reproduce.

It also cites Darwin:

  The sexual struggle is of two kinds; in the one it is between individuals of the same sex, generally the males, in order to drive away or kill their rivals, the females remaining passive; whilst in the other, the struggle is likewise between the individuals of the same sex, in order to excite or charm those of the opposite sex, generally the females, which no longer remain passive, but select the more agreeable partners.

The whole argument is moot when dealing with individuals that aren't reproducing sexually, of course.


Can people with AIDS/HIV be vaccinated? If there is no immune system,it  seems like vaccines wouldn't do much since there is no adaptive immune system to develop antibodies and memory cells. But can people with AIDS/HIV still be vaccinated? It is expected that a normal person will have antibodies to attack the minimal infection produced by the vaccine and generate memory cells, but without an immune system I expect vaccines to be deadly.

Is that right?

Can people with AIDS/HIV be vaccinated?

Yes. Immunization is an important part of the overall treatment strategy for HIV positive individuals. HIV infection is a risk factor for a number of vaccine preventable infectious diseases. Immunization in these patients is particularly important because of their increased risk of developing disease. (See Cecil Medicine Ch 396)
Can the immune system still mount a response to the vaccine?
Yes. HIV infection does lead to a decreased immune response. Though the primary deficiency is a decrease in both CD4+ (helper) T-cell count and function, there is, perhaps consequently, B-cell dysfunction as well. This would suggest that vaccines are less immunogenic. When this is studied directly, as would be expected, we see that vaccines are less immunogenic, but they are still effective.
Which vaccines are given?
Specific recommendations are based on both the age of the individual and their immune status. As a rule, vaccines are more effective when given early in the natural history of an HIV infection or after immune reconstitution with HAART, but there is some effectiveness and little risk of heat killed or subunit only vaccines even in highly immunosuppressed individuals. While live attenuated vaccines are contraindicated in individuals with a CD4+ cell count below 200, these vaccines are given routinely to other HIV positive patients. Current guidelines are found here. Here is the main figure from those guidelines:


Can Biologists identify all viruses? I went to the doctor today with my girlfriend, and the doctor said that she had a virus but doesn't know which one and she should let the infection heal with some rest.

The fact that the doctor didn't know what type of virus she has bothers me.

Do physicians/biologists not know all the different types of viruses out there? Is it not possible to identify all of them?

Do physicians/biologists not know all the different types of viruses out there?

No, Biologists don't know all the viruses that exist out there. There's a lot! We do know many of the ones infecting humans, though, especially the ones leading to the most common diseases.

  The fact that the doctor didn't know what type of virus she has bothers me.

Without knowing any symptoms, your girlfriend likely had was some kind of influenza (flu), rhinovirus (cold), norovirus (diarrhea, etc) or respiratory syncytial virus (strong). That's just the most common virus infections. Identifying those is possible (see lab tests for norovirus or influenza), but it's unnecessary in most cases.

The thing is, no matter which of these she has, the medical advice will stay the same - rest and fluids. So identifying them is just going to add time and money.

There are some cases where viral identification is done even for these diseases. For example, before giving an antiviral like Tamiflu, which is for example given to pregnant women with the flu. Before giving an antiviral, it should be established that she is indeed infected with the influenza virus. These tests are also done in patients who are hospitalized. In some countries and years, all influenza cases are screened to later know what strains of the virus infected how many people and how it spread.

As an example, if the result of the test doesn't change the treatment, the influenza test is recommended against by the CDC. With a gastrointestinal issue where norovirus is suspected, nobody is going to make an identification for a straightforward case.


How to measure metabolic rates of microscopically small animals? I want to measure metabolism rates in Tardigrades

Metabolic rates will be assessed immediately following their exit from cryptobiosis (an animal dormant state).

I know that oxygen levels is the usual way to measure metabolism, but tardigrades are extremely small and hence oxygen level differences will be minute. Is there any other way to characterize metabolic rates, or is there a way to make the oxygen method viable?

Metabolism in other small organisms, such as bacteria, are measured by taking the metabolism of a very large population of organisms, and then dividing that by the count of organisms in order to obtain the metabolic rate of a given individual.

In this paper on the metabolism of E. coli, they looked at the various input and output chemicals. Glucose, biomass, oxygen, and carbon dioxide were all observed. Observation of multiple variables also helps in the reduction of errors by using the stoichiometric balance to make sure that no errors have occurred in the measurements.

The methodology section of the paper had the following techniques:

  Continuous cultivations were performed at 28 °C, at a stirring speed
  of 800 r.p.m., and the pH was controlled at pH 6·6 with 2·5 mol NaOH
  l−1. The 2-l bioreactor (model SGI 7F-Set2; Setric) was equipped with
  standard measuring and control units (temperature, pH, dissolved
  oxygen, stirrer speed). A constant aeration rate of 1·33 v.v.m. was
  achieved by a mass flow controller (Brooks). Continuous cultivation
  was performed for at least eight residence times at a given dilution
  rate; steady-state conditions were verified by constant optical
  density and oxygen and carbon dioxide transfer rates. Except for
  glucose, all other substrates were in excess. The concentration of
  dissolved oxygen was always maintained above 20 % of air saturation.
  Analytical techniques.

  Culture liquid was withdrawn from the bioreactor into an ice-cooled
  beaker. Cell dry mass was determined gravimetrically after
  centrifugation of a known sample volume. The pellet was washed twice
  with 0·9 % w/v NaCl and dried at 40 °C under vacuum for 48 h.
  Elemental biomass composition was analysed with a PE 2400 II elemental
  analyser (Perkin Elmer). Glucose was measured enzymically by a YSI
  glucose analyser (model 2700; Yellow Springs Instrument Co.). Organic
  acids, i.e. acetic acid, formic acid, lactic acid and pyruvic acid,
  were analysed by HPLC using an HPX-87H Aminex ion-exclusion column
  (Bio-Rad). The column, connected to a UV detector (λ=210 nm) and RI
  detector, was eluted at 50 °C with 5 mmol H2SO4 l−1 at a flow rate of
  0·5 ml min−1.

If the tardigrades are grown in solution, an identical methodology can be used to measure respiration rate.


Why is it said that bacteria have no membrane-bound organelles, when they often have one or more flagella? Why is it said that bacteria have no membrane-bound organelles, when they often have one or more flagella?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386205/  "Cilia and flagella .. are membrane-bounded organelles with unique membrane,"

Also, there is a biological motor (I don't know whether it's considered part of a flagellum or considered to be outside the flagellum, driving it?), but the motor surely has parts, e.g. a flagellum motor -like some mechanical motors, has a part, a "stator".  And surely these parts have membranes.

I understand there's one bacterium discovered, that does have a membrane-bound organelle mentioned here "There is at least one species of bacteria that has a clearly membrane-bound structure inside it called an acidocalcisome (I think that's how it's spelled). This organelle was.. discovered.. this is obviously a minor (albeit important for that bacterium) exception to the rule...that prokaryotes lack membrane-bound organelles."

Note- Alcamo's Fundamentals of Microbiology: Body Systems p124  this link from google books mentions other cases of membrane-bound organelles in bacteria including a discover as early as 1994. here

But putting aside the bacteria that have been discovered to contain membrane-bound organelles and going back to before those discoveries.. The texts that describe bacteria as having a flagellum, say that they don't have membrane-bound organelles. Why is this?

I suppose an answer might be that when people say that a bacterium contains no membrane-bound organelles, they mean except for any flagellum that it has.  They're referring to the main body of the bacterium, like one might refer to the torso of a human.

Prokaryotic flagellum is very different from eukaryotic flagellum: it's not surrounded by a biomembrane (as in eukaryotes) and its composition is distinct. Actually, they only have in common the name and the function:

  The term flagella is ambiguous. It refers to bacterial structures composed of flagellin protein and to eukaryotic structures composed of microtubule proteins.

Source: https://www.ncbi.nlm.nih.gov/pubmed/7378551

It's clear that prokaryotic flagellum is just a protein-made structure that crosses the membrane and grows outside it, as represented in this image (notice the TEM at the bottom right):


How are Raunkiær's plant life forms viewed today? At the beginning of the 20th century, Raunkiær proposed a typology of plant life-forms based on where they bear their buds, roughly as:

cryptophytes: belowground

hemicryptophytes: at the surface

chamaephytes: close to the surface

phanerophytes: projected above the surface

Are these still held to be useful / biologically meaningful categories? Is there a different typology preferred (eg. tree/shrub/subshrub)? Or are people moving toward gradients of quantified traits instead of typologies (eg. measuring plant height, specific leaf area, etc.)?

Oreotrephes, it all depends on the needs. Reproductive schemas don't exclude shape schemas. There has been, however, a shift to cladistics in classification, which means to give scientific names ONLY to monophyletic groups, i.e. groups that include all the descendants of a single ancestor - and only its descendants. But we still use tree/shrub distinction and epiphytes, for instance, but that's to describe the ecology of species, helping identify them, not to classify them on these grounds alone.


