Healing of Skin Superficial Wound How does the body heal a skin wound without bleeding?
I had a wound in which thick layer of skin was gone and which was too painful to touch. I could see the wound secreting clear liquid rather than forming a scab like in a blood wound. What is this yellowish thick liquid being secreted and does it form new skin?

Skin is composed of layers, the uppermost being the epidermis. Upper layers of the epidermis (dry, flat cells tightly packed together, and of varying thickness on different parts of the body) can be abraded off, leaving deeper layers of the epidermis (nearer to underlying blood vessels) exposed. Since peripheral nerve endings do exist in this area, the wound is painful. A wound that does not extend into the dermis does not bleed (for example, a second degree burn can lift the upper layers of the epidermis from the deeper layers; no blood will collect in the blister, but the wound is painful. Peel off the top of the blister, and you have an analogous situation.

Because the surface of the skin is no longer present, fluid (as with a blister, not containing red blood cells) leaks from the blood vessels. Initially a transudate, it can also be an exudate. And, no, it does not contain the cells needed to regenerate the upper layers of the skin. It contains many of the proteins found in serum and may contain white blood cells which help to fight off infection.

New cells are generated from the deeper cell layers (the basal cells) which are still intact. They grow from the bottom of the wound up, so to speak. The scab formed by the dried fluid keeps the layer under it moist, providing a good environment for cell growth.

Epidermis and Its Renewal by Stem Cells


Identifying whether ELISA kits are authentic or fake What methods can be used to determine whether they are authentic or fake?

You are getting this Elisa Kit spam from China, too? The only way I see, would be to use a known reference standard so you can titrate both the specificity and the sensitivity of the kit. Ideally you would compare it with a known and proven kit. If you have the reference available in the lab and the cheap kit is not too expensive you can give it a try. I would do it, since work time and reagents also cost money.


Why does the pulmonary artery have higher glucose concentration than the pulmonary vein? If the pulmonary artery have higher glucose concentration than the pulmonary vein, does it mean glucose will be consumed during gas exchange?

That confused me because gas exchange is something like diffusion and shouldn't consume any glucose

Gas exchange doesn't but the cells of the tissue it occurs in do consume glucose, even the cells in the walls of the artery will consume some.  The cells in the lungs still need to be fed and only one of those two vessels has flow going into the tissue so it is the one that has to carry that glucose into the tissue.


Would it be possible to force the pineal gland to release dimethyltryptamine on command? To my knowledge, the pineal gland is responsible for the release of dimethyltryptamine (DMT) upon death.  Would it be possible to force the pineal gland to release this DMT while still living?

According to this page the release of DMT upon death is speculative and its presence has so far been confirmed in rodents brain and human melanoma cell line SK-Mel-147. DMT is also produced in humans; however, its production and purpose in the brain has yet to be proven or understood (http://en.wikipedia.org/wiki/Dimethyltryptamine). Hence from what I have gathered on the matter DMT has not yet been proven to get secreted from human pineal gland and its command based secretion is yet to be discovered.


Are gizzard muscles voluntary or involuntary? I started raising chickens this year. They have amazing appetites, and I often wonder what eating is like for them. They have no teeth, so they don't chew their food as they eat it. They do seem to have some sense of taste, because they often bite off a bit of something and then spit it right back out. But the only equivalent of chewing for them occurs in their gizzard. Because the gizzard is pretty far down the digestive tract, I would assume that it's an involuntary muscle. But all chewing being unconscious for them also sounds kind of crazy.

I'm trying to discover the answer to this question on the internet and I'm surprised that the answer hasn't been easier to find. Does anyone here know? Do birds masticate unconsciously?

Involuntary. The gizzard, like our stomachs, works unconciously. However, chickens do choose to peck up stones to help along the process, whether that is by instinct or otherwise. (I raised chickens a long time but a proper reference is below)

This book on commercial poultry raising says involuntary


Generalism - specialism index in microbial ecology I am doing research in Lipid metabolism in different yeast species and I would like to look into ecology of them.

I would like to classify them to a Generalist/specialist based on different Parameters (growth on carbon sources, pH, temperature,...).
I wonder if you have any experiences with that classification and if any of you know which indexes are used for that in microbial ecology?

Thank you very much for your answer!
Martin

I've published a paper comparing different measures of specificity, if that is of any help. But if you plan to have, e.g., measures of performance on carbon sources, pH, and temperature, then you'll have three measures of specificity (i.e. one for each).

Also, worth to have a look at Graham Bell's inconsistency and responsiveness, as used by Venail et al. to classify specialists and generalists.


How does anadromous fish physiology "know" to switch from salt to freshwater and back? What mechanism allows anadromous fish (like salmon) to switch from salt to fresh water and back?  How does the fish "know" to switch its physiology and do other fish possess the biochemical machinery for this?  How difficult would it be to genetically engineer salt tolerance into a freshwater fish?

Osmoregulation is a homeostasis regulation mechanism followed by salmons to adapt on both salt and fresh water.

Osmoregulation is the active regulation of the osmotic pressure of an organism's fluids to maintain the homeostasis of the organism's water content; that is, it keeps the organism's fluids from becoming too diluted or too concentrated. Osmotic pressure is a measure of the tendency of water to move into one solution from another by osmosis. The higher the osmotic pressure of a solution, the more water tends to move into it. Pressure must be exerted on the hypertonic side of a selectively permeable membrane to prevent diffusion of water by osmosis from the side containing pure water.

In order to reduce the dehydrating effects of salt water, salmons drink several liters of water per day, but in fresh water salmons doesn't drinks at all. The only water it consumes is that which goes down when it feeds. When an ocean-dwelling salmon drinks, it takes in a lot of salt(NaCl), which exacerbates the salt-loading problem.
In fresh water, the salmon's kidneys produce large volumes of dilute urine, while in the ocean , the kidneys' urine production rates drop dramatically and produce a very concentrated urine.

Salmon use to deal with the NaCl fluxes driven by the gradients between the salmon and its surroundings. In their gill epithelial cells, salmon have a special enzyme that hydrolyzes ATP and uses the released energy to actively transport both Na+ and Cl- against their concentration gradients. In the ocean, these Na+-Cl- ATPase molecules 'pump' Na+ and Cl- out of the salmon's blood into the salt water flowing over the gills, thereby causing NaCl to be lost to the water and offsetting the continuous influx of NaCl. In fresh water, these same Na+-Cl- ATPase molecules 'pump' Na+ and Cl- out of the water flowing over the gills and into the salmon's blood, thereby offsetting the continuous diffusion-driven loss of NaCl that the salmon is subject to in fresh water habitats with their vanishingly low NaCl concentrations.
Reference

Reference


What kind of changes "stays" in the neuron after the nervous impulse happened? I often see in neuroscience textbooks about how the brain controls everything in the body with different tracts and etc, and it seems that information is always being transmitted, like there's no fixed place in which they are stored. So after the depolarization and repolarization what happens to the neuron itself? Does it depend on which neurotransmitter stimulated it? And extending a bit the question, what is exactly the difference between being stimulated by two different neurotransmitters?(supposed that the neuron has receptors for both and the neurotransmitters are the excitatory type).

TL;DR: There are many ways a neuron can change after a neural impulse happens including calcium influx, long term potentiation and depression, and G-protein coupled receptors. While not an exhaustive list by any means I'll give a brief summary of some mechanisms I know best.
Calcium Entry
There exist calcium channels that open in response to a variety of signals be it voltage depolarization (voltage gated calcium channels), neurotransmitter acetylcholine (Nicotinic-Receptor) or Both depolarization and Neurotransmitter binding (NMDA receptor). There is much more calcium outside the cell than inside the cell. Once inside the cell calcium binds to EF-hands in various calcium-binding enzymes like calmodulin. When calcium binds to the EF-hands of the calmolulin protein it activates and from there can interact with the other enzymes responsible for cell signaling and the effects can be quite diverse depending on what the neuron is responsible for doing and the specific signaling cascade it sets off.
LTP/LTD
I'll focus on the NMDA receptor(excitatory Glutamate/Glycine receptor) in the CA1 region in hippocampus. LTP (or Long Term potentiation) occurs when a synapse (connection between neurons) becomes stronger, meaning the post-synaptic neurons response to the same stimulus from the pre-synaptic neuron is stronger after LTP has occurred. LTD (or long term depression) is the opposite effect where a neuron's response to the same stimulus is weaker after LTD.
The LTP whole process is dependent on calcium entering through the NMDA receptor channel. When both glutamate and glycine are released pre-synaptically they open the channel,  allowing calcium ions to flow into the cell. However, If the voltage in the post-synaptic membrane is too low, Magnesium will get stuck in the channel blocking calcium (and the other ions too!). If the neuron has previously been stimulated and depolarized, by another neurotransmitter/receptor system like AMPA the voltage will be positive enough to pop the magnesium out of place and allow calcium into the cell.
Once calcium is in the cell it is bound to calmodulin which then binds to CaMKII (an enzyme activated by the calcium/calmodulin complex). This will cause a long and complicated signaling cascade which results in AMPA (the other excitatory glutamate receptor in the post-synaptic region) to be phosphorylated causing it to be more active. Furthermore the signaling cascade can cause an increase in AMPA receptor creation and subsequent insertion into the post-synaptic membrane. This of course results in LTP.
Many rules in biology one quickly finds exceptions and caveats to nice rules of thumb (In fact I learned of a few just by preparing this answer!) LTD (long term depression) can occur in the hippocampus as well, and is dependent on the influx of calcium! As paradoxical as that seems, there is a negative feed back loop dependent on the levels of calcium ions inside the neuron, such that strong pre-synaptic stimuli create LTP (potentiation) and weaker (lower frequency) stimuli cause LTD (depression) and rare or intermittent stimuli cause no response. (see this and this for reference).
G-Protein coupled Receptors
G-Protein coupled Receptors are more of a general family of proteins than a specific example. They are metabotropic receptors (meaning they do not allow Ion's to flow through them). Rather when bound they release an G-Protein, which like calmodulin binds to other enzymes and activates them allowing them to do their job. They  can respond to many different neurotransmitters (or more generally ligands) and can do lots of different tasks depending on the  on what type of G-Protein it releases.
I'll give the muscarinic(M2) receptor for acetylcholine as an example. This receptor is found in the heart and responds to acetylcholine release from the Vagus nerve. When the GCPR binds to the acetylcholine it releases its G$\beta$ unit and it binds to potassium ion channels in the heart. This causes the outward flow of potassium ions thus lowering the voltage( hyper-polarizing the heart cell).
Furthermore G-coupled proteins can even induce changes in how many are present in the membrane (i.e. they are self regulating). These are produced by internal signaling cascades and are thought to be the reason for tolerance of drugs. Take for example the $\mu$-opioid receptor (activated by morphine, heroine and other similar compounds). These drugs will induce changes in how well the protein response to the morphine and if enough exposure then the cell will actually take the receptor back into the cell body and thus off the membrane in a process called endocytosis. (source here)
Literature reviews worth reading include (all open access):

Calcium signaling
NMDAR meditated LTP/LTD
GPCR's


If women need more dietary iron than men, then do blood donors also? My understanding that women's dietary iron requirements are slightly higher because I've heard the only way of losing iron from your body is by losing blood, and this happens in menstruation. This got me thinking if someone donates blood does their dietary requirement increase also?

