HSL Lightness vs Eye sensitivity In a monochromatic spectrum, is the human eye equally able to distinguish between lighter colors just as it is in distinguishing between darker colors? I mean is there really a linear relationship between the Lightness property in the HSL color model and the perceived brightness?

No, the L axis in the HSL color space does not really correspond to lightness as perceived by the human eye, except in the very crudest sense that, for given values of the H and S components, increasing L produces an increase in the perceived lightness.

The L component of the standard HSL color space is simply calculated as the average of the lowest and the highest RGB component of the color (in whichever RGB color space in being used): $$L = \frac{\min(R, G, B) + \max(R,G,B)}2$$

This definition alone should make it obvious that the L value cannot correspond to perceived lightness, since it completely ignores the middle one of the three RGB channels.  Thus, the color (R=0, G=0, B=1), i.e. pure $\color{#0000ff}{\rm blue}$, has exactly the same L value (0.5) as the color (R=0, G=1, B=1), i.e. $\color{#00ffff}{\rm cyan}$, yet it's obvious at a glance that the latter color is visually much brighter.

Indeed, the HSL color space doesn't even try to match the perceptual lightness of the colors; rather, the definition of the L channel is chosen because it has the convenient feature that it maps black to L=0, white to L=1, and all the six maximally saturated pure RGB colors (red, yellow, green, cyan, blue and magenta), despite their wide perceptual lightness differences, to L=0.5.

A much better approximation to the perceived lightness of a color is the luma Y', which is defined as a weighted average of the RGB channels.  The precise weights depend on the definition and the RGB color space used, but a common choice (from ITU-R Rec. 709) is: $$Y' = 0.2126\, R + 0.7152\, G + 0.0722\, B$$

The weighs are chosen to account for the different perceived lightness of the different RGB primary colors.  A striking feature is the that the green component alone accounts for over 70% of the luma, nearly ten times as much as the blue component.  Yet a visual comparison of $\color{#0000ff}{\rm 100\%\ blue}$ with $\color{#00ff00}{\rm 100\%\ green}$ does clearly confirm that this choice of weights is justified: the pure green appears much brighter than the blue, and almost as bright as the cyan (which is their sum) above.

However, the definition of the luma still ignores the non-linearity of both the standard RGB color spaces (such as sRGB) and the human eye.  While these two effects partly cancel out each other, allowing luma to be used as a reasonable approximation of perceptual lightness, for truly accurate results they need to be accounted for.  This involves several steps:

Convert the RGB color into a linear color space.  For sRGB, the following formula may be used: $R_L = f(R), G_L = f(G), B_L = f(B)$, where: $$f(C) = \begin{cases}C / 12.92 & \text{if } 0 \le C \le 0.04045 \\ ((C + 0.055) / 1.055)^{2.4} & \text{if }  0.04045 < C \le 1 \end{cases}$$ (Here, $R$, $G$ and $B$ are the sRGB component values, and $R_L$, $G_L$ and $B_L$ the linear ones, both scaled to the range from 0.0 to 1.0.)  Alternatively, a very close approximation to the formula above is given by simple gamma-expansion with $\gamma = 2.2$: $f(C) = C^{2.2}$.
Calculate the relative luminance as a weighted average of the linear RGB component values: $$Y = 0.2126\, R_L + 0.7152\, G_L + 0.0722\, B_L$$ (The weights are exactly the same as for the luma formula above, because that's where they come from; the luma calculation just blindly applies them to the gamma-compressed RGB values.)
Convert the relative luminance value into an approximation of the percieved lightness, using something like the CIELAB formula: $\ell^* = 1.16\, g(Y) - 0.16$, where: $$g(Y) = \begin{cases} \tfrac13 \left(\tfrac{29}{6}\right)^2 Y + \tfrac{4}{29} & \text{if } 0 \le Y \le \left(\tfrac{6}{29}\right)^3\\ Y^{1/3} & \text{otherwise} \end{cases}$$ (Note: In the CIELAB standard, the $L^*$ value ranges from 0 to 100, but for the sake of consistency, in the formula above I chose to define $\ell^* = L^* / 100$, so that its range is also from 0 to 1.)


Why is it so important to avoid infection of lacerations to the scalp? There is supposedly something unique with regards to infections of the scalp, although I cannot remember, perhaps it was to do with the CSF and its build up? I have scoured the internet for hours but have not found an answer.

Deep lacerations of the scalp that penetrate the fourth layer (area of loose connective tissue) have an increased risk of infection. This is because pus and blood spread easily within it. This can easily pass into the cranial cavity along the emissary veins Therefore, infection can spread from the scalp to the meninges and could lead to meningitis.


Does catching a cold give you an "effective" advantage against future colds? By effective advantage I mean that if I catch a cold now and then recover fully, does this actually reduce my probability of catching a future cold. I understand that the body can build up anti-bodies and such, but pathogens also have the ability to mutate and I would assume that anti-bodies levels decrease over long periods of time. I am not a biologist! So feel free to correct my poor assumptions.

Thus taking those factors into account, are there models or data to argue that catching a cold gives me a future advantage over avoiding the cold altogether?

Short answer: no.

The "cold" is a common term for symptoms caused by dozens of different viruses. Even the canonical "cold" virus (rhinovirus) has large numbers of strains.

Exception to the short answer: Getting a cold might be effective against similar strains of the same virus.

Most of the time, future colds will be due to a different strain or a different virus. Best protection is to block unused/vulnerable receptors in the nose.


What does it mean to protect RNA polymerase? From this paper

  However, based on the strong interaction between NusA and RNAP, we propose that the chaperone activity of NusA could provide more direct and concentrated protection for RNAP under stress, i.e., NusA could simultaneously act as a latent protector of RNAP during transcription elongation and termination.