How to determine which is the nucleotide sequence of a gene? I have came across a few  genes that show different nucleotide sequence in different databases. I then found out that the sequences are actually reverse complement of each other. How do i determine which is the actual nucleotide sequence of a gene,and not the reverse complement version of it?

You run a blast of your sequence. Then explore the results and you'll see somewhere that says "strand"  and is indication whether is plus/minus.

https://blast.ncbi.nlm.nih.gov/Blast.cgi

Also blast has a graphical interface in which you'll clearly see the matching and non-matching bases. Therefore it should help you to identify the differences between the 2 sequences.


What is "bacto" peptone? Standard recipes for yeast medium often include "bacto-peptone". Is this the same as bacteriological peptone? Is there an authoritative source that spells it out?

See here. Bacto is a brand which used to be marketed by Difco. It is a casein (milk protein) hydrolysate.


Publicly available resources for learning metagenomics We are starting a metagenomics project in our research group to study microbiota in the respiratory tract. Since the are no books yet about metagenomics, seems reading some reviews and online tutorials is the only alternative.

Could you suggest me essential papers, websites or other resources useful for my purpose.

Thanks

The Coursera Bioinformatic Methods courses include classes on metagenomics and, more importantly, tools to use when applying these methods. I have not taken this particular course, but Coursera is generally very good with getting hands-on experience using computational tools. A course-like setting may also be conducive to group learning.


How to know what the expected value is? I am confused as to how I was meant to know E for a X^2 test in the following question:

2.i and 2.ii give no more information.

Not knowing what to do I used E as 0 for the first row and 40 (3+37) for the second row, but that was just a guess. It was wrong and the correct answer for E is 20.

I suspect this has something to do with the 20 fields but I can't beleive that I'm just meant to know they expect one butterfly per field...

How was I meant to know E?

The expected value is what the values would be if the tested conditions had no effect on the sample distribution. In your case, you are testing the effect of herbicides on butterfly populations. If the presence of herbicides wouldn't matter you would expect an equal number of butterflies on fields with herbicides as without.

So, the total number of butterflies being $37 + 3 = 40$, you would expect $\frac{40}{2} = 20$ butterflies on fields without and $\frac{40}{2} = 20$ on fields with herbicides.


How does a fertilized egg form 23 pairs of chromosomes? I am always confused about this...so when one cell which has 23 pairs of chromosomes undergoes the two meiotic divisions it produces four cells containing 1 chromatid of every chromosome pair so when this fertilizes the opposite gamete (of course it has also one chromatid of each chromosome pair) when they are fertilized they make one 23 chromosomes because 23 chromatid from one and 23 from other and they will form 23 chromosomes not 23 pairs of it, so my question is how they form 23 pair of it or to make it homologue..please clarify with some pics??...tnx

After fertilisation the zygote has two copies of each of the chromosomes (not worrying about sex chromosomes). When each of these is replicated the cells will have chromosome pairs, which will then divide in mitosis.

The classical chromosome image of pairs of X-shaped chromosomes relates to the situation at mitotic metaphase when each of the chromosomes has replicated and consists of two sister chromatids. As anaphase proceeds the splitting of the centromeres means that each of the sister chromatids becomes a chromosome, and each cell ends up with a pair of each chromosome type, just like a zygote.


Are there enzymes for every given reaction? This is a question that's been bugging me, and I haven't been able to find a definite answer anywhere.

We know there are thousands of enzymes (proteins, let's ignore catalytic RNA for now) that catalyze many different reactions, and they do this because they have the correct shape to fit the substrates.

Theoretically, given some reaction, can an enzyme be created to catalyze that reaction? Or is there some reaction that it's not possible to catalyze with an enzyme? Can any given shape be created out of polypeptide chains? If not, what determines the shapes that it's possible to create?

This will probably be a difficult question to answer definitively without some hand-waving or redefining the question; I can't imagine proving the negative result that no enzyme is possible for a given reaction, except for some cases where the reaction is just thermodynamically impossible outside of incredible conditions (for an extreme example, what about hydrogen fusion: the reaction exists, but the conditions necessary are outside the tolerance of protein-based catalysts).

As @tomd pointed out in a comment, enzymes do not change equilibrium, so enzymes are only possible for reactions that are thermodynamically favorable. However, some enzymes couple reactions that are thermodynamically unfavorable with highly favorable reactions to produce a net thermodynamically favorable reaction, which greatly increases the number of reactions that can theoretically be catalyzed.

As for whether any shape can be created out of polypeptides: given the diversity of amino acids and the structural effects of the tertiary structure of proteins, there is a near limitless array of combinations which exceeds human comprehension, but not a truly mathematically infinite number. There are interesting projects such as this one that seek to harnessed underutilized computing power to iterate all of these possibilities to search for useful drugs and explain the causes of disease.


I'm trying to identify a tree i saw in Taormina, Sicily, Italy. Can anyone help? What is the identity of this tree? These pictures were taken in Taormina, Sicily.

It looks like the Silky oak, Grevillea robusta, which is btw not related to our indigenous oaks (quercus).
It's native only to eastern Australia, so planted in Sicily.
https://pommepal.wordpress.com/tag/silky-oak/


Do human cells contain only one copy of the genome? Does each cell contain only a single copy of its genome? Or are there ever 'extra' copies present.

Reason behind question: Wondering whether gene mutations could be corrected by referencing a 'backup copy'.. If such a thing exists..

As a quick answer, yes, most human cells carry 2 copies of the genome and are known as diploid cells. One copy comes from each of your parents, so they aren't identical, but usually pretty close. Sperm and egg cells only carry one copy of the genome and are known as haploid. During fertilization the 2 cells merge their copies and make a diploid zygote. At the chromosomal level, humans have 23 chromosomes, so a diploid cell has 2 copies of each so a total of 46.

As far as repairing damaged DNA, using one chromosome to repair its damaged counterpart is known as Homologous Recombination.


If bacterial resistance randomly occur, then why limit broad-spectrum antibiotic use? If there is importance to study some discipline, then one of the main matters is its applications, so besides the primary goal of knowing the truth of the matter regarding what that discipline is investigating, applicability or usefulness of that study in other fields or in the field itself is a very important matter. I'll direct my attention here to Evolution, and its mechanisms. So accordingly if something that I personally want to come up with is application of that knowledge to the field of my work.

In reality we don't study evolution extensively at college level in medicine, since it doesn't have a direct clinical impact on the diagnosis and treatment of patients in most of the cases. However, one possible area of interaction is "bacterial resistance to antibiotics", since this is related to "mutations", and generally viewed as a mechanism whereby the bacterium adapts to its environment.

Now all of my life in medicine from college through specialty and academic teaching, we've never ceased being reminded about not dispensing antibiotics liberally, and the main concern outlined is "emergence of resistant strains of bacteria" due to this liberal use of antibiotics itself. There are other reasons of course, like side effects and cost, but they are not the main concern most of the times.

During my recent review of Evolution, looking at the introductory courses that were cited to me by many participants here, in particular this page of Evo101 titled "Mutations are Random" I was really shocked to know that even the mutations that resulted in bacterial resistance were not "directed mutations", i.e. it is not the case that the exposure to the antibiotic caused the bacteria to have that mutation in the first place, actually the page mentions Esther and Joshua Lederberg experiments showing that those resistant bacteria were already there before the population was exposed to the antibiotics?

So why have we been always reminded by bacteriologists of limiting our antibiotic usage if emergence of drug resistance is not due to exposure to it?

Actually, its not only that, many lectures we attend, which are pretty much delivered by official bodies, does mention of emergence of antibiotic resistance as a DIRECTED mutation response to exposure to the particular antibiotic, that almost most of us we clinicians became to think that this is a fact. For example hospital bacteria are of the most resistant ones, especially those in intensive care facilities. The association between exposure to antibiotics and emergence of drug resistant bacteria to them is almost hammered in our brains, that to discover that the mutation was already there before exposure to the antibiotic seems quite shocking, at least to me in person.

My question here is the following:

  Is it a scientific fact that emergence of bacterial resistance through mutations is always random, i.e. in the sense that it is not a directed response to exposure of the population to that antibiotic?

For instance this seems to be a counter-example.

If that is the case then why bother about liberal use of broad-spectrum antibiotics? I mean as far as emergence of bacterial resistance is concerned!

I mean its not the case that I'm going to eradicate the "useful bacterial" that could rival the pathogenic resistant bacteria, by that liberal use of broad-spectrum antibiotics. If that happens temporarily we can in principle replace them back, like with the use of probiotics.

During my surfing of the web I found that page addressing the same point, but the responses are not that explicit, and far from being convincing?