Also, related to this, when a person gives blood we're told that our body remakes the blood we've lost, does this replenish the iron in the blood also, or is this "newly created blood" absent of the iron normally present in our blood?

This can indeed be an issue.  Frequent blood donors are known to get low on iron, which begins to result in fatigue, even before it starts resulting in low hemoglobin and anemia.

The cause is simple: like you pointed out, the loss of blood results in the loss of iron, and it takes the body a certain amount of time to rebuild the iron store.

As for your second question, the "newly created blood" will be low on iron until the body can absorb enough iron to replace that which has been donated.  Even on iron supplements, it can take up to half a year to rebuild the iron stores of the body to where they ought to be.

Sources:

Frequent blood donors risk iron deficiency, Miriam Shuchman, MD
Iron Deficiency & Anemia Treatment, Webmd.com


Does every mitochondrion in a cell contain the same DNA? I know that mitochondria of eukaryotes have their own DNA, more similar to that of bacteria than to the rest of the cell's DNA. I also know that a cell can have plenty of mitochondria, and I understand each of them has it's own DNA. Is it the same DNA?

I know that when a human is conceived, the mitochondria of the sperm are destroyed and don't contribute to the new cell. If there were no mutations and the process started with a cell with homogenous mDNA, that would mean that the mDNA not only within one cell but among all of the descendants was the same. But there are mutations because we have different mDNAs. Then shouldn't the mutations cause variety within single cells? It's hard for me to believe that there can even be a single human cell in the world that has homogenous mDNA because, if I understand correctly, an ovum retains many mitochondria during conception, not just one, so at least some of the variety within the ovum should be passed over to the conceived human. But perhaps it's extremely difficult for a cell with variously DNAed mitochondria to survive? Can it be estimated what the percentage of human cells with homogenous or nearly homogenous mDNA is across the world?

I'm asking this because I've heard that the mDNA can be considered another chromosome. I wonder if then every single piece of mitochondrial DNA should be considered another chromosome.

Please note that all I know about biology is what I learned in high school several years ago and the bits I know from Wikipedia and other internet sources. I would like to ask for possibly accessible answers.

EDIT: Reading up on this, I came across the term heteroplasmy. So it does happen that mitochondria of an organism can store different genetic information. But the article seems to suggest that it is an anomaly rather than the normal course of things. That seems strange to me. I understand of course that some mutations have to be harmful, but shouldn't some mutations and some kinds of in-cell variety turn out to be neutral or even advantageous?

I've also just read that a mitochondrion stores more than one copy of its DNA. That seems to allow for variation even within a single mitochondrion.

EDIT 2: I think it's possible that my question is unclear. There seem to be four levels on which mDNA variety can be considered: a species, an organism, a cell, a mitochondrion. I ask the answerers to focus on the third one. I will be happy to learn about the other levels too and I will consider such information on-topic, but my main question is about what happens in a cell.

This link seems to have good information that answers most of your questions.

In my mind, there are two types of mitochondria: ones that work and ones that don't. Mitochondria do have DNA but that mDNA is there to encode proteins for their specific functions (e.g. to create ATP). So, although the mDNA may not be uniform for every mitochondrion in your body, it is most likely functional unless you have a mitochondrial disease. If you do have a mitochondrial disease then it suggests that some of your mitochondria are functional and some are not (otherwise you would be inviable).

As discussed in the comments, all DNA undergoes mutations so that even identical mDNA genomes may vary after undergoing some mutations. It's possible that only one genetic line of mitochondria was passed to you from your mom. In this case all the mitochondria in your body would be identical (except for minor mutations). It's also possible that your mom inherited and passed on to you more than one genetic line (as is the case in viable mitochondrial disease).

Mitochondrial repair mechanisms do exist but they differ in various ways from nuclear DNA repair and may be more prone to damage.


Identifying type of inhibitor from $K_m$ and $V_{max}$ Apparently it is possible to identify whether an inhibitor is competitive or non-competitive from graphs of substrate concentration (x axis) and rate of reaction (y axis).

There needs to be a line for with inhibitor (constant concentration) and without inhibitor. The difference in $K_m$ and $V_{max}$ can then be interpreted to find out whether the inhibitor is competitive or not.

I know that if the effect of the inhibitor decreases with an increase in
substrate concentration then inhibitor is competitive.

However I don't understand how to tell from the graphs mentioned earlier and  $K_m$ and $V_{max}$. Could someone explain.

I have tried to google this but most of what comes up is scholarly articles which are beyond my level of understanding...

Competitive inhibitor competes for the active site. Therefore it will interfere with the binding of the substrate thereby increasing the apparent KM.

A strictly non-competitive inhibitor does not compete for the active site. It however inhibits the catalysis by reducing the available molecules of active enzyme, E0 (if it is a perfect inhibitor), thereby lowering the Vmax.

There can be mixed inhibitors too and there can be different kinds of mixed inhibition. For example an inhibitor that interferes with catalysis and can also compete for the active site.

Depending on how you define KM, a non-competitive inhibitor may or may not change it. If such inhibitor can bind to the enzyme at non-active site and reduce its kcat, it changes the KM as well as Vmax in case of Briggs-Haldane kinetics.


Why does breathing increase in higher temperatures? In my experiment, my group increased the temperature of a fish's water. We noticed the fish took more breaths than the prior normal temperature. Is this because the fish is trying to breathe in the water's oxygen, which is evaporating more quickly than in normal temperature?

As you can see on the diagram below, oxygen solubulity in water drops by increasing temperature, so your fish has to breath more to get the same amount of oxygen.

ref

You can find more info about why gas solubility is temperature dependent here:
Chemistry (Averill & Eldredge) / Effects of Temperature and Pressure on Solubility.


Do these things contain amylase? I have 10 samples of some food or other things and I need to know, if it contains amylase. I already ran an experiment with storch and iodine, but I have to make it right and my experiment must not be right.

List of samples:

Saliva (I know this one)
Banana peel (inner side)
Corn
Sponge biscuit
(http://www.kaloricketabulky.cz/fotografie-velka/f1136aba2e11082a/piskoty-detske-kulate.jpg)
Tomato
Banana (dried)
Bread
Potato peel
Ketchup
Milk

Thank you very much!

Amylase is an enzyme that breaks down starches to simpler sugars. Only living organisms can produce amylase. Animals produce only alpha-amylase. Plants, bacteria, and fungi produce both beta- and alpha- amylases. Like all proteins, the presence of amylase in food depends on if it is permanently denatured by high enough temperatures or extremes in pH. Interestingly, amylases can be classified into high/intermediate/low thermostability groups, depending on whether they become inactivated at a certain temperature. Taking this into consideration, saliva would definitely have alpha-amylase. Bread and biscuits may have alpha or beta amylase (depending on baking temperatures/pH, if amylase was added at all, and if it comes from a grain). Of the rest of your list, banana, corn, milk, and sweet potato would have amylase. Honey (not listed) would also have it. Tomato seems to amylase activity as well. For ketchup, it seems to be an added ingredient to speed processing.

Sources:

http://www.gmo-compass.org/eng/database/enzymes/80.amylase.html
http://www.lallemand.com/BakerYeastNA/eng/PDFs/LBU%20PDF%20FILES/2_7SOFT.PDF
http://www.ehow.com/info_12013063_plants-contain-amylase.html
http://www.ajofai.info/Abstract/Detection%20of%20amylase%20activity%20from%20vegetables%20and%20fruit%20in%20an%20undergraduate%20classroom.pdf


How can birds disperse seeds when they are able to digest them? I've just read in a book that birds' guts can digest almost all the consumed seeds with the exception of mistletoe and loranthus (which stays stuck on the branches). On the other hand, I know that the co-evolution with birds caused the enlarging of the fruits - for the fruit trees as an advantage in fast spreading.

But how do exactly birds spread the seeds they consume if they're digested in their guts?

Birds may indeed digest seeds under conditions of rest. It has been postulated that almost all current knowledge on mechanisms of internal seed dispersal has been obtained from experiments with resting animals.

A study with the mallard Anas platyrhynchos (common wild duck), claimed to be quantitatively one of the most important seed dispersing animals in aquatic habitats in the Northern Hemisphere, has shown that physical activity affects gut passage survival and retention time of ingested plant seeds. The authors fed seeds of nine common wetland plants to mallards trained to subsequently swim for six hours. They compared gut passage survival of seeds against a control treatment with resting mallards.

Intact gut passage of seeds increased significantly with mallard activity (up to 80% in the fastest swimming treatment compared to the control), and hence revealing reduced digestive efficiency due to increased metabolic rates. This enhances the dispersal potential of ingested seeds.

An extensive work-out after a meal generally slows down metabolism, as blood is redistributed to the musculature and away from the digestive tract.

These findings imply that seed dispersal potential by mallards calculated from other experiments with resting birds may be underestimated.