By "protection" the authors mean that in the presence of NusA, some proteins are less prone to aggregation after heat shock. "Protection", in general, could also refer to stabilization i.e. reduction in the degradation rates of the protein.

To detect the influence of NusA on heat-induced aggregation, we used
lactate dehydrogenase (LDH). LDH was incubated at 48°C in the absence
or presence of NusA. As shown in Fig. 2b, LDH slowly aggregated at
48°C without the protection of NusA. However, when this experiment was
performed in the presence of NusA, aggregation was visibly reduced.
These results suggest that NusA also protects unfolded proteins from
irreversible aggregation during thermal stress.
...
...
In E. coli, RpoA and RpoB, the major components of RNAP, are prone to
aggregation under heat stress in vivo. They were reported to interact
with GroEL and DnaK, mainly for the protection from aggregation or
refolding into a nonnative state48,49. However, based on the strong
interaction between NusA and RNAP, we propose that the chaperone
activity of NusA could provide more direct and concentrated protection
for RNAP under stress, i.e., NusA could simultaneously act as a latent
protector of RNAP during transcription elongation and termination.


How does formaldehyde/PBS or methanol fixation of cells affect lysosomal pH? The question is fairly simple - does formaldehyde or methanol fixation in preparation for immunocytochemistry/immunofluorescent staining affect the pH of the lysosomes?

Some background: I'm trying to look at the intracellular trafficking of a fluorescently-labeled lysosomal enzyme. Cells are grown in vitro and treated with the labeled protein, which is taken up into the cells via receptor-mediated endocytosis. The protein-receptor complex targets the late endosome-lysosome pathway, where eventually the acidic pH of the lysosome causes the two to dissociate and the receptor to recycle, while the enzyme stays and does its thing. I've labeled the enzyme with two different dyes - Alexa Fluor 488, which is supposedly pH-insensitive between 4 and 10, and pHrodo Red, which has greatly-increased fluorescence as the pH drops. Alexa488 is the brightest of the Alexa dyes, and is widely used in all sorts of applications. pHrodo is not as bright (as far as I can tell, it's been difficult to find comparisons), but its pH-dependence helps lower the effect of non-specific extracellular binding, and it seems to work in my system so far.

So what's the problem? I'm developing an assay that will measure the ability of certain substances to block the uptake of this enzyme into the cell. Since I'll be measuring a lack of signal, the higher I can get the uninhibited signal to be, the better. Like I said, pHrodo works OK, but it could be better. The problem is that my Alexa-labeled protein has an extremely low signal to noise ratio, when I would have expected the exact opposite. I'm wondering if, in my system, the Alexa dye really is somewhat pH-sensitive, and is not fluorescing as well when in the acidic lysosome. I'm encountering a few other issues as well, and while before I was performing live-cell imaging, I'm starting to toy with the idea of fixing the cells first, as that will positively impact some other things I want to try.

Hence my question: Will fixing the cells with 4% formaldehyde in PBS (standard ICC/IF protocol) affect the pH of the lysosomes? Would methanol fixation do the same thing? Any other suggestions for increasing signal?

In my opinion, cell fixation shouldn't change the pH. However unbuffered formalin will oxidize and lower the pH, but using PBS should buffer around pH 7.
Maybe Glutaraldehyde fixation would also be an option, if the others are not working...

I found this website by leica very useful, maybe it will also help you:

  http://www.leicabiosystems.com/pathologyleaders/fixation-and-fixatives-2-factors-influencing-chemical-fixation-formaldehyde-and-glutaraldehyde/


How do firing patterns arise from the activity of many ion channels? In his answer to another question, Bryan Krause says:

  Ion channels don't exhibit any firing patterns: neurons exhibit
  firing patterns that depend on all the channels present [...].

I understand it this way: The observable and measureable firing pattern1 of the neuron (created at the trigger zone) is the linear superposition of tiny "firing patterns2" of all the (voltage-gated) ion channels at the trigger zone, which in turn depend on the probabilities of opening and closing which are the same for all ion channels of the same type and obey some Hodgkin–Huxley-like law. These probabilities correspond directly to the shape of firing pattern1.

The rhythm with which each single sodium channel opens and closes ("firing pattern2") doesn't have to mimick firing pattern1 exactly, only roughly and probabilistically: the open-close-ticks must occur near to the spikes of  firing pattern1, but not exactly and not at every spike. And some complete outliers are allowed. The rest is superposition.

Seeing things this way, indiviudual ion channels do exhibit "firing patterns2", but these may look quite different than firing pattern1 (although not completely).

  Is this kind of reasoning correct?

If so: Can the following conclusion be drawn: The time scale of a firing pattern1 depends on the number of ion channels at the trigger zone? This might be seen when looking at the rise time of a single action potential: If there is only one sodium channel, rise time will be larger, if there are many, it will be smaller. Is this correlation strictly linear?

Typically the activities of the ion channels are not called firing patterns as in neuroscience we refer to "firing" when we mean the elicitation of action potentials (spikes) but yes: Whenever an AP was fired a sufficient amount of sodium channels had to be open and therefore I thing your reasoning is correct. In other terms what you are saying is that the effective channel conductances change during an action potential.

On your conclusion: In the regime of natural parameters the time scale of firing pattern 1 mostly depends on the time constants of the voltage gated ion channels and not so much on the absolute number of channels (especially if all the conductances would scale equally).
In the world of Hodgin-Huxley like coupled- and nonlinear-dynamical systems the voltage does not scale strictly linear with increasing the participating max. conductances. The interplay of max. conductance and temporal gating dynamics resulting in the effective conductance itself depends on the voltage and there are nonlinearities. So the correlation between