You're correct, this is extremely relevant, and it's unfortunate that your medical education didn't include good instruction about evolution.

You point to some very useful and interesting studies. I'm particularly fond of the studies that demonstrate the early existence of antibacterial resistance genes, e.g., in ancient permafrost.

Now to your question

  Is it a scientific fact that emergence of bacterial resistance through mutations is always random, i.e. in the sense that it is not a directed response to exposure of the population to that antibiotic?

I think the issue here is a conflation of two separate concepts. Mutation is one mechanism for producing variation. Mutation can be understood as a stochastic process, causing changes in the genome of an individual by chance.

Evolution occurs because of existing variation. Evolution is not a stochastic process. It is a biased process, a change in the distribution of existing variation.

The emergence of antibacterial resistance is evolution that results from selection acting on existing variation. Emergence here refers to emergence of a resistant variant within a population. Selective pressure (application of antibiotics) causes a predictable change in the frequency of genes that would allow reproduction in that environment, the frequency of existing resistance genes increases in the bacterial population.

Though there is evidence for important antibacterial resistance mutations pre-dating the use of antibiotics, this does not rule out the occurrence of spontaneous mutations, as demonstrated in the article you linked. The production of genetic variation by random mutation can be followed by a rapid increase in the frequency of a new genetic variation that is selected for in a given environment. This can be particularly likely in organisms with high error rates, short generation times, and large numbers of individuals. The spontaneous mutation isn't directed, as you say. It is random. The selection of that particular random mutation is directed, though.  Once the random mutation occured, then we can say the variation exists. Then selective pressure acts on existing variation, allowing evolution, a change in the frequency of the, in this case, gene for resistance.

Goodman & Gilman, one of my go to pharmacology references, actually has an excellent discussion of these concepts as they relate to antibacterial resistance, in Ch. 48, under the subsection EMERGENCE. There is a good discussion of the various mechanisms of emergence, but this general statement is helpful:

  Mutations are not caused by drug exposure per se. They are random events that confer a survival advantage when drug is present. Any large population of drug susceptible bacteria is likely to contain rare mutants that are only slightly less susceptible than the parent. However, suboptimal dosing strategies lead to selective kill of the more susceptible population, which leaves the resistant isolates to flourish.


Will a bone marrow transplant change one's blood type? Will a bone marrow transplant change one's blood type?

Or is the donor blood type matched with the person before transplant?

Bone Marrow transplants are extensively matched in order to prevent rejection. Current matching methodology is HLA matching: Stanford Children's Hospital Guidelines

  How are a donor and recipient matched?
  Matching involves typing human leukocyte antigen (HLA) tissue. The antigens on the surface of these special white blood cells determine the genetic make-up of a person's immune system. There are at least 100 HLA antigens; however, it is believed that there are a few major antigens that determine whether a donor and recipient match. The others are considered minor and their effect on a successful transplant is not as well defined.

  Medical research is still investigating the role all antigens play in the process of a bone marrow transplant. The more antigens that match, the better the engraftment of donated marrow. Engraftment of the stem cells occurs when the donated cells make their way to the marrow and begin reproducing new blood cells.

However, because the HLA matching doesn't utilize blood-type and the recipient's marrow is destroyed in the process, then if the donor's marrow produces different red blood cells - then so will the recipient with time:

  Does my blood type change after SCT or [Bone Marrow Transplant]?

  Yes.  The recipients blood type eventually changes to the donor type.  That means if you had a blood type of A+ prior to transplant and your donor had a blood type of O, eventually your blood type would become O.  I may take several weeks, possibly months for your original blood type to disappear, but eventually it will.

What's interesting is that blood-typing is not be expressly necessary with the modern bone marrow transplant process. The danger of mixing two antagonistic blood types in vivo is that the recipient's immune system attacks the foreign red blood cells resulting in body-wide rejection. However, because the immune system's response capabilities are decimated by the destruction of the recipient's bone marrow (usually accomplished via chemotherapy or radiation), it can't mount much of an attack in the first place. That's not to say the body can't mount an attack, or that the donor's tissue can't mount an attack on the recipient (Graft-Versus-Host-Disease [GVHD]) - but the better the HLA match the less likely issues are to arise, which is why we do the more accurate and relevant HLA matching instead of blood-typing.


How are isovolumetric contraction and afterload related in the cardiac cycle? In the cardiac cycle isovolumetric contraction occurs and causes a pressure gradient. The "afterload" is the pressure exerted on the ventricle from the artery.

Is the afterload the cause of isovolumetric contraction, or what is the exact relationship between them?

The important thing to remember is that the "afterload" on the heart is the diastolic blood pressure in the aorta. In other words, the pressure in the aorta that the heart must overcome to open the aortic valve and create a pressure gradient to force blood into the aorta and generate flow. The isovolumetric part of the contraction is the generation of pressure up to the afterload 'pressure'. Once the pressure in the heart is higher than the pressure in the aorta a pressure gradient is generated and the aortic valves open and blood flows out of the heart into the aorta. During this movement of blood the heart is contracting again and changing volume (i.e. not isovolumetric anymore).

If the afterload is higher (i.e. higher blood pressure or hypertension) it increases the work on the heart because it has to generate an even higher pressure within the heart to open the aortic valve to generate the pressure gradient and flow.

If the afterload is lower (i.e. low blood pressure or hypotension) the work on the heart (with all other factors remaining constant) would decrease because the pressure to open the aortic valves and create flow is lower. The diagram below is available online at this link. This is a very common picture/diagram that can be found in any cardiovascular physiology textbook.

Note: In the picture below the isovolumetric contraction is only the time between the two vertical lines as indicated. During that isovolumetric contraction you can see that the volume (i.e. the red line) stays the SAME, but the pressure in the ventricle significantly increases up to the point of aortic pressure.


Are humans Gnathostomates? Gnathostomates are vertebrates having jaws. But when I search on the internet for Gnathostomates, I always find out that they are sharks and fish-like organisms.

But are humans not also Gnathostomates? Don't we have jaws?

Absolutely, humans belong to the superclass Gnathostomata. It's simply the class of jawed vertebrates, and includes 99% of vertebrates.  It also includes the class Mammalia, which includes humans.

For basic and fairly light reading, check out Wikipedia on Gnathostomata and Mammalia.


Do birds ever fly in clouds? Do (some) birds ever fly in fog or clouds so that they would not be able to see either the ground or the sun? Assuming the visibility is good enough so they can see obstacles in time to avoid them.

If they do, how do they maintain straight flight?

Inner ear is inadequate in the air, because it can only sense the sum of gravity and acceleration, which is just the (reaction to) aerodynamic forces and those are always orthogonal to the wings. To an extent, it can also detect rotation, but this is not good enough to keep precision for minutes and hours in cloud. So how do birds know where is up?

Yes, they do.

Pilots normally say that "birds are day VFR only", you're gonna read this a lot on the internet. VFR means Visual Flight Rules, where the pilot operates the aircraft in weather conditions clear enough to allow the pilot to see where the aircraft is going. Thus, they are implying that birds avoid flying at night and inside clouds.

However, this is wrong. Birds do fly inside clouds (and at night), especially migratory birds that have to fly non-stop for weeks or months. They cannot avoid flying at night (of course) and, in several situations, they cannot avoid flying towards a cloud.

According this paper in Science, from Weimerskirch et al. (2016), frigatebirds can even do this on purpose!

  We studied the three-dimensional movements and energetics of great frigate birds (Fregata minor) and showed that they can stay aloft for months during transoceanic flights. To do this, birds track the edge of the doldrums to take advantage of favorable winds and strong convection. Locally, they use a roller-coaster flight, relying on thermals and wind to soar within a 50- to 600-meter altitude band under cumulus clouds and then glide over kilometers at low energy costs. To deal with the local scarcity of clouds and gain longer gliding distances, birds regularly soar inside cumulus clouds to use their strong updraft, and they can reach altitudes of 4000 meters, where freezing conditions occur. (emphasis mine)

Source: Weimerskirch, H., Bishop, C., Jeanniard-du-Dot, T., Prudor, A. and Sachs, G. (2016). Frigate birds track atmospheric conditions over months-long transoceanic flights. Science, 353(6294), pp.74-78.

PS: You have two questions here, specially after your edit. I suggest that you post another question regarding the spatial orientation, since asking different questions (even if they are related) in the same post is not nice, and it's a reason to close ("Too broad: Avoid asking multiple distinct questions at once"). However, it's worth mentioning that apparently birds do suffer from spatial disorientation when there is no visual cue. According to this relatively old paper, "Spatial Disorientation in Birds":

  The only conclusion is that birds are susceptible and suffer from spatial disorientation, and further that the causes of spatial disorientation in birds are exactly the same as those which affect the human pilot, namely; (a) the loss of true visual cues to the horizontal; (b) inexperience in flying under such conditions where visual cues are lost;


Why are the positions of simple sequence repeats at the gene and related transcript sequences different? I'm working on the simple sequence repeat (SSR). I found just one region (about 21 bp) with an SSR motif in a given gene. This gene has multiple transcripts, with the same SSR motif located in various positions of different transcripts. Could you please help me understand how this happened?