Reference
- Kleyheeg et al., Oikos (2015); 124(7): 899–907


Source of information on the evolution of aging/senescence Do you know a good review (published peer-reviewed or an online course or whatever) that offers a good overview of all hypothesis explaining the various patterns linked with aging?

I'd like this review to make the following things clear; antagonist pleiotropy, Gompertz and Weibull models and what theoretical explanations are underlying these models, mutation accumulation, reliability theory, eventually group selection, age-specific efficiency of natural selection, telomere length, the definition of senescence, and all not-cited hypothesis to explain the patterns of aging/senescence.

I don't know about just one source that fits everything you've asked, so here's a custom bibliography to get you started instead.

General Sources

I first learned about biogerontology from the excellent series of introductory essays at João Pedro de Magalhães' website, senescence.info; I definitely recommend starting here.

A short book written by two experts, for Scientific American Publishers, is Finch and Ricklefs' Aging: A Natural History. "The" book on the Evolutionary Theory of Aging is Michael Rose's Evolutionary Biology of Aging. "The" book on comparative biogerontology is Finch's Longevity, Senescence, and the Genome. A "pop" account of recent research (esp. to do with caloric restriction and long-lived mutants, which have people excited right now, and the search for longevity drugs) is David Stipp's The Youth Pill. A constantly-updated-with-new-editions-reference is The Handbook of the Biology of Aging. In 2008 (just missing the 2009 rapamycin excitement), Cold Spring Harbor Press published a collection on Molecular Biology of Aging. The Gerontological Society of America has an e-textbook out, that I think is going to be updated on the regular, called Molecular and Cellular Biology of Aging.

The Definition and Measurement of Aging

Usually, people define senescence as an increase in "mortality" with age. Mortality roughly means vulnerability; the older you are, the easier it is to die. Mortality is measured/estimated demographically, in terms of (hypothetical or actual) cohort survivorship. There are two quantities usually used: one for discrete-time, and one for continuous-time. Where $N_x$ the number of survivors still alive in a cohort at age $x$,

$q_x = \frac{{N_x}-{N_{x+1}}}{N_x}$ discrete-time; The Age-Specific Probability of Death.

$\mu_x = -\frac{N^{'}_{x}}{N_x}$ instantaneous; The Force of Mortality.

The first one is the fraction, of those alive at age $x$, who will die before age $x+1$. This estimates the probability that an individual aged $x$ will die before age $x+1$. This is intuitive: to age means that an 80-year-old is less likely to make it to 81, than a 20-year-old is to make it to 21. Notice that $q_x$ is bounded between 0 and 1.

The second one is the instantaneous rate of death, normalized against cohort size at that instant (whereas the first was the number of deaths in an interval, normalized against cohort size at the beginning of the interval). It is the instantaneous, age-specific, per-capita death rate. It can be visualized as the slope of the survivorship curve, divided by its height, times -1 to make it positive. It is not a probability. It has a dimension of rate ("per-second", "per-hour", etc) and it has no upper bound.

This way of defining senescence is described in Nature Scitable's Aging and its Demographic Measurement (although the authors give an erroneous definition of the force of mortality). It is discussed and justified intuitively, and at length, in Peter Medawar's The Definition and Measurement of Senescence.

Sometimes, you might want to count a decline in fecundity as aging, too, even if mortality wasn't changing. Or, you might want to define senescence in terms of various kinds of physiological performance. This is really a matter of taste, I suppose, or of what kinds of question you're trying to answer. Ageing or Senescence is just the part of getting older which, on top of having more birthdays, is somehow or other "bad" for you.

But the most common criterion is that $q_x$ or $\mu_x$ grows with age.

Mainstream Evolutionary Theory of Aging:

The mainstream idea is that aging evolves because of the declining force of natural selection with age. Natural selection "cares less" about things that happen late in life, than about things that happen early in life.

Mutation Accumulation (MA): the theory proposed in Peter Medawar's An Unsolved Problem of Biology. (Theory that aging is due to genes that are silent or neutral in early life, and deleterious in late life.)
Antagonistic Pleiotropy (AP): the theory proposed in George C. Williams' Pleiotropy, Natural Selection, and the Evolution of Senescence. (Theory that aging is due to genes that are beneficial in early life, and deleterious late in life.)
Disposable Soma: Proposed by Thomas Kirkwood and Robin Holliday; sometimes considered a version of AP. (Theory that aging is due to a tradeoff, in turn possibly due to allocation of limited resources, between reproduction and maintenance; selection favours less than perfect maintenance. Can be considered a version of AP where the "early beneficial effect" is increased maintenance, and the "late deleterious effect" is decreased survival.)

Summarized in Nature Scitable's The Evolution of Aging. Note that both MA and AP could be partly true; both kinds of genes could exist.

Both MA and AP are commonly cited as predicting that higher extrinsic mortality should lead to the evolution of earlier / faster senescence; but things may be more complicated than this.

The Declining Force of Natural Selection: Hamilton's Formalization

Medawar's and Williams' insights were verbal. William Hamilton did the math, and showed that certain formal indicators of the strength of selection on a genetic effect, necessarily declined with the age at which that effect occurs. These indicators were I think: 1) the partial derivative of $r$ (the intrinsic rate of increase / malthusian parameter, which he took to be fitness) with respect to the force of mortality at age $x$; and 2) the partial derivative of $r$ with respect to fecundity at age $x$. (The first starts declining at the age of first reproduction; the second starts declining immediately.)

In passing, this also demonstrated that a remark R. A. Fisher had previously made, and which Medawar had accepted, was fallacious. Fisher and Medawar had assumed that the strength of natural selection was proportional to age-specific reproductive value; but since reproductive value can increase with age, and Hamilton's indicators can't, reproductive value can't be measuring the sensitivity of $r$.

Hamilton's paper: The Moulding of Senescence by Natural Selection.
Charlesworth summarizes Hamilton's results and puts them in context in Fisher, Medawar, Hamilton and the Evolution of Aging.
Charlesworth's book Evolution in Age-Structured Populations is supposed to be quite important and to have furthered and refined stuff in this area.
Apparently things might be a bit more complicated than this? Baudisch has claimed that although Hamilton's indicators must decrease with age, other indicators, which aren't obviously unreasonable, can increase.

Gompertz, Weibull, and Gompertz-Makeham

The Gompertz equation is intended to describe how the Force of Mortality $\mu_x$ grows with age. The Gompertz equation was come up with empirically, not for any theoretical reason; it just seemed to Benjamin Gompertz to fit the data quite well, for a good stretch of adult lifespan. The same goes for the Weibull equation, as far as I know, and for the Gompertz-Makeham equation.

Gompertz is an exponential growth equation: $\mu_x = \mu_0 \cdot e^{Gx}$ (where $G$ is a parameter). It looks like a straight line when graphed on a semilog plot.
Weibull is a power growth equation: $\mu_x = A \cdot x^B$ (where $A$ and $B$ are parameters). It looks like a straight line when graphed on a log-log plot.
Gompertz-Makeham adds a constant to the Gompertz equation: $\mu_x = \mu_0 \cdot e^{Gx}+C$. This ruins the elegance of the semilog-graphing, alas; it doesn't look like a straight line.

Apparently some people have tried to show how eg. Gompertz can evolve in MA models, but the generality of this is questionable (see Box 2 in this Trends in Ecology and Evolution paper). Gavrilov and Gavrilova (proponents of the "reliability theory of aging", have said something about Gompertz and Weibull being special: ("Both the Gompertz and the Weibull failure laws have their fundamental explanation rooted in reliability theory... and are the only two theoretically possible limiting extreme value distributions for systems whose life spans are determined by the first failed component... In other words, as the system becomes more and more complex (contains more vital components, each being critical for survival), its life span distribution may asymptotically approach one of the only two theoretically possible limiting distributions—either Gompertz or Weibull (depending on the early kinetics of failure of system components).") I don't know what that means.

Gompertz is the most commonly cited / used equation, I think. It's supposed to be more accurate than Weibull. Gompertz-Makeham I guess is more accurate, but of course it would be - it has an extra adjustible parameter, which, if it isn't helping, you can just set to zero!

Sometimes these equations are erroneously presented in terms of $q_x$ instead of $\mu_x$. This is erroneous historically, but also because $q_x$ has an upper bound of 1 and couldn't possibly obey any of the equations, at least not indefinitely.

Sometimes people find it more intuitive to describe Gompertz' exponential growth in terms of how long it takes $\mu_x$ to double; in humans, this "Mortality Rate Doubling Time" is about eight years.

Note that the equation does not accurately describe early life; mortality often starts high in infants, before falling to its minimum, and then starting to grow again. Thus $\mu_0$ isn't the actual mortality rate at age 0, but the backwards-extrapolated mortality rate you would have had at age 0, if you were perfectly Gompertzian (or whatever).

It also may not describe very late life. A hot topic right now is "late-life mortality deceleration", where the exponential growth seems to slow down such that Gompertz overpredicts mortality in the very old; whether this is so, and why, is debated.

Reliability Theory and the Reliability Theory of Aging

"Reliability Theory" itself is just a mathematical framework for describing survival / failure rates and stuff. (Engineers use it to quantify stuff like, the rate at which parts have their first breakage, or whatever.) Some of the quantities it describes are basically the same as some analogous quantities in demography / life histories, if "first failure" is taken to mean death. For example, the "Survival Function" $S(t)$ is the probability, at time $0$, that failure will not yet have occurred by time $t$; this is obviously analogous to the probability $l_x$ that a newborn will still be alive at age $x$.

Systems can be made of parts; if you know the survival/reliability patterns of the parts, and how they go together, you can tell something about the survival/reliability of the whole system. To illustrate, compare two kinds of reliability structure:

A "series reliability structure" is one where, if any part fails, the system fails. An example would be a block held up by a chain; if any link breaks the block falls.
A "parallel reliability structure" is one where, if all parts fail, the system fails. An example would be a block held up by a number of individual rings, attached separately; only when the last ring breaks, does the block fall.

"The Reliability Theory of Aging and Longevity" is a specific theory proposed by Leonid Gavrilov and Natalia Gavrilova, intended to explain patterns of organismal failure ("death") in terms of component failure, and how the components are put together. If I recall, they propose that aging organisms are made up of redundant blocks of non-aging components; supposedly, this can explain near-Gompertzian aging over most of adult life, as well as apparent late-life mortality deceleration.

Group Selection

Heresy! Most evolutionary biologists / gerontologists, I assume, are happy with the mainstream theory and don't take the group selection theory seriously. Iunno, try Mitteldorf? Here's a paper and he also wrote a pop book with Dorion Sagan. On group selection in general as an explanation for altruism, I think David Sloan Wilson's the guy trying the hardest to defend it (or "a new version of it").

Molecular Mechanisms

Iunno, try The Hallmarks of Aging? The trouble is we really don't know what mechanisms cause aging. There's some good ideas, but finding evidence is haaaaard. One problem is that, if you want to know why some species live longer than others, and you're looking for physiological correlations, body size is a huge confound (elephants and whales live longer than mice and dogs), and so might be phylogeny.


How is it possible for only one in five children to have brown eyes when their parents both have brown eyes? I have observed that parents having brown eyes had three female offspring with blue eyes, one son with green eyes, while only the youngest daughter had brown eyes.

How can they produce so many blue-eyed offspring?

Possible...yes of course! The answer could stop there but I guess you want to ask how likely it is.

Here is a chart of probability of a given kid to have eyes of a certain color given the parents eyes color. (Note that the second column contain probabilites and not odds contrary to what the figure is stating).

The probability that $k$ kids out of $n$ have eyes of a color which appears with probability $p$ is given by the probability mass function of the binomial distribution $\binom{n}{k} p^k (1-p)^{n-k}$

Knowing that both parents have brown eyes (even for your oldest sister):

The probability that exactly one out of 5 offsprings have brown eyes (and the others have eyes of another color) is about 0.015 (3 out of 200).
The probability that exactly 3 offsprings have blue eyes (and the others have eyes of another color) is about 0.0021 (2 out of 1000)

You might want to calculate the probability of having $k$ or more kids that have eyes of a given color (a p.value) is obtained by summing probabilities. For example, the probability that 3 or more kids (out of 5) have blue eyes is  $\binom{5}{3} 0.0625^3 (1-0.0625)^{5-3} + \binom{5}{4} 0.0625^4 (1-0.0625)^{5-4} + \binom{5}{5}  0.0625^5  (1-0.0625)^{5-5} ≈ 0.0022$

Learn more about Stats

You'll probably want to learn a bit about statistics if some things are unclear. You might want to make sure you understand the concept of p.value and its interest and make sure you understand what a binomial distribution is. You may also want to understand the concept of multiple testing to avoid falling in simple pitfalls.


Regeneration capabilities in humans? To what extent can humans, (mammals in general), theoretically regenerate, and is their a way to speed up and/or exceed this original extent.

Regeneration - or actions perceived as regeneration by popular culture - depend highly on age and specific type of cells (epithelial tissue cells are a fine example). But you can't regenerate a leg-bone once removed.

But to get a more specific answer you to make a more specific question and define the terms you're using.


Difference between bacteria and bacteroids? During nodule formation Rhizobium is converted to bacteroids. What's the difference between them?

Bacteroids are the endosymbiotic forms of rhizobia (in the root nodules of leguminous plants).

Löhnis & Hansen (1921) J Agric Res 20: 543-556; emphasis mine:

  It is not superfluous to emphasize once more that persistence in
  calling these forms "bacteroids" is by no means to be recommended.
  They are true bacteria, not foreign bodies looking like bacteria, as
  Frank's pupil Brunchorst erroneously believed. To speak of a
  "bacteroid" growth of bacteria is no less absurd than it would be to
  speak of a "fungoid" growth of fungi.

https://naldc.nal.usda.gov/download/IND43966363/PDF

Gerson & Patel (1975) Appl Microbiol 30: 193-198; emphasis mine:

  Rhizobium is an aerobe, existing as a free-living bacterium in soil or
  as a partially anaerobic symbiont in the root nodules of leguminous
  plants. It is in the symbiotic form (bacteroid), which is frequently
  morphogenetically different, that nitrogen fixation takes place.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC365797/

MacKenzie et al. (1973) J Bacteriol. 113: 387-393; emphasis mine:

  [C]hanges [accompany] the transformation from the free-living rod
  forms to the nitrogen-fixing bacteroid forms. (...) During the
  transformation into the bacteroidal state the wall decreased in
  thickness, became less rigid, and developed a particulate surface.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC251641/


Light signals in the courtship and mating I am investigating on the emission of signals in the courtship and mating in the animals.

I know that the fireflies emit light signals as a courtship ritual.

Are there other animals that use this phenomenon of luminescence?

Many Ostracods (esp. the Cyprididae) use bioluminescence to attract mates. The Bermuda fireworm (a polychete worm) also uses bioluminescence to attract mates.

If you have not yet, you should definitely have a look at wikipedia > Bioluminescence


Why don't we breathe nitrogen when it makes up most of the air? Why don't we breathe nitrogen while it makes most of the air?

Why do we always tend to breathe oxygen, not hydrogen and nitrogen?

Animals use oxygen as a chemical energy source because oxygen gas can react with many other compounds to form oxides, which releases energy and happen spontaneously.

Both carbon and nitrogen can be made to react with oxygen, but otherwise they are pretty inert.  So of all the gasses in the air present at over a fraction of a percent, oxygen is the only one we can use for energy.

Hydrogen (and sulfer) are both possible substitutes for oxygen in the role of redox energy source, but are normally pretty small components of our environment.  On another planet they might well be the basis of biometabolism.

Of course the fact that plants can use carbon dioxide to fix carbon is a different case of biology using a gas out of the air.  Its the defining quality of plants!

The energetics of using CO2 is endothermic - it requires energy input. They have to use sunlight to get the energy to utilize this energy and its very costly energetically.  Animals can afford to move and grow because they use oxygen while they eat plants.


Evolution to store limited Fat Why are our bodies not evolved to store only limited amounts of fat, which won't kill us with all diseases associated with obesity?
Wouldn't obese people die faster and clean the gene pool for people who are slim?

"Wouldn't obese people die faster and clean the gene pool for people who are slim?"

If your hypothesis is right, the selection for such traits would only have begun in the last 20-30 years ("Worldwide obesity has more than doubled since 1980" http://www.who.int/mediacentre/factsheets/fs311/en/)

Natural selection wouldn't have had time to select against people showing tendency for obesity.

Also, obesity is a lifestyle choice, and not merely predictable by genetic disposition. I could be a "fit" person, but genetically predisposed to obesity.

Look up also genotype vs phenotype for further reading (http://evolution.berkeley.edu/evolibrary/article/genovspheno_01)


Movement in microvilli My textbook( COMPREHENSIVE TEXTBOOK OF PHYSIOLOGY VOL-1 by GK PAL) says:

  Microfilaments project into microvilli present on the epithelial surface such as on the intestinal mucosa, and extend up to the tip of microvilli. They help in microvilli movement.

How far is the second sentence correct? When I searched on Wikipedia( in a page about microvilli) I found following:

  As mentioned, microvilli are formed as cell extensions from the plasma membrane surface.Actin filaments, present in the cytosol, are most abundant near the cell surface. These filaments are thought to determine the shape and movement of the plasma membrane.

So does these two imply that there is some sort of movement (due to actin) in microvilli?

Just the presence of actin filaments does not mean a cellular structure that contains it would be dynamic. Moreover there are different types of actin filaments (filopodia, lamellipodia etc) and they have different dynamics.

Microvilli closely resemble filopodia; both these structures also share some regulatory and structural proteins (other than actin). However, there are some differences which makes filopodia highly dynamic in comparison to microvilli (Sebé-Pedrós et al., 2013; Sauvanet et al., 2016).

Microvilli, though not as dynamic as filopodia, are not static structures. They can grow and retract and there are regulatory mechanisms that govern these processes (Sauvanet et al., 2016).

  REGULATION AND DYNAMICS OF MICROVILLI AND MICROVILLAR COMPONENTS

  Microvilli on cultured cells are dynamic structures with three phases
  in their life cycle: (a) the generation of microvilli growing at 5
  nm/s, (b) a steady state of ∼5 min, and (c) a retraction phase with a
  rate of 1.2 nm/s (Gorelik et al. 2003). This leads to an average life
  cycle of 12.1 ± 5.6 min. The turnover of microvillar proteins has been
  recognized for a long time (Stidwill et al. 1984). The F-actin core in
  the microvilli of Caco-2 cells at steady state treadmills, with a rate
  of monomer addition at the barbed end of approximately 1.5–3.0
  s−1 (Loomis et al. 2003, Tyska & Mooseker 2002),
  corresponding to approximately 0.2 μm/min. The protocadherin
  intermicrovillar link stabilizes microvilli of intestinal epithelial
  cells, resulting in a prolonged steady state (Crawley et al. 2014).
  The actin filaments in the core of stereocilia treadmill more slowly,
  at 0.002–0.04 subunits s−1 (Rzadzinska et al. 2004) or
  hardly at all (Zhang et al. 2012).


How to tell if a given gene is a tumor suppressor or oncogene? This is a problem taken from "Concepts of Genetics", Klug et al, 10e. I'm given the following table about the mutations in the BRCA1 gene:
$$\begin{array}{c|c|c|c|c}
\text{Kindred}&\text{Codon}&\text{Nucleotide}&\text{Coding}&\text{Frequency in}\\
&&\text{change}&\text{effect}&\text{control chromosomes}\\
\hline
1&24&-11\text{ bp}&\text{Frameshift or splice}&0/180\\
2&1313&\text{C}\to\text{T}&\text{gln}\to\text{stop}&0/170\\
3&1756&\text{Extra C}&\text{Frameshift}&0/162\\
4&1775&\text{T}\to\text{G}&\text{met}\to\text{arg}&0/120\\
5&\text{N/A}&?&\text{Loss of transcript}&\text{N/A}\end{array}$$
Footnote: "*N/A indicates not applicable, as the regulatory gene is inferred, and the position has not been identified."