Because of Alternative Splicing, suppose an exon occurs neither the first nor the last, then the same exon will come at various positions in different transcripts of the same gene. Thus, if your SSR of interest exists in that exon, you will find the same SSR located in the various positions of different transcripts.


After the primer is removed from the leading strand, how does DNA polymerase I add dNTPs without a 3'-OH? I have a question about replication in prokaryotes. I learned in school that:

DNA polymerase needs 3'-OH to add a dNTP.
The chromosomes of prokaryotes are usually circular.
The primer in the leading strand (of course the primers in the lagging strand too) is removed by the 5'→3' exonuclease activity of DNA polymerase I.

It makes sense that on the lagging strand the primers are removed and then replaced by new dNTPs using the 3'-OH of the previous Okazaki fragment. However, for the primer on the leading strand, there is no Okazaki fragment upstream and thus no 3'OH that DNA polymerase can use for polymerisation.

How is the primer replaced by new dNTPs on leading strand?

The leading strand post-initiation
First consider the DNA replication fork after initiation has occurred.
The 3′-OH primer on the leading strand is the 3′-end of the strand of DNA being synthesized in the 5′ to 3′ direction (circled in the diagram below, modified from Berg, Biochemistry). It is not removed because there is no need to do so. (The primer on the lagging strand is only removed because it is RNA.) So the problem posed in the question does not arise.
Remember that the reason for Okazaki fragments is that there is no DNA 3'-OH primer for the lagging strand, so a temporary RNA 3′-OH primer is generated instead, RNA polymerase — unlike DNA polymerase — is able to copy DNA without a primer. There is no such problem for the leading strand.

The leading strand at the origin of replication
As @canadianer points out in a comment, the remarks above do not apply to the initiation of DNA replication, the single instance where the leading strand must have an RNA primer. In the case of prokaryotes such as Escherichia coli replication proceeds in both directions so that a short time after initiation one has a replication bubble as shown in the figure below (adapted from Russel, iGenetics) :

It can be seen that, at the origin, the 3′-OH of the DNA from the lagging strand of the other direction of replication (boxed in red) can act as a primer for the DNA synthesis function of DNA polymerase I, after its exonuclease activity has removed a nucleotide from the start of the RNA primer on the leading strand.
References
Berg et al. Ch.27
The Cell, Ch. 5
Sandwalk: Blog page
Footnote
There was a typo in the original question which caused confusion about which strand the poster was concerned with. This answer assumes the leading strand.


How does HIV know to attack specific immune system cells? I'm no biologist, but curious of the answer to which I could not find online.
How are Human Immunodeficiency viruses able to detect and distinguish immune system cells with a CD4 receptor on the surface from other cells in the body, in particular other immune system cells without the receptor?
If I have asked the question on the wrong platform, please inform me otherwise.
Thanks

The CD4 receptor is a protein complex that harbors very specific chemistry. A virus is able to bind with the receptor if it harbors a particular protein/set of proteins that are able to interact with the receptor. The virus is basically disguised as something the CD4 receptor recognizes, and from there it is internalized within the cell via a process called endocytosis. You can google viral endocytosis to learn more.


Why do neurons have a negative resting potential? Neurons expend the majority of their energy powering ion pumps to maintain the chemical gradients that power their electrical activity. To have a negative resting potential, neurons leak potassium across the membrane, which seems like a terrible waste of energy to me. I would like to know what benefit a neuron receives in exchange for this seemingly unnecessary metabolic load.

I am not asking how the resting potential is achieved. I am also not interested in the trivial answer: that the voltage-gated channels are configured to require a transition across the -40mV or so threshold in order to fire an action potential. It seems to me that this threshold is arbitrary; if there was no advantage to maintaining this gradient then neurons would have evolved to avoid it.

Any ideas? Or better yet, pointers to places where this has already been answered?

My best guess so far looks like this: The total range of available voltages is more-or-less fixed from -90 to +50mV. We want to avoid getting too close to either end, since the channels become less effective near their reversal potentials, so maybe the effective range is more like -70 to +30 (to go outside that range, we must sacrifice speed). Within that 100mV range, we leave the bottom 30mV or so for EPSP integration, and the other 60mV for action potentials.  Now, if the resting potential was 0mV, the available dynamic range for integration and spiking would be much smaller which probably translates to making the output noisier.

Essentially all animal cells maintain an ionic balance causing a resting potential of about -70 mV in order to maintain their internal environment including pH, ion concentrations, osmotic pressure and volume. (Lodish, Molecular Cell Biology)  Neurons developed from existing types of cells and it's unlikely that the cost of maintaining resting potential in the neuron could have driven evolution of an entire alternative system to provide the homeostasis supported by the existing system.

Note that the depolarization of the membrane at any particular place during an impulse is very short so the impact of the ion flows have only limited effect on the cell's overall internal environment beyond requiring adjustment by ion pumps for the losses involved.  It also is not obvious how the wave-like characteristic of a nerve impulse could be generated if the membrane did not carry a nonzero potential; there would be no stored energy (in the form of ion gradients) available to make the pulse swiftly spread across the membrane.

Another point to consider is that the perhaps 15% of a neuron's energy spent on replacing leaking ions may have some hidden usefulness.  This paper suggests that neurons may actually be set up to leak at a rate higher than they would if it were minimized.


What is the mechanism by which bactericides kill bacteria? "Bactericides kill bacteria". What is the meaning of "killing" in this context, and how exactly is this "killing" happening chemically?

Each bactericidal agent has a different mechanism of action. For example:

Alcohol denatures proteins necessary for function and the lipids in the plasma membrane dissolve into the alcohol.
"Iodine can penetrate the cell wall of micro-organisms quickly, and the lethal effects are believed to result from disruption of protein and nucleic acid structure and synthesis." [CDC]
other mechanisms include tampering cell metabolics, tampering DNA replication, and more.

See also:

The 2008 CDC guidelines for sterilization and the such for healthcare settings. Each method will contain a comprehensive description along with a statement of "mode of action," i.e. how the method actually kills the bacterium.
Another good link here from the CDC examines factors affecting the efficacy of sterilization.

Otherwise, it would be best therein to split the specific mechanisms you perhaps don't understand into separate questions. But an important take-home message in the efficacy link above just adds to just how broad this question is:

  Microorganisms vary greatly in their resistance to chemical germicides and sterilization processes.


Clarification on Hatch and slack pathway The following is a minor clarification that I want to make, since it is rarely addressed directly in most of the texts I have gone through.

In C₄ pathway, the chloroplasts are dimorphic, that is, the bundle sheath chloroplasts contain RuBisCO, but lack grana and can hence perform only the light-independent reactions. The mesophyll chloroplasts lack RuBisCO but contain the granal apparatus to perform light reactions for synthesis of ATP and NADPH. The bundle sheath cells are impervious to gaseous transport (to prevent the entry of O₂), but recieve the required CO₂ by the intake of an organic acid produced by CO₂ fixation by the mesophyll cells.

  But, to effect the Calvin cycle in the bundle sheath cells, it
  requires a high concentration of the light reaction products, i.e.,
  ATP and NADPH. Since they themselves lack grana, they must obtain the required share from elsewhere. Where do they obtain it
  from?

My guess is that NADPH enters the bundle sheath cell with the organic acid primarily produced in the mesophyll cells where light reaction occurs. ATP is met by a similar uptake plus the utilisation of the ATP produced by respiration. I need to confirm this as it is usually never addressed in texts.

I am not sure about the source of ATP but I can tell you something about NADPH.

The conversion of malate to pyruvate and CO₂ by malic enzyme is carried out in the bundle sheath cell. This process produces NADPH.


What is it the most common reason for community acquired pneumonia? This is a difficult question because there are many types of community-acquired pneumonia (CAP): typical acute, atypical acute and chronic.
Most common microorganisms are also different among different groups: children, adults, elderly, immunocompromised and people at risk of different diseases.

Some options:

Streptococcus pneumoniae
Hemophilus influenzae
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
bronchiectasis
Chlamydia pneumoniae

Not any virus, since they are present in only about 20% of diseases.
Streptococcus pneumonia is probably a good choice.

What is the most common reason for community acquired pneumonia?

You are right in that there are several ways to split down CAP, and plenty of different pathogens to look at.  But then we are looking for the most common.  Pnumonia is most common in children and adults over the age of 75 (or 65 depending on who's counting).  Luckily there are plenty of good reviews for both populations.
From the pediatric side we have Iroh Tam PY(1):

Pneumonia occurs more often in early childhood than at any other age,
with the exception of adults older than 75 years, and kills more
children than any other disease worldwide

As far as pathogens:

Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) have
been characterized as 2 bacteria predominately responsible for cases
of fatal pneumonia in children.  However, widespread introduction
of Hib and pneumococcal conjugate vaccines has led to significant
declines, especially of Hib, although Streptococcus pneumoniae is
still the predominant bacteria isolated from bacterial CAP in
children.  There is increasing recognition of the prevalence of mixed
bacterial and viral infections, which have been documented in 23% to
33% of cases of pneumonia.

Then we move to the geriatric side of things with Falcone et al (2):

Common pathogens include H. influenzae, enteric gram-negative bacilli,
the atypical organisms, S. aureus, Pseudomonas aeruginosa, and M.
catarrhalis, although the relative prevalence of each tends to vary
among studies. Among elderly individuals with aspiration pneumonia,
gram-negative bacilli are the predominate organisms (49 %), followed
by anaerobic bacteria (16 %) and S. aureus (12 %).

Though I should note, having done them myself, getting accurate cultures is difficult, and viral levels a very likely to be under reported because of handling and skill.

For example, in different prospective studies in which the
microbiologic etiology of CAP was systematically sought in the
elderly, a definite or presumptive pathogen was often reported in <60
% of the patients. (2)

And again in children:

There are 2 main challenges in the diagnosis of CAP: the first is the
definition of CAP, particularly in young children, in whom bacterial
and viral infections can occur with similar frequencies, and in whom
overdiagnosis of mild symptoms and signs may lead to unnecessary
antibiotic use; the second is the identification of a causative pathogen, which is frequently impractical and inadequate in children, and
in whom the failure to isolate an organism can result in unnecessary
antibiotic use. (1)

Taking into account more global sources, I'm actually thinking Hib infection has dropped more due to vaccination than I gave it credit for, putting my bet on S. pneumoniae, and showing my regional experience may not be representative (3, 4, 5, 6).
(1) Iroh Tam PY. Approach to common bacterial infections: community-acquired pneumonia. Pediatr Clin North Am. 2013 Apr;60(2):437-53. doi: 10.1016/j.pcl.2012.12.009. Epub 2013 Jan 12
(2) Falcone M. et al. Pneumonia in frail older patients: an up to date. Intern Emerg Med. 2012 Oct;7(5):415-24. Epub 2012 Jun 12.
(3) Brown JS. Community-acquired pneumonia. Clin Med. 2012 Dec;12(6):538-43.
(4) Kurutepe S, Ecemiş T, Ozgen A, Biçmen C, Celik P, Aktoğu Özkan S, Sürücüoğlu S. [Investigation of bacterial etiology with conventional and multiplex PCR methods in adult patients with community-acquired pneumonia]. Mikrobiyol Bul. 2012 Oct;46(4):523-31.
(5) Tao LL, Hu BJ, He LX, Wei L, Xie HM, Wang BQ, Li HY, Chen XH, Zhou CM, Deng WW. Etiology and antimicrobial resistance of community-acquired pneumonia in adult patients in China. Chin Med J (Engl). 2012 Sep;125(17):2967-72.
(6) Capelastegui A, España PP, Bilbao A, Gamazo J, Medel F, Salgado J, Gorostiaga I, Lopez de Goicoechea MJ, Gorordo I, Esteban C, Altube L, Quintana JM; Poblational Study of Pneumonia (PSoP) Group. Etiology of community-acquired pneumonia in a population-based study: link between etiology and patients characteristics, process-of-care, clinical evolution and outcomes.  BMC Infect Dis. 2012 Jun 12;12:134. doi: 10.1186/1471-2334-12-134.


Taq Polymerase's stability at high temperature I was asked a question as to what is so special with Taq Polymerase that makes it quite stable at high temperatures though its functioning is the same as other DNA polymerases like that of mesophiles.

I just think it's the adaptation of that particular bacteria in that high-temperature environment. But I want to know if there is any strong reason for this stability.

Well, the evolutionary reason is the one you mentioned: the thermostability of Taq allowed its bacterium to colonize high-temperature environments. That, however, does not say anything about the molecular reasons for this difference.

I found this very good answer on Quora. The end of the post has several references for its claims.

Long story short, the stability of a proteins folded state depends on the difference of free energy $\Delta G$ between the folded and unfolded states. However, $\Delta G = \Delta H - T \Delta S$, which means the difference in free energy can either come from a bigger difference in enthalpy (for example, salt bridges, hydrogen bonds, hydrophobic interactions and such in the folded state) or a smaller difference in entropy (for example, a low number of "not-rigid" amino acids like glycin , or a high release of water from folding).

While enthalpy is often the reason for stability of folding, it seems like for Taq polymerase the difference actually lies in an unusually small difference in entropy between the two states.

Edit: here is one of the best references of the post. Open the link above to find more. https://www.ncbi.nlm.nih.gov/pubmed/24174290


What attracts cells to: pathogens, professional antigen-presenting cells, and cells with an antigen on its MHC-1 protein? I have a few questions in regards to attraction/stimulation in the immune system.

What attracts leukocytes and antibodies to pathogens in the first place?
What attracts CD4+ cells to professional antigen-presenting cells (APC)?
What attracts CD8+ cells to cells with an antigen on a MHC-1 protein?
What attracts macrophages to pathogens that have been tagged with antibodies?

Is it just a case of everything bumping into each other and if cells (and antibodies??) bump into chemokines and/or cytokines they will be stimulated (and not attracted) to stay around that area moving to an area of a greater concentration of chemokines and/or cytokines?

That said point 1 can occur without chemokines and/or cytokines (in the case of antibodies, they could be taken/administered by the person).  While in case of point 3, (I may be wrong here) but chemokines and/or cytokines may not be present in the case of MHC-1?

What attracts leukocytes and antibodies to pathogens in the first
  place?

They just bump into them. If secreted antibody is already present in the blood then complement system can be activated.

  What attracts CD4+ cells to professional antigen-presenting cells
  (APC)?

APC release chemokines. All that is known is that this is a CC-type chemokine and signals via CCR4/CCR8 receptors. See this list of articles (from Google Scholar). This study reports a peptide called Chemrin that promotes chemotaxis via ChemR23 receptor.

  What attracts CD8+ cells to cells with an antigen on a MHC-1 protein?

CD8+/NK cells are activated by CD4+ cells before they kill their target. The MHC-1+antigenic peptide is just a mark for the cells that are to be attacked, as far as I understand.

  What attracts macrophages to pathogens that have been tagged with
  antibodies?

Complement factors.

NOTE: Many of these concepts are old but still relevant. You should check out recent articles in this area for novel/atypical mechanisms.


Does a tubular sodium reabsorption cause a stimulation of β2-adrenergic receptors? I read the study "The Role of Aldosterone in Obesity-Related Hypertension" and there is one thing I didn't understand. They write: "According to norepinephrine-induced tubular sodium reabsorption, stimulation of β2-adrenergic receptors leads to activation of the Na–Cl cotransporter through suppression of the serine-threonine protein kinase WNK4 in the distal tubule." Is According to meant like due to? So does a tubular sodium Reabsorption cause a Stimulation of β2-adrenergic receptors?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886496/

You've got it backwards. "norepinephrine-induced tubular sodium reabsorption" is the whole process. The β2-adrenergic receptors respond to norepinephrine (this is the "norepinephrine-induced" bit). The receptors then suppress WNK4 in the distal tube ("tubular"), which causes the Na-Cl cotransporter to activate, which in turn causes sodium reabsorption.

This was probably a poorly phrased sentence on the part of the writers, but the sentence follows the same logic as "According to the First Law of Thermodynamics, energy cannot be created or destroyed". The description of the process is just complicated by multiple clauses.


Do biological facts determine when a human fetus is considered alive and human? I often hear or read this statement:

  "It's not a human, it's a fetus."

In other words, some think a fetus is non-human until a certain point.

And another similar statement:

  "The fetus isn't alive until 26 weeks of gestation."

So some think the fetus is not actually "alive" until a certain point.

What does biology have to say about these two statements?

I encounter these statements often in discussions about abortion, but that issue, and other similar philosophical issues, are outside this question. I'm wondering strictly from a scientific/biological standpoint: are these statements true?

Is the fetus in a human mother non-human until a certain point?

Does the fetus not classify as "alive" until a certain point?

The people I encountered truly believed these statements (3 of the 4 in mind also claimed science was on their side), so it's not as if the question has no merit. I assumed that in the realm of science and biology, there must be a convincing and sure answer.

Life is generally distinguished from non-life by metabolism and growth. As such, a fetus is alive. The reference to "not...until 26 weeks gestation" that you've heard likely refers to viability.* With the most aggressive medical care, this is the approximate age when a fetus may be able to survive outside the womb.