Using this information, how can I decide whether the gene is a tumor suppressor or an oncogene?

I already know that BRCA1 is a tumor suppressor, so put another way, how can I arrive at this conclusion given the data above?

I assume these are all carcinogenic mutations. Because some them are clearly recessive loss-of-function mutations (like loss of transcript), you can conclude that the function of the gene consists of "holding back cancer". When these mutations occur, they can generally be complemented by a healthy allele on the sister chromosome.

Oncogenes on the other hand, require gain-of-function mutations, like translocation to a more active promotor or dominant negative mutations (like a loss-of-function mutation in a protein which forms multimers, which get "polluted" by the mutant and thus can not be complemented by the other allele). In most cases this "increases" their stimulation of cell division and thus cancerous growth.

Loss of transcript of an oncogene would not cause cancer.


What does "radiographic progression" mean in cancer? I tried looking up the definition of the term "radiographic progression" using Google and medical dictionary, etc., but I couldn't find its meaning anywhere. All research articles that I found just use it, so I assume it is something common.

Please explain to me what "radiographic progression" means. I really appreciate it.

"Radiographic" refers to imaging modalities like x-rays, CT scans, MRI, etc.

"Progression" in medical terms is referring to progression of disease, where progression means advancing to the next stage, getting worse, etc.

Radiographic progression in the context of cancer would mean that based on X-rays, CT, MRI, etc, the cancer has gotten worse in some way. The exact meaning of progression has to be defined on some rating scale and will differ from study to study. Radiographic progression is not the only way to measure disease progression, other measures can also be used like symptoms experienced.


We know that the hepatitis C virus can live on surfaces for at least six weeks. Maybe longer. The infectivity study ended after just six weeks; why? Background

A paper has found that the hepatitis C virus (HCV) can remain infective for at least six weeks on ordinary household surfaces. You can see the free full text, or a summary for busy clinicians.

Elsewhere, Brian Krause has added:

"They tested their samples for (up to) 6 weeks.  At the time of the 6th week they still found infectious virus.  They did not test samples beyond 6 weeks, so they can't say anything about infection past that time."

My question

So, at six weeks, they saw that the virus was still infective. Why might they have ended the study right away instead of continuing it for a few more months?

They ran out of samples

Their test is destructive, they can't test the same sample twice. They planned out a number of samples to test for each time period and tested them. At the end of six weeks, they were done.

It doesn't really matter

The point of the paper is that HCV is infectious long-term on surfaces when not cleaned properly, indicating there is a risk of fomite transmission long after an infected patient leaves the area.

They also show that if surfaces are cleaned, the virus is killed effectively. The authors are not advocating to quarantine a hospital room until any residual HCV dies from air exposure, they are advocating being sure to appropriately clean hospital surfaces to prevent potential disease.

It isn't typical (in fact, it is impossible) for a single scientific study to answer all open questions in one shot. If someone wants to put an upper bound on the duration that HCV remains infectious in the world they can do a new study with longer time points.


Can both the overlapping genes (in opposite strands) produce proteins? I have recognized that both the forward and reverse transcripts from a genomic location code for protein products. Both do occur/express in the tissue of interest. In order to eliminate by chance probability, I have screened my entire list of genes and there are 6 different examples. I would appreciate if anyone having the knowledge about such exceptions could guide me further.

Is this phenomena of protein being coded from both directions (of a given genomic location) possible? Are there any known examples?

While overlapping antisense RNAs are quite well known, there are very few examples in which both the RNAs from the pair can code for proteins. However, it is not impossible. I can cite one validated example: RU2S (DCDC2) and RU2AS (KAAG1) pair.

While RU2S is constitutively and ubiquitously expressed, RU2AS is specifically expressed in kidney, bladder, liver, and testis. It is also expressed in certain tumours (Peltz and Dougherty, 1999).

 Peltz SW, Dougherty JP. Antisense Translates into Sense. The Journal of Experimental Medicine. 1999;190(12):1729-1732.


Solubility of Amylopectin and Glycogen in water The only difference between the structures of Amylopectin and Glycogen is that Glycogen is more highly branched than Amylopectin. How this difference between their structures makes difference between their solubilities in water?

The answer is relatively simple: Amylopectin is watersoluble, and this seems to be a classical textbook error, which has been propagated now for decades. As you say yourself, the only difference is the number of 1,6-glycosidic branches, which occur every 8-12 glucose monomers in glycogen and every 15-30 monomers in amylopectin.

There are even scientific articles which show that amylopectin is watersoluble, see the references below:

Green et al., Journal of Chemical Education vol 52, p.729 (1975) Which  Starch Fraction  is  Water-soluble,  Amylose  or
Amylopectin?
J. Robyt, Encyclopedia of Life Sciences (2001) “Polysaccharides: Energy Storage”


Why Is Most Life Symmetrical Externally But Not Internally? Mammals, reptiles, arachnids, insects, etc are all as far as I am aware symmetrical in appearance.

Take a human for instance, make a line from the top of our head right down the middle. However, internally it is not the same. Our organs excluding the kidneys, lungs, reproductive organs, etc are not symmetrically placed in our body.

Why do we not have an even number of each organ so it can be placed symmetrically?
If we have a single organ why is it not placed in the middle like the brain or bladder is for instance?
Is there some evolutionary advantage that led to this setup?

First, I think it worthwhile considering 'Why would internal symmetry be beneficial?' Developmental simplicity jumps to mind immediately. You can also consider relationship to external organs; the stomach and esophagus are lined up with the mouth which is symmetrical about the sagittal plane. Or maybe even balance; the lungs are large organs and if put to one side would likely cause locomotive issues. (Perhaps this is even an interesting topic for another question.)

That said, I feel, at it's core the evolutionary advantage which led to the lack of ubiquitous internal symmetry is space. Simply put, there is only so much room inside an organism and every little counts. Thus, if there isn't a need for a particular organ to be mirrored about a plane then there is a benefit in putting elsewhere: utilization of space.

I think a fantastic example of this is the human digestive tract. The key factor in the shape of the intestines is utilization of space, which directly affects the point at which is connects to the stomach, itself contributing to the asymmetrical shape of the stomach. One could envision other configurations, sure, and nature has. However, this configuration works quite well and the extraordinary use of limited space seems to outweigh all benefits of symmetry.

To directly respond to your questions above:

Question: Why do we not have an even number of each organ so it can be placed symmetrically?
Response: Each organ addresses (or addressed) a need of the organism. Addressing that need with multiple organs working in concert has benefits and consequences, as does addressing the need with a single organ alone. These benefits and consequences are balanced throughout the evolution of an organism.
Question: If we have a single organ why is it not placed in the middle like the brain or bladder is for instance?
Response: I feel space. Again, there are benefits to symmetry but there are many other factors at play. Some of which, it seems, are more important than symmetry at times.
Question: Is there some evolutionary advantage that led to this setup?
Response: I hope this has been addressed - I don't claim to have 'answered' anything, this is a question for discussion.

Other fuel for discussion:

In thinking through this question I found myself able to rationalize why internal symmetry isn't necessary. However, I'd be interested in seeing opinions on why, then, external symmetry is so prevalent.


Do all kind of unicellular asexual reproductions let mutations happen, resulting in evolution? I know about fission, an unicellular asexual reproduction method, where the mother cell splits into two daughter cells. Does this kind of asexual reproductions let mutations happen, leading to much needed evolutionary process? Is it same for all unicellular asexual reproductions?

It is not essentially asexual reproduction that causes mutations. Mutations can be caused because of errors in DNA replication which can happen during both mitosis and meiosis.

Mutations can also be caused because of error-prone DNA repair mechanism.

Other than these intrinsic factors there are physical and chemical mutagens that alter the DNA or accelerate the intrinsic mutagenesis mechanisms.

These mechanisms are universally common for all living organisms (that we know of :P ), however, their tolerance to mutagens and rates of intrinsic mutagenesis may vary.

Have a look at this post too.


About what percent of mutations are not adaptive? Many popular texts that discuss evolution and natural selection often mention that many (or most) mutations are bad (not adaptive).

Have there been any studies on what the rough percentages are? (E.g. Is it 90%? 99%? 99.9%? If this number varies by species, an answer could just focus on one particular species.)

As suggested by the McGrew comment, this is dramatically dependent on the shape of the fitness landscape. It will vary quite a bit from situation to situation.
More precisely, you are interested in the distribution of fitness effects (DFE) of mutations, and the upper tail specifically.
Wikipedia has a section on this. In there, they note one study of a virus that suggests that ~4% of mutations are beneficial. That may be an overestimate, and many of those are probably only very slightly beneficial. Probably the number is lower in non-viral organisms.
For a review on the DFE of new mutations, see here. They write in their section "Advantageous mutations":

As expected, relatively few of the mutations that are not
effectively neutral are advantageous.In three mutagenesis
experiments, the proportion of advantageous mutations was 4% in the RNA virus vesicular stomatitis virus (VSV)15 (FIG. 1), 0% in Escherichia coli(14), 0–15% in the bacteriophage φX174 (REF. 40), 0% in φ6 (REF. 13) and 6% in Saccharomyces cerevisiae (16).


Is a haploid essentially half of a homologous pair? Is a haploid essentially half of a homologous pair? I understand that a haploid consists of only one set of each chromosome, so does that mean that if that chromosome was replicated the cell would become diploid and have homologous pairs?

Yes, you seem to have understood it correctly. On top of haploid and diploids, there are also cases of triploids, hexaploids, octoploids and others.

For example, some species of strawberries are decaploid (10 copies) (Hummer 2012). Then, there are the extremes. In Entamoeba populations, there can be variation in ploidy level among individuals ranging from diploid (2 copies) to tetracontaploid (40 copies) (Mukherjee et al. 2008)!


What do phagocytes secrete? What do phagocytes release after interacting with a pathogen? I know that this is a broad topic but I only need a general and concise answer.