The term human from a biologic perspective is a species label.** Given that a fetus is genetically indistinguishable (in broad strokes) from a post-natal human, I think it would be hard to argue that it is anything other than human.

Summary: Yes, a human fetus is both alive and human.

*Note that this use of the word viable is standard but deviates somewhat from the etymology of the word.
**I'm ignoring here other ancient species (homo-) which may be considered human but are irrelevant to the question.


Identity By Descent vs Identity By State Background

The concepts of Identity By Descent (IBD) vs Identity By State (IBS) are central in population genetics, yet I fail to fully wrap my head around the definitions.

You can find examples where my understanding of IBD vs IBS is quite poor in @DermotHarnett's answer here or in the comments with @PaulStaab here. @PaulStaab suggests that different authors have used different definitions of IBD and IBS.

What is unclear to me

From what I remember from Hartl and Clark (I don't have the book with me to quote), IBD depends on an arbitrary time threshold in the past beyond which if coalescent events occurred, then we still call the two alleles IBS (Identical by state) and not IBD. The idea that the concept of IBD depends on an arbitrary threshold bothers me though!

I suppose that two alleles can be IBD without being IBS in the case where a mutation or recombination event in the middle of the sequence of interest prior (looking backward in time; more recent) to their coalescence. I suppose two alleles can be IBS can not be IBD only if we use an arbitrary threshold that is older than their coalescent time or if convergent/parallel evolution happened.

Questions

Does IBD depends on an arbitrary threshold?
Are there several definitions of IBD and IBS in use?
Does IBD implies IBS?
Does IBS implies IBD?
Can you please make a short review of these definitions to clear things up?

The issue of IBD and IBS can indeed be confusing.

The identity by state definition refers to the fact that at some point two individuals, even if they are not related to each other, present the same allele at a specific locus. Because of their un-relatedness this similarity probably arose from a similar mutational event.

On the other side, with IBD two individuals happen to share the same allele because of their coancestry.

Alleles that are identical by descent are also identical by state. But the opposite is not true. (see also https://www.biostars.org/p/174048/#174049 and Powell et al 2010, Nature Reviews Genetics 11, 800–805 (1 November 2010) | doi:10.1038/nrg2865).

Now, about the threshold that you were mentioning in your question, I am not entirely sure what you mean. Eventually, all individuals are traceable to a MRCA (most recent common ancestor). So, I think the threshold you talk about refers to the size of the population in analysis. Depending on the size of your population you will have different proportions of alleles that are IBD and IBS.

Hope this help.


Genetic engineering for insulin production In order to put human DNA inside a bacteria in order to have it create Insulin, from what type of cell would you need to take the gene for insulin?
I thought it should be from any somatic cell, since the DNA is identical, but I'm told it should be only from the pancreas, why is that?

In short, because the easiest way to get the protein coding sequence of the gene is to create cDNA based on the mRNA, and insulin mRNA is only expressed in pancreatic cells.

Insulin gene consists of two exons. That means, amplifying the genome will not give us a coding sequence -- two pieces of that sequence will be interrupted by a large, non-coding intron.

On the figure above, you see the translated (i.e., coding a protein) sequences represented as opaque boxes. They are linked by a slightly curving thin line -- this is a fragment of sequence that will get excised during mRNA maturation.

To get the coding sequence in a straightforward manner, one can create cDNA from mRNA using a reverse transcriptase. Processed mRNA does not contain the intron. And clearly, pancreas cells express the insulin gene mRNA at very high levels, enabling such a procedure, whereas it is practically not expressed by other tissues.

EDIT: Since I see these comments upvoted, I need to debunk them here:

There are introns and splicing in both, bacteria and archea. Both type I and type II introns are present in bacteria. See this review on bacterial type II introns.
Bacteria also have post-translational modifications, including glycosylation. Once thought to be rare, there is an increasing body of evidence that it plays a much more important role than previously thought. See a paper from a decade ago here.


DNA ligase mechanism I am unable to understand what happens to the phosphates from  ATP. What are they used for ?Charging 3' end or 5'end ?

When you ligate two strands of DNA you build up a phosphodiester bond. To do so, you need energy, and this energy for the DNA ligase comes from the ATP (in bacteria this energy can also come from NAD+.
The enzyme metabolizes ATP to AMP + PPi and binds the AMP in its active center. Then the AMP is involved in the reaction itself and released afterwards. This page has a few illustrations on this process.
If you want to dive really deep into the topic, have a look at this review:

Eukaryotic DNA Ligases: Structural and Functional Insights


What kind of an animal is that? Found in Austria. At half past nine p.m. in the summer/autumn.

Due to the long legs and the shape of the abdomen, this is probably a crane fly, a dipteran from the Family Tipulidae.

Just for comparisson, here is Holorusia hespera:

Crane flies can be very large. I still remember the first crane fly I saw, in New Zealand: it seemed like a humongous mosquito (mosquitoes are dipterans from a different family, called Culicidae), it was quite impressive. Have a look at the size of this crane fly:

Despite their scary size, do not fear them. Unlike mosquitoes, crane flies are completely harmless: adults have a short life span, only days (just enough to reproduce), and in most species of crane flies adults don't eat at all.

Regarding the exact species of your specimen: the number of species in Europe is huge and, together with the fact that your photo is not the best one, it will be very difficult narrowing this down to Species, or even to Genus. Therefore, a better photo is necessary.


Pyura DNA extraction I'm am struggling with genomic DNA extraction from different samples of Pyura chilensis; the DNA is degraded as can be seen on the gel.
We've always used GeneJET Genomic DNA purification Kit (by ThermoFisher), and it works fine for samples from other species; so the kit isn't the problem.
We've always used tissue samples stored in 95% Ethanol (which are washed with water prior to DNA extraction), but the problem persists irrespective of whether the samples are one day old or a few years old.
The storage method seems to work fine for gDNA extraction from other species.
Then, my guess is that the problem is with Pyura itself. So I have to figure out if either the extraction or the storage isn't appropriate for Pyura. I read that Pyura has a lot of copper in it. We planned to use a new buffer for storing it: salt Saturated DMSO, containing EDTA.
I would like to ask if any of you have ever worked with this organism (and if you have, then how did you manage to extract DNA from it). Do you have any suggestions on any DNA purification protocols?

1st lane is the ladder (1kb) and last 3 lanes with long blurred thing instead of bands are my DNA samples.

With reference to your gel photo, the genomic DNA (in the three Pyura sample lanes) does not look badly degraded.  If the size marker is 1 Kb ladder, then the majority of the DNA is of high molecular size. During extraction it is common for high molecular weight DNA to become "sheared" to some degree (mechanically broken into smaller fragments). This can appear as the faint downward smear. The lanes may be somewhat over loaded as well. You can try to use more gentle extraction technique and see if it helps to your satisfaction. Any of those you mention will work.

Badly degraded genomic DNA would appear as a more intense "smear" near the lower portion of the 1 Kb size standard.


Is there a database for immunoglobulin domain structure? is there a database where I can find the sequences of the hypervariable domain of immunoglobulins and the sequences of the related antigens? Thank you

There are a number of databases that exist, though the one you would want to use will likely depend on what you need it for. The one that's recommended at my university is IgBlast, associated with The National Center for Biotechnology Information (NCBI), however I've seen IMGT as a recommended source, as well; it seems to have a wider array of tools. That being said, I can't say which you might find more beneficial, as I'm uncertain as to how you'd be using the resource.


What are the psychedelic effects of (star) anise and how many people are affected? Backstory:

My girlfriend reacts heavily to chocolate and drinks containing stellar anise, in a way that seems comparable to psychedelic drugs.

After consuming it, it takes approximately five minutes for the reaction to become apparent.

Observed Effects:

Due to the heavy reaction, she tends to avoid these foods, however, we could observe the following effects:

Heavy giggling, occasional outbursts of loud laughter;
Much less frequent: Crying (just kind of starts from the giggling and subsequently fades back into giggling);
Minor hallucinations (Sparkling hair, glowing faces);
Loss of motor skills, especially balance;
Feeling time pass much faster (to her, a 15 minute episode felt like 1-2 minutes, an hour like 5-10 minutes);
Some memory loss (probably related to the time perception?);
Unfocused mind;

Her speech remains clear and articulate.

Observations are anecdotal, as I only observed two episodes, and we realized what happened only after the first.

Googling Results:

Apparently, around 1-3% of humans react in some way. However I couldn't find any detailed explanations of the hows and whys, nor any actual research.

I am very curious about this. Is it dangerous? Are there any related effects (genetic disorders, maybe?). All explanations, and hints how to google better, are welcome.

Interesting question! As this post has been sitting around for a while I am going for some speculations. First you talk chocolate, which essentially contains the alkaloid theobromine. Anise contains the propenylbenzene (E)-anethole (Idle, 2005). Theobromine is a caffeine-derivative and basically produces alertness, but also restlessness and perhaps anxiety when administered in large amounts (wiki). In extremely high doses there can be LSD-like effects (anecdotal report). Perhaps (speculative) your girlfriend is especially sensitive. Then (E)-anethole: the late Alexander Shulgin, Godfather of MDMA, has made the etheric oils (in)famous as precursors for amphetamine synthesis. In themselves the propenylbenzenes like (E)-anethole are quite harmless, as they do not contain an amine group (a prerequisite for being called an alkaloid). However, heating (E)-anethole in the presence of ammonia may lead to the production of PMA, a compound structurally and neuropsychopharmacologically related to MDMA (Idle, 2005). Although a bit of chocolate and a sip of Sambuca do not meet any of these conditions, both chocolate and Sambuca do contain certain psychoactive compounds, or their immediate precursors.


What kind of (cinnamon?) tree is this? This tree was found in the rainforest on subtropical Japanese islands. At first I thought that it was a camphor tree, which are indeed common in Japan. However, the leaves are slightly different and elongated, and the fruit  has a sharp tip and is much larger than that of camphor trees. The bark is very aromatic and smells like good cinnamon, perhaps a bit peppery. Any ideas?

This is the Japanese cinnamon, Cinnamomum tenuifolium, or "Yabu Nikkei" in Japanese. It smells like cinnamon and is found from the middle of Honshu (Fukushima prefecture and southward) throughout Shikoku, Kyushu, Okinawa, and into China. It is the native and more commonly found cinnamon species in Japan that grows wild in forests. The other species is Cinnamomum sieboldi, which was introduced to Japan in the early 18th century from its native Indochina via China. C. tenuifolium is distinguishable from C. sieboldi by its much more symmetrical arrangement of leaves, as depicted in your photograph.

This page also details the differences and similarities to other related species in Japan, however it is only in Japanese:

Camphor/Cinnamon species in Japan.


how can a recessive allele become represented in a significant number of individuals in a population Darwin believed that individuals that are poorly adapted to their environment are less likely to survive and reproduce. This means that their genes are less likely to be passed to the next generation. Given enough time, a species will gradually evolve.

-individuals in a species show a wide range of variation
this variation is because of differences in their genes

-individuals with characteristics most suited to the environment are more likely to survive and reproduce. The genes that allow these individuals to be successful are passed to their offspring.

In genetic terms, evolution is any change in the allele frequency of a population.

A recessive allele can become represented in a significant number of individuals in a population, how?

A recessive allele is one whose phenotype can be masked by a dominant allele. A recessive allele is not necessarily deleterious, and the dominant allele does not necessarily have higher fitness than the recessive allele. Fitness and dominance are often confused, but they are not the same thing.

In some scenarios, the recessive allele indeed confers a fitness benefit, and when it does, it is predicted to increase in frequency rapidly because homozygous recessive individuals have higher fitness than both homozygous dominant genotypes and heterozygotes.

A recessive allele can also persist in a population if it is deleterious in homozygotes but confers a heterozygote advantage. The most famous example of this phenomenon is in Africa, where individuals heterozygous at the sickle cell locus have a fitness advantage because they are resistant to malaria. A higher prevalence of sickle cell phenotypes occur because selection for heterozygotes maintains a high frequency of recessive alleles in the population. For more, see Templeton (1982, http://www.indiana.edu/~curtweb/L567/readings/Templeton.pdf) and Allison (1954, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2093356/).


Synaptic connectivity in the newborn's brain In my understanding, learning is related to the strengthening and weakening of synaptic connections. Very roughly said: Synaptic connections that are used often are strengthened, those that are used rarely are weakened. This is basically the Hebb rule.

Assumed that the Hebb rule holds at least partially (of course, there are other factors at work during learning), I wonder if in a newborn's brain the areas where learning will take place are equally weakly connected by synapses (so the pathways will be "built up") or are equally strongly (maximally) connected (so the pathways will be "carved out") or something inbetween. Or are there areas of both/all kinds?

(I assume that there is a maximal connection strength beyond which no further strengthening takes place.)

I wonder if in a newborn's brain the areas where learning will take place are equally weakly connected by synapses (so the pathways will be "built up") or are equally strongly (maximally) connected (so the pathways will be "carved out") or something inbetween. Or are there areas of both/all kinds?

According to a paper authored by Princeton researcher Deborah Sandoval:

  At the time of birth, the human brain consists of roughly 100 billion neurons in the cortex (The University of Maine, 2001). During the early stages of development (between infancy and adolescence), the weight and size of the brain increases significantly (by up to a factor of 5). This increase in density is not contributed to the creation of a large number of new neurons (neurogenesis), but rather an exponential increase in synaptic growth, known as exuberant synaptogenesis (Huttenlocher & Drabholkar, 1998). At infancy, each neuron averages around 2,500 synapses, and at the peak of exuberant synaptogenesis (around 2-3 years of age) the number increases to around 15,000 (The University of Maine, 2001).

..

  Shortly after this period of synaptic growth, the network experiences a decline in synaptic density as neuron connections that are used least-often are removed from the network. The process of eliminating/weakening the irrelevant and inefficient synapses during this developmental period is known as synaptic pruning. Synaptic pruning has been viewed as a learning mechanism, where the “pruning” or removal of a synapse is dependent on the neurons’ responses to environmental factors and external stimuli (Craika & Bialystokb, 2006). The processes of synaptogenesis and synaptic pruning in the developmental stages of the brain have been associated with an individual’s “critical period,” a time where an individual is highly receptive to environmental stimuli and, therefore, learning (Drachman, 2005).

Given the claims in those passages, it would seem that learning (for infants) takes place by initially developing an extremely large number of neuronal connections (most likely due to massive information exposure), and then selectively prunes synaptic sites due to a lack of various external stimuli keeping those axons/dendrites/synapses active; the remaining connections are then reinforced (continously excited). So, as you put it, it would seem that the infant brain both "builds up" and "carves out" neuronal connections for the sake of learning.

To further support this idea though, consider the following fMRI images that depict the functional connectivity of an infant's brain for the first year of life. (Function Connectivity of the Infant Human Brain)

Pay special notice to the coloration differences between rows, within a given column, for the infant (first five rows). With dark red being least functional, and bright yellow being most functional, it can easily be seen that, as the infant gets older (is learning), occurrences of yellow tend to form as clusters within regions of red, which indicate locations of highest functional network activity.

If you then continue this pattern and compare the most functional regions belonging to the 12 month infant scan, with that of the adult (bottom-most row), you can see that the concentrated yellow regions in the infant scan become the general (red) functional regions in the adult scan. This only further suggests that those initial, yellow-denoted functional regions (belonging to the infant), matured into the even more dense, functional regions of the adult brain, through the process of pruning unnecessary connections (which creates smaller functional regions), while at the same time increasing signaling strength amongst neighboring neurons (synaptogenesis).

Lastly, to assess the initial strength of each neuronal connection for an infant brain: when looking at the 1-month old scans, it appears that most all regions of the brain have a color that falls within an associated numerical range of .4 to .8, which would suggest that the brain, as a whole, begins at an almost "neutral" state.


Is it possible for bacteria to acquire family-wide antibiotic resistance? If there is bacteria, lets say Enterococci that is sensitive to:

Amoxycillin-Clavulinic acid
Ampicillin-Sulbactam
Ofloxacin
Ciprofloxacin

Is it possible to become resistance to Ampicillin-Sulbactam by using Amoxycillin-Clavulinic acid ?

Is it possible to become resistance to Ofloxacin by using Ciprofloxacin ?

The two amoxycillin formulations you mention pair the amoxycillin with a Beta lactamase inhibitor. This is because of the prevalence of resistance to beta lactam drugs including amoxycillin. If we were to invent a brand new never before seen beta lactam drug and started using it irresponsibly, there would probably be resistant bacteria within 5 years. The same beta lactam core structure that makes the drugs work against the peptidoglycan synthesis machinery make it susceptible to attack by beta lactamase. A new beta lactam could avoid the lactamase for a while, but the same evolutionary pressures that selected for resistant mutants against the other beta lactams would select for mutants resistant against the new one.

The same goes for the fluoroquinolines you mention. Their mechanism of action is different, they inhibit DNA synthesis by blocking topoisomerase II activity. But once a bacterial strain is selected for that has resistance against one member of a class of antibiotic it's relatively easy for it to acquire the mutations that confer resistance against other members of the class. Changing the structure of the drug enough so that cannot be defeated by the mechanism of resistance while retaining the drugs mechanism of action is probably impossible, or at least we haven't done it yet. Even vancomycin, one of our most powerful antibiotics, has some bacteria resistant to it.


How far into a pregnancy is it before visible signs of it is apparent and risk of physical trauma increases I'm doing research for a series I'm writing. in it the main character is pregnant however goes off to fight a criminal organization who have been killing her friends and i want her appearance to show that she may not be pregnant however she fights and defends as if she is mindful of heavy impacts could cause a miscarriage

I am wondering how far into a pregnancy is it before visible signs of it is apparent and risk of physical trauma causing miscarriage increases, if there is also a point during the pregnancy where the fetus could mutate via outside interference then that would be good to know too however I can go without that information.

NOTE: I want to know this information so that even though the world in this series I'm writing is totally fictional, one can begin to question how fictional it really is when some parts are based off actual science and logic of real life.

Around the second trimester.  That's an article from WedMD, which says quite a few things.  To summarize, by the end of the first trimester:

  You may be noticing some of the first physical signs of pregnancy: breasts that are sore or tingle at the slightest touch, skin that's drier or oilier than usual, and "morning sickness" -- which may or may not restrict itself to the morning hours. As many as 70% to 80% of pregnant women have it, but not feeling morning sickness doesn't mean there's anything wrong with the baby.

In the second trimester:

  Most pregnant women begin to "show" during the second trimester. You likely gained less than 5 pounds during your first trimester, but now the number on the scale is edging relentlessly upward. As your second trimester proceeds, you'll gain an average of 1 to 2 pounds per week.

The exact time and rate of "showing" can vary, including whether or not this is your first pregnancy.  By the third trimester, the infant is rapidly becoming more and more capable of surviving on its own.


Measurement of glucose concentration in the human brain If I want to measure the exact glucose concentration in a human brain then how can I proceed to do that? Is there any technique or assay to do that?

It is possible by using 13C NMR Spectroscopy.

It has been done after infusing enriched D-[1-13C]glucose in six healthy children. The results showed that at euglycemia glucose concentration is about 1 micromol/ml.

Source: Gruetter R, Novotny EJ, Boulware SD, Rothman DL, Mason GF, Shulman GI, Shulman RG, Tamborlane WV. Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy. Proc. Natl. Acad. Sci. U.S.A. 1992 Feb 1;89(3):1109-12. PubMed PMID: 1736294.


Parallels between pixelized image and the human retina On Wikipedia it is explained that the human eye has a certain 'resolution'. Does this mean that the retinal image consists of pixels? If yes, what shape would these pixels have?

The pixels of the visual system are represented by the photoreceptors. Their shape is the following (adapted from "The Brain from Top to Bottom, MgGill University"):

There are about a 180 photoreceptors packed on 288 microns on the retina (see "What's the smallest size a human eye can see?") so about 1 pixel per 2 microns. The rods and cones are packed closely together on the retina, referred to as the retinal mosaic. This retinal mosaic is not unlike a photosensitive chip, as can be seen on the folllowing image (Developmetal Neurobiology lab, UCLA, Santa Barbara):

We do not visually perceive this mosaic, as the optics of the eye (e.g., light diffraction by the cornea and the lens, and distortions due to the relatively large pupil size) prevents optimal use of the photoreceptor density (the maximal resolution). Furthermore, especially outside the field of view (the foveal region), the output of many photoreceptors are funneled onto one single optic nerve fiber, thereby fusing the output of many photoreceptors (See the question "Why can we not see around our point of focus of our eyes?"). Lastly, the brain actively 'glues' any gaps in the visual field together. Most strikingly, the blind spot, which is the place where the optic nerve exits the eye is fairly large, is normally not visible to us: see the following picture (PNAS online content):

Hence, any gaps in the retinal image are in fact actively smoothened out by the brain.


What is the difference between a spore and a cyst? Last year I read a course in biology. During that course I learnt that Protozoa like Lamblia intestinalis or Entamoeba hystolitica form cysts in unfavourable conditions.

This year I read a course in microbiology. I learnt that bacteria like Clostridium perfringens or Bacillus anthracis form spores in unfavourable conditions. So far so good. But then I learnt that prokaryotic Borrelia burgdorferi can form a cyst, not a spore.

Firstly, I would highly appreciate any comments that would cast some light on these terms.

Secondly, I would also like to know if the spore inside, say, B.anthracis is the same organism as B.anthracis that produced the spore. Does a spore and the bacteria that produced it have the same DNA sequence? In other words, if I were a sporeforming bacteria, would my spore be myself, my bodypart or my child?

The bacterial spores you are referring to are called endospores. The spore is formed during unfavorable conditions, by duplication of the bacterial chromosomes, and consequent envelopment by various membranes and protective coatings (while still within the original cell). The spore is dormant and remains so as the outer cell degrades during harsh conditions, releasing the spore. I guess I'd call the spore a clone of the original?

You may enjoy reading the relevant sections in this book, which go into greater detail.

edit: as Souvik has pointed out, this is only one type of "protective" spore. Actinomycetes also form spores, via differentiation of the cells, and cyanobacteria form akinetes also via differentiation (but this structure is not as durable as endospores).

Information about cyst formation is difficult to find, but in bacteria it appears to develop via changes in cell wall composition.


A compound was proposed by error but then showed very good inhibitory properties. How to argue this in a manuscript? In a project, we performed some virtual screening calculations in order to predict inhibitors, and then purchased the compounds and tested them in the lab. One of them was a very good TK inhibitor (IC50 nM).

However, when we processed the results we realized that the presence of this particular compound in the original list of virtual screening hits was due to errors in the original calculations (it was added to the list by random factors, not by docking score).

So now we are writing the paper and we wonder how to argue this. We can not just tell the story like in this post (it was discovered by randomness or by our error). How would you argue this?

Be honest (and possibly split the papers).

If the compound was identified as an error and you want to include in a paper describing the process of your simulation and the effectiveness of the predicted inhibitors, you'd have to do so as a sort of negative control for your calculations (unless there is some way to reproduce/rationalise why it showed up randomly). Since this is the only good inhibitor you have, you'd have to conclude that your calculation isn't much better than chance, or explain why it is better even though you found a better inhibitor by chance. If you have reason to argument that your calculations are good and make sense then exclude the 'random' inhibitor from that paper. You can the write an individual paper about a good inhibitor, the fact that you found it by chance isn't that important anymore.


How does receptor downregulation/upregulation work? My understanding is that if a cell is flooded with a certain neurotransmitter, it may decrease the density of that neurotransmitter. What I don't understand is how.

Is it a direct physical result of the receptor-ligand complex being internalized? I.e., the receptors simply aren't there anymore, because they've been internalized?

Or, does the internalization of specific receptor-ligand complexes actually get sensed by the cell somehow, causing it to produce fewer receptors in the future?

Both internalization (sometimes with degradation) and changes in gene expression can occur; the circumstances leading to the down regulation determine which (or both). It isn't necessary for receptors to be bound to their ligand to be internalized, though, and it isn't the internalization of receptors that causes changes in gene expression (I suppose it is possible that happens someplace, but not that I am familiar with). The processes involve activation of second messenger systems and kinases that either phosphorylate/dephosphorylate the receptors to mark them for internalization and/or degradation, or activate/deactivate transcription factors.

Here are two reviews with more information: one is newer but focused on a single class of receptors and fairly in-depth; the other is a bit dated but more broad, but brief:

Williams, J. T., Ingram, S. L., Henderson, G., Chavkin, C., von Zastrow, M., Schulz, S., ... & Christie, M. J. (2013). Regulation of µ-opioid receptors: Desensitization, phosphorylation, internalization, and tolerance. Pharmacological reviews, 65(1), 223-254.

Tsao, P., & von Zastrow, M. (2000). Downregulation of G protein-coupled receptors. Current opinion in neurobiology, 10(3), 365-369.

You can also read about long term depression, which is different from homeostatic responses to ligand concentrations, but it does seem to serve a homeostatic function to keep overall synaptic strengths from growing indefinitely, and the molecular pathways are very similar (and it is a very well-studied phenomenon so you will find a lot of accessible information).


Histidine - why essential for children? Why is histidine an essential amino acid for children but not for adults ? What changes in the body occur which lead to the formation of histidine in adults but not in children ? What causes these changes ?

UPDATE : Source : Campbell Biology

There are many articles in health literature debating on the question. Everytime the experimental setup seem to me quite basic and I am affraid that one cannot infer many things from these experimental designs. I guess the ethics is limiting much of the medical experimentation (which is good!). Usually it is just the report of observations of what happen to the global health of a patient when one amino acid is missing in their food. Therefore, these articles does not explain much about the metabolism reasons of these needs (which was your question) but only try to define what are the needs. Moreover statistics seem sometimes a bit fuzzy (or absent) to me.

Anyway here is a review of these results and there is a whole paragraph on the question of histidine. The best is that you read it yourself. To make it short: Histidine doesn't seem to be more important to the children than other amino acid. Moreover there is big storage of histidine in our body suggesting that one that is histidine deprived for a while might use these stored histidines.