I think it would be hard to delineate what secretions are specifically because of phagocytosis, because in that sort of environment you have multiple types of cells secreting things, and multiple signals through such pathways as toll-like receptors (TLRs). So, I looked at papers involving activated professional phagocytes such as macrophages and neutrophils. The secretome of the activated cells follows a somewhat typical pattern for innate immune cells: IL-1ß, TNF family, interferons, IL-6, IL-8, and a host of other chemokines and cytokines (1, 2, 3). Mast cells of course secrete things such as histamine in response to Fc-receptor stimulation and TLR signaling.

Non-professional phagocytes like epithelial cells lack receptors to make phagocytosis efficient, but I'm far less certain about the body of data on non-professional phagocytosis. We know that activated epithelium and endothelium secrete inflammatory signals to attract immune cells, for example, like IP-10 which attracts CXCR3-expressing cells.


Why does so much variation exist within species? My last phrasing of this question did not go down well, so I will try again.

The genotype of species is not always the same. If you ask yourself why not all of these possible expressions except one have died out, a natural answer is each genotype occupies a specific niche: For example, different eye colors might be found attractive by different kinds of people. If the the genotype for one eye color became more rare for some reason, other individuals with this genotype had a higher mating chance; the frequency of that genotype would get pushed back up.

But there seem to be genotypes (for example, having zits) that don't occupy any niche at all. Why didn't they die out?

First of all, your assumption is incorrect: those are not genotypes and they do not occupy specific niches. You are talking about phenotypes (eye colour) or in the case of acne, not a trait at all.

I'll answer the question I think you're asking: why does biological variation exist?

Variation is constantly being generated by mutation, errors in the replication of the genome of an individual. If a mutation occurs in the gametic cells, it affects the genotype of the offspring. By affecting the genotype, it may or may not have a discernable effect on the phenotype. Where a gametic mutation isn't fatal, it has a chance of becoming established in the population when that mutant individual breeds. That chance is increased the further along the gradient from harmful to beneficial that effect of that mutation is.

Variation also exists because development responds to environmental factors, not just genetics. Different individuals grow in different environments, and have unique combinations of factors influencing many traits.

The reason variation persists is because, except under conditions of extreme selective pressure or genetic bottlenecks, many traits have no impact on survival or fecundity (reproductive success) or are determined only partly by genetics. Height, for example, only has a very slight impact on fecundity within quite a broad range of heights. It is partly genetically determined, and partly determined by environmental factors such as diet (Eckhardt et al. 2005), exposure to toxins during development, muscular development etc.

If height were the key factor in human mate selection, we might see a gradual reduction in the range of heights, and a gradual increase in average height. However, what we see in reality is that height has changed through human history in concordance with economic factors like social status, inflation and war (e.g. Steckel, 2001), suggesting that nutrition is a major determinant.

I know it wasn't your choice of example, but for more detail on the effects of natural selection on human height, see this question.


What does it exactly mean to sequence the genome of a species? Since all organisms are different from each other - that is, we all have different alleles, some SNP, microsatellites, etc. -, what does it exactly mean, for the genome of a species, to be sequenced? I understand what it means for an organism's genome to be sequenced, but I don't really get what it means for a species.

I'm quite confused about this. Thanks in advance for the help!

Sequencing a "species" builds a reference genome that is considered to be a good "representative" of the species. Of course there will be genetic variation between the reference and healthy specimens in practice (usually SNPs), however it should be minimal.


What insect is this, large swarms? I live in Brisbane, Australia and these creatures arrived a few weeks ago for a day or so and then they disappeared. There were thousands of them. I would love to know what they are.

That is some sort of ant. Many species of ants have this huge "nuptial" flights, particularly after rains, where winged males and females leave the nest in swarms. Males die shortly after, while females lose their wings and start a new nest in the soil. I'm not familiar with Australian species, but the fact thatyou can see a "waist" shows you that those are winged ants.


Sleeping Pill Overdose How does an overdose of sleeping pills kill?
What are the body's reactions to an overdose?
In an article published in ScienceDaily, I read that "Sleeping pills owe half their benefit to the placebo effect".
So what constituents of a sleeping pill, when taken in excess, lead to a negative reaction?

Some hypnotics — the active component of sleeping medications — act as central nervous system (CNS) depressants, which in turn depress breathing or respiration, especially when mixed with other drugs, such as alcohol.

If your breathing slows sufficiently and is arrested, as can be caused by an overdose of CNS depressants, your vital organs will be starved for oxygen, which in turn can lead to brain damage and — ultimately — death.


What order does this bug belong to? I caught this insect in my house.
It has 6 legs, long antennae, 2 pairs of wings and is dark brown.


Is scratching in humans vestigal? Scratching and biting helps furred animals dispose parasite insects from their surface. Is it a productive action for humans who have less fur, have hands that can pinch off parasites and can help each other out?

If evolution were perfect, humans would never scratch, and to resort to pinching off any actual parasites - scratching and biting could break skin and expose it to germs.

Humans usually scratch to stop itches. Because scratches are a more high-priority sensation than the itch, the nerves stop transmitting the itch signals to your brain for a while.


Gluconeogenesis in the liver Glycolysis yields 2 net ATPs. However, gluconeogenesis (lactate->pyruvate->glucose) costs 6 ATP, with a total net loss of 4 ATP.

Does the body not care about the net loss because of the potential energy from glucose to yield up to 38 ATP?

The brain and also the erythrocytes need glucose to survive.
Gluconeogenesis is one of the possibilities of the body to keep the glucose levels stable and to avoid hypoglycemia. The precursors needed come from amino acid and lipid metabolism, and is turned on, when the body has no energy sources available which can release glucose, like carbohydrates in the food or the degradation of glycogen.

As you said, it comes at a price, making glucose itself costs a lot of energy. This process is available to maintain the level of glucose, which shows the importance of it.


Will an 11W UVC lamp kill bacteria? If I shone a UVC lamp (11W) on something (say for example a plastic phone case) for an hour, would that kill off a noticeable amount of bacteria? That is, if I were to go over the case with a cotton swab before the hour and swipe the cotton swab over a petri dish with nutrients and if I were to do the same after the hour with a different cotton swab and a different petri dish. Do you think that after a week there would be a noticeable difference in bacterial growth between the dishes? I think it should, since some filters for ponds work the same way, but I'm not sure, since in my case, the light needs to penetrate about 10 inches of air first and the environment isn't as closed off. What are your ideas on this?

Some physical methods of sterilisation are in hospitals

Steam autoclaving
Dry heat – thermostat
White light / UV light sterilization

where continuous UV light has poor penetration.
UV radiation heat is absorbed by proteins and nucleic acid.
All micro-organisms contain tehm.
They inactivate the DNA.
There will be electronic and photochemical reactions by

photolysis
loss of colony-forming ability
enzyme inactivation
destruction of nucleic acid.

  If I shone a UVC lamp (11W) on something (say for example a plastic
  phone case) for an hour, would that kill off a noticeable amount of
  bacteria?

Direct answer: Not all bacteria, but some.
UV light has poor penetration so it will not expose all bacteria.
Most prevalent bacteria there

streptococci,
staphylococci and
some others.

I estimate that the majority of the bacteria will remain because the light cannot reach each corner of the object.
In clinics, many hours and high temperatures are used to kill bacteria.
UV light is not efficient there.
I think the problem is that you cannot reach each corner of the object.
The high temperature and disinfectants can then again reach the clinical instruments throughly.
Manual work is however still needed.

You can then take examples of bacteria.
Search their corresponding temperature ranges.
The survival can also be dependent on the nature of the light of the bulb.
Each bacteria has an individual structure.
We can manipulate the environment to make bacteria more vulnerable to the heating i.e. to change the structure of the bacteria.
We can increase the duration of the heat exposure to make kill of the bacteria more effective.


Which human body hormonal systems exhibit 24 hour diurnal cyclical activity? I'm researching the possible connection between the dream content and the activity of various organ or hormonal systems within the human body. I'm looking for information on biological cycles within the human body that occur on a 24 hour cycle and may influence the sleep cycle, dream content or the overall state of awareness.

So far I was able to find:
Adrenaline, cortisol, testesterone - circadian endogenous cycle.

leptin, glucose, insuline  -  peak with awakening, decline with bedtime

What else within the human body is functioning on a predictable 24 hour cycle?

Thank you for any information!

The real answer is probably more than you want, but its easy to do better than the list above.

I took a look through GEO for human circadian expression data and surprisingly I only found 2.

Looking at GSE2703 - the rhesus circadian expression experiment, they have shown 355 genes that are rhythmically expressed.  This is not a great experiment because they only looked over a single 24 hour period.  Its only the adrenal gland.  Nonetheless they found 355 genes which seemed to be circadian.  the table is supplemental data to the article,  listed below.

I see a fibroblast growth factor receptor, some hydrocarbon nuclear receptor components, sterol regulatory factors, bone morphogenic protein 2, glutamate receptor, thrombonspondin receptor, ryanodine receptor 3 (what is that?) , lysophosphatidic acid G-protein-coupled receptor 2, purinergic receptor P2Y, G-protein coupled.  You might find more if you know what you are looking for.

The other circadian study was on human muscle, which will no doubt give different answers.  I imagine circadian behavior is highly tissue dependent.

Reference: Lemos DR, Downs JL, Urbanski HF. Twenty-four-hour rhythmic gene expression in the rhesus macaque adrenal gland. Mol Endocrinol 2006 May;20(5):1164-76


Why do we add salt when precipitating DNA? All the DNA extraction protocols I have seen involve adding salts to the extraction buffer. What is the purpose of the salts? What happens if they aren't included?

The role of the salt is to neutralize the charge of the DNA's sugar phosphate backbone.  This makes the DNA less hydrophilic (less soluble in water).

Ethanol has a lower dielectric constant than water so it's used to promote ionic bonds between the Na+ (from the salt) and the PO3- (from the DNA backbone) causing the DNA to precipitate.


Is this pCAMBIA co-transformation possible? I would like to know whether the pCAMBIA1200 and pCAMBIA0380 be used for co-transformation of rice using Agrobacterium LBA4404.They probably have the same ori site so they belong to the same incompatibility group.So will they co-exist in one Agrobacterium strain and be transferred to the rice plant?

Please let me know.

Please check and tell me and how do I go about the co-transformation of rice using Agrobacterium starting from E.coli


What does the term 'glycogen mobilisation' mean? I read that glycogen is a mobilised store of glucose:

Glycogen is a readily mobilized storage form of glucose. It is a very large, branched polymer of glucose residues (Figure 21.1) that can be broken down to yield glucose molecules when energy is needed. Most of the glucose residues in glycogen are linked by α-1,4-glycosidic bonds. [Source]

When looking online, mobilisation refers to something that is capable of movement.
I think glycogen mobilisation has something to do with glycogenolysis but not sure how to easily define glycogen mobilisation.
How would you define glycogen mobilisation in the easiest definition?

I think the key to understanding mobilization in this context is in the second sentence:

[Glycogen] can be broken down to yield glucose molecules when energy is needed.

The authors are using mobilize in a figurative sense to suggest that glycogen can be quickly and efficiently metabolized to suit the energy needs of the body, like an army may be mobilized to fight a war.  See definition #2 on Wiktionary:

mobilize (verb)
2. (transitive) To assemble troops and their equipment in a coordinated fashion so as to be ready for war.


Neurons competing for survival I was reading in a book that in the process of neurogenesis - when new neurons are born -  neurons compete for survival. Or in other words they have to make themselves useful to the brain otherwise they die and become processed as brain food.

To what extent is this real and how often does this happen?

i think that in the book I was reading it the author mentions it happening in early life, but I'm not entirely sure.

Would be great to know.

Thank you!

It's definitely real ;)

Depending on your previous knowledge, this review from 1987 might be a good starting point.
http://science.sciencemag.org/content/237/4819/1154.long

To give you an idea of recent developments this article is an easy read. Be sure to browse the references.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612357/


What is this bird of prey with white belly? This bird was around the house in northern Switzerland (alt: ~700 m) on January 17th 2016, and I am just wondering what kind of species it is.

The legs are yellow and the under (I do not have picture while flying, but saw it just before) is almost all white with just a black (or dark) stripe on the end of the tail.

For me it looks like a nordic species of Buteo buteo but can any specialist confirm it?

I think your identification is correct - this is a juvenile Common buzzard (Buteo buteo), which have a lighter coat than the grown-up birds. See this image (from here), which also shows a juvenile bird:


How are at home fermentations without starter cultures controlled? When making fermented food at home, particularly those that are made without the addition of a starter culture, how does one ensure that the correct types of bacteria are carrying out the fermentation? Is this generally due to the properties of the food that is fermented?

A "starter culture" is just a culture of preferred organisms. They probably differ little from local wild organisms. For example, a mixture of flour and water left to stand will (with luck) be colonized by yeast in the air that result in a serviceable yeast culture. Control of this process entails nothing more than observation over time. The environment and nature of the medium suffice to control the bugs that colonize it.

Both the Korean and Chinese versions of kimchee depend on moisture and acidity (and perhaps salinity) to inhibit unwanted molds/bacteria. The process is evidently self-controlled, but I recall seeing a film in which it was said that failure to add salt to the mixture could result in spoilage. Note that in the linked article, the author says cavalierly that one can scrape any mold that forms off the cabbage and continue with the fermentation because mold will not grow in liquid--patently false but probably "true enough" not to affect results.

Aspergillus oryzae colonizes rice, and rice with Aspergillus growth can be subjected to a secondary yeast fermentation that yields sake. The commercial production uses highly-prized starter cultures for both the mold and yeast, but it is possible to substitute other varieties of Aspergillus. For example, one can induce A. niger to grow on a citrus peel, and transfer the colony to rice. The sake that results is fine. But in this case one would want to rule out species of Aspergillus that are associated with toxins. For similar reasons some care is taken in sterilizing containers used to make wine.

In any of these processes there is a possibility of colonization by the wrong flora. The cultures are controlled by the content of the nutrients and climate and observed carefully. Over centuries there have probably been many unfortunate accidents involving unwanted organisms. There is nothing like violent illness to bring the integrity of a process into focus.

In short, the control of home fermentations lies in (1) statistical likelihood that the right organism is present in the environment; (2) the nature of the nutrient and climate; (3) the experience of the person(s) monitoring the process; and (4) luck.


If higher levels of atmospheric oxygen can lead to larger animals, can it also lead to larger plants? According to some information, in the ancient past (at least some) animals grew larger due to a higher levels of oxygen in the atmosphere. So for example there is this study regarding dragonflies.

Can higher levels of atmospheric oxygen also lead to larger plants? For example, would it be possible to grow gigantic strawberries in a hermetically sealed greenhouse that maintains a higher atmospheric oxygen concentration?

Oxygen is good for animals because our basic metabolism is this:

  High energy carbon molecules + O2 → energy + H2O + CO2

Plants do that too at night, but during the day, they mostly do this:

  High energy photons + H2O + CO2 → High energy carbon molecules + O2

Rubisco, one of the most important enzymes in photosynthesis, can bind to O2, leading to less efficient photorespiration, instead of photosyntheis.  Rubisco is often a bottleneck in photosynthesis, in large part for that reason.  So high oxygen isn't helpful to plants.  In fact, C4 plants and CAM plants have evolved more complicated physiology to minimize the effect of O2.


Is my Y-chromosome the same at 78 as it was at 18? How accurate is a Y-dna test at age 78?

By and large, yes.  Some telomeres might be shorter, but the rest of the sequence will not change.  Certainly, any regions used for ancestry testing will be stable.


How high into the air are spores of molds commonly occurring? I understand so far that most of the air surrounding us contains mold spores so that given the right environment and a food source they start to grow. I assume this is true for air close to the earth. But how high mold spores are still common?

To clarify: I don't want to grow mold, I want to know how high into the air on earth mold spores are usually common.

Air currents can carry bacteria and mold spores into stratospheric altitudes.  Early balloon collections found bacteria and mold in air samples at a little above 71 thousand feet altitude.  There were only a few colonies, but we also know that our bacterial media often do not allow many microorganisms to grow.

More recent studies of the atmospheric microbiome have indicated that a wide variety of bacteria and fungi can routinely be found in the atmosphere thousands of feet up.  Modern measurements find about 10 million living microbes per cubic meter.

Sandstorms or jet streams are known to be able to move living bacteria long distances.  Spores are often of about the same size and I see no reason why we will not find that they do the same.


What is the name of this snake? This baby snake just came inside my house in Sri Lanka, and I'm wondering whether it is venomous. Do you know this snake?

I am posting this from my phone so I am unable to format properly. And I have small children in my house, therefore I am worried about their safety.

Size: < 30 cm (I think it was a baby snake).

Location: Sri Lanka (in southern Asia)

We live in an urban area without any rivers near by.

I'm not an expert by any means, and anyone with proper training could probably provide a more informed opinion, but here's my thoughts. The patterning looks similar to Oligodon taeniolatus, an small, nonvenomous snake found throughout the region:

I'm not entirely sure about this identification, mostly because the pattern on the head looks a bit different. Sri Lanka has a large diversity of snakes and finding an definitive identification might be difficult without better images. There seems to be only a handful of snakes considered deadly, and this doesn't appear to be one of them. However, as I said, I'm not an expert, and even if it's not one of the 'deadly' ones, that doesn't mean it couldn't be dangerous to small children or pets. If you intend to capture and release the snake away from the house, I'd still recommend caution when handling it or contacting a professional.


Evolution of diversity and extinction resistance I saw a comment on an answer to another question that touched on an interesting topic:

  keeping diversity is useful for parameter exploration or to adapt to future environmental change

My initial thought was that evolution doesn't "know" about the future, so natural selection might decrease genetic diversity even if it meant dooming the species in the long term.

On the other hand, species that have low genetic diversity may be more likely to go extinct eventually.  So perhaps over time the surviving taxa are those that have evolved mechanims to "hedge their bets" against future environmental changes.

It's clear that some of the parameters that affect genetic diversity within a species (e.g. mate selection, mutation rate) are heritable, but it's unclear to me how the short-term processes of natural selection relate to the extremely long-term processes of speciation and extinction.  This gets into some of the same issues as group selection — how can natural selection, acting on individuals, lead to traits that benefit entire populations or clades?  (Perhaps this simply cannot happen.)

Has any work been done on the topic of extinction resistance or the evolution of mechanisms to create and preserve diversity within populations or taxa?

This is a big question so I don't expect a full answer here.  I'm just looking for some references as a starting point to learn more about this topic.

The topic you describe is very interesting and known as "species selection." Some traits exist that not only affect the reproductive success of individuals, but also affect the diversification rate of the entire species, either through affecting the extinction rate, the speciation rate, or both.

To give you an example, I'll summarize this paper by Goldberg et al 2010. Self-incompatibility (SI) in plants is the ability of a plant to reject its own pollen to prevent inbreeding. This mechanism is expected to increase the genetic diversity of the plant's offspring. Self-incompatibility has been lost many times in the history of flowering plants, yielding self-compatibility (SC), which allows a plant to breed with itself. A plant that can breed with itself has an advantage in that even if the population size is low and it can't 'find' another individual to breed with, it can still breed with itself to produce offspring. However, this trait is expected to result in decreased genetic diversity in the offspring due to inbreeding.

The transition from SI to SC is a common transition that cannot easily be reversed. One might expect, then, that SI would be very uncommon as lineages would lose it to SC. However, it turns out that SC lineages have a lower diversification rate than SI plants in the Solanaceae due to the fact that SC lineages have a higher extinction rate than speciation rate. This difference in diversification allows SI to persist. This is an example of trait-dependent net diversification rate. It is not known exactly why SI lineages have a higher net diversification rate, but it could be related to the higher effective population size which results in "increased polymorphism,
lower linkage disequilibrium, more
efficient response to purifying selection, more
extensive geographic distribution of genetic diversity,
and lower rates of extinction".

If you want to read more, I can suggest a few more papers:

The Units of Selection by R.C. Lewontin

Darwainism and the Expansion of Evolutionary Theory by S.J. Gould

Species Selection: Theory and Data by D. Jablonski


Evolution of Homo Erectus to Homo Sapiens I just read an article on Wikipedia and noticed that some similarities between Homo Erectus and Homo Sapiens in the "Comparative table of Homo species". My question is;

Is it possible to say that some members of Homo Erectus species
have survived up to now and they are living in modern world as members
of Homo Sapiens?

It is not plausible that members of Homo erectus would survive and remain a separate species from Homo sapiens. For members of Homo erectus to survive implies that there wasn't significant interbreeding with Homo sapiens, which would require a significant population of Homo erectus.

There is some evidence that Homo erectus and other hominids interbred with Homo sapiens. So it is more likely that there may be some people with more genetic traits from Homo erectus than others. However, by significant interbreeding, there currently only exists a single species that may contain ancestors from multiple hominid species.


Can erythrocytes Function without plasma? my title is not very specific. So i will proceed to clarify it.
I am trying to make sure that the only blood cells in a sample are Erytocytes, since i want to evaluate their metabolism, I am aware that they don't have Mithocondria and thus catabolize Glucose into Lactate, (I belive I am not making false statements, however if any corrections pop up please give me a heads up.)
Thus a way I thought of getting rid of leucocytes was through centrifugation, erythrocytes would be at the bottom of the flask and if We got rid of Supernadant (plama and fine layer of leucocytes), we would have a much purer sample of erythrocytes.

My question is: Do they stil carry out their metabolism, so i can a posteriori evaluate it, even after centrifugation and gettting rid of the plasma. Or evaluating the lactate production afterwards would be impossible? I know there are more easier and methodic ways of getting rid of leucocytes(irradiation that destroys all nucleated cells and leucoreduction by filtracion, for example), but this is somewhat hypothetical, and i need to know the final answer in these circumstances.

Thanks in advance :)

Erythrocytes need more than just glucose in order to function and, they also need a extracelullar medium who shares the same osmolarity, so placing your red blood cells into a medium that solely has glucose will be problematic. If you solely want to evaluate the lactic fermentation carried out by erythrocytes on a short period of time, then you can add the blood plasm on your centrifuge tube (which will be in the superior layer) to the newly separated erythrocyte fraction. This way, we make sure your extracelullar medium not only has every metabolite needed, but is also isotonic with respect to your erythrocytes. If you're planning on evaluating this pathway for a considerable amount of time (days, perhaps), then you, most likely, will have to prepare a solution with glucose that is isotonic with respect to your red blood cells.


How are the boundaries of a gene determined? What statistical processes and methods are used by geneticists/molecular biologists to know where one gene starts and one ends?

I know of only one naive approach to determining the boundaries of a gene : RACE-PCR. There are two kinds, 3' and 5' RACE, which allow to find the respective extremities.

The rationale is the following :

You perform a reverse transcription of the transcript of interest using a specific primer. At this step you have a specific single stranded cDNA.
Then you add a stretch of identical nucleotides called the homopolymeric tail in 5' of the cDNA.
Finally you perform a PCR using one specific primer and one universal primer that recognizes the homopolymeric tail. You can sequence your amplified cDNA and find where it is located in the genome with a 1 bp resolution.

For the 3'RACE, the concept is the same but the poly-A tail is used instead of generating it yourself with the terminal transferase.

See this paper for a detailed protocol :

 Sambrook J, Russell DW. 2006. Rapid Amplification of 5’ cDNA Ends (5'-RACE). CSH protocols 2006.

Also, the corresponding wikipedia article gives you more details about what is happening at each step, but beware, there is an error : it is said that for the 5'RACE, the terminal transferase appends the homopolymeric tail in 3' while it appends it in 5'


How to identify the GPD gene when the sequence varies between organisms? I'm reading a paper on genetic transformation of a fungi and the plasmid used in the paper uses two forms of the same GPD (glyceraldehyde3-phosphate dehydrogenase) promoter to drive a GFP gene, one from Agaricus bisporus and one from Lentinula edodes (GenBank: GQ457137.1).
However, I noticed that the sequences for the aforementioned GPD promoters do not match the reference sequence in GenBank (NC_007251.2) which itself is derived from another organism.
Why are there different sequences for the same promoter? Furthermore, how would I identify the GPD gene in another organism if I'm unable to compare it to a known sequence?
The organism I wish to transform has had it's complete genome sequenced and my transformation would be much more effective if I could use a native promoter like GPD.

I might be misunderstanding you here, but I take from your links above that you want to match the GPD promoter regions from two (distantly related) fungi Agaricus bisporus and Lentinula edodes, to the GPD promoter of Leishmania major, which belongs to a completely different Kingdom!
Promoter regions tend to be relatively poorly conserved between species compared with protein coding regions, even for closely related species. Given the evolutionary distance between the species you are mentioning, the chance you will find any homology between their promoter regions is probably zero.

Furthermore, how would I identify the GPD gene in another organism if I'm unable to compare it to a known sequence?

What I would do is to take the translated GPD protein sequence, which for Lentinula edodes would be GenBank BAA83550.1. I would then use that to search for protein matches using blastp, specifically subsetting for Leishmania major; and use the result to locate the coding gene in the genome. You can also do this in one single step with tblastn, which looks for matches in a translated nucleotide database (see this tblastn example query).
You can then simply take the 1000 bp or so upstream of the coding region to represent your GPD promoter.


Confused about the calculation of BLOSUM matrix I am trying to understand how the BLOSUM matrix is calculated.

I found a very nice tutorial here: http://www.cs.columbia.edu/4761/assignments/assignment1/reference1.pdf

Also i read through the wikipedia article, and a book "Understanding bioinformatics" from Marketa Zvelebim and Jeremy O. Baum

After i thought i understand the method i tried myself with this "alignment" (i will refer to the variable as they are at the link i provided)

Q
Q
S

So it has only one column, and 2 type of amino acids.

The Count pair frequencies (C) for Q -> Q substitution is 1 (2*1/2) and for Q -> S it should be 2 (2*1).

To normalise it T = 3 as 3*2/2

The q values then seem to be q(Q->Q) = 1/3, q(Q->S) = 2/3

The p(Q) is then 1/3 + 2/3/2 = 4/6

p(S) is 2/3+1/3/2 = 2/6

The e(Q->Q) = (4/6)^2 = 4/9

e(Q->S) = 4/6*2/6*2 = 4/9

Thus

S(Q->Q) = round(log2((1/3)/(4/9)) = -1

S(Q->S) = round(log2((2/3)/(4/9)) = 1

So from this alignment it is more likely to substitute a Q to an S rather then Q to Q? This makes no sense for me.

What am i missing?

Ok I'll try to go through it myself and see what happens.

First, we get the pair counts: $$ c_{ij}=\begin{cases} \displaystyle\binom{n_i}{2} & i=j\\ n_i n_j & i\ne j \end{cases} \;\;\;\;\;\implies\;\;\;\;\; c_{11}=1, c_{12}=2, c_{22}=0 $$ Clearly, the normalizer is just $T=\sum_{i\geq j} c_{ij}=3$ and $c_{ij}\equiv c_{ij}^{(1)}$ since there's only one column. Then our pair distribution is: $$ q_{ij} = \frac{c_{ij}}{T} \;\;\;\;\;\implies\;\;\;\;\; q_{11}=\frac{1}{3},\;q_{12}=\frac{2}{3},\; q_{22}= 0  $$
Hence, the occurrence probability per residue: $$ p_i = q_{ii} + \sum_{i\ne j} \frac{q_{ij}}{2} \;\;\;\;\;\implies\;\;\;\;\; p_1 = \frac{2}{3},\;p_2=\frac{1}{3} $$
and the expected pair frequency:
$$ e_{ij} = \begin{cases} p_i^2 & i=j\\ 2p_ip_j & i\ne j \end{cases}\;\;\;\;\;\implies\;\;\;\;\; e_{11}=e_{12}=\frac{4}{9},\; e_{22}=\frac{1}{9} $$
Now we can finally compute the odds ratios:
$$ r_{ij} = \frac{q_{ij}}{e_{ij}} \;\;\;\;\;\implies\;\;\;\;\; r_{11}=\frac{3}{4},\; r_{12}=\frac{3}{2}, r_{22}=0 $$
Computing the log-odds $s_{ij} = \log_2( r_{ij} )$ gives the same values as you get.

So why is $r_{11} > r_{12}$? Well, notice they have the same normalizer, i.e. $e_{11}=e_{12}$. So the difference comes from the fact that $ q_{11} > q_{12} $, the empirical pair distribution. Essentially, because of the way we computed $q_{ij}$, we consider there to be only one pair QQ but two pairs of QS.
I would also note that sometimes results are a little unintuitive for very small samples (data sparsity throws off the statistics essentially).


Why are Chromosome Territories important? Chromosomes occupy discrete regions of the nucleus, referred to as 'Chromosome Territories'. This spatial organization is emerging as a crucial aspect of gene regulation and genome stability in health and disease.

But how is this the case when:

Most eukaryotes seem to have Chromosome Territories, but yeast S.
cerevisiae is an exception to this.

So if some eukaryotes do, and some do not, what information do Chromosome Territories provide? Some literature uses the phrase 'non-random chromosome territory arrangements'. Thus, I am confused.
Chromosome territories are randomly arranged in some eukaryotes.
How are chromosome territories crucial for gene regulation and genome stability in health and disease in some  eukaryotes, but random in other eukaryotes?

First, this idea was discredited or ignored during several decades, some studies suggest that CT is random in some eukaryotes that isn't necessary the truth. It is not easy at all to determine is CT are random or not
Second, not all eukaryotic organism are the same. Plants and Fungi have cell walls, animals do not. Fungi can have a dikaryotic cell or even undergo somatic hybridisation.
Third, "chromosomes are more unfolded in lower eukaryotes such as yeast."Chromosome Territories: The Arrangement of Chromosomes in the Nucleus
This article does not mention that S. cerevisiae is an exception, on the contrary "and may even hold for single-cell eukaryotes, such as budding and fission yeast".
Thank you for the question, I learnt a lot while searching for an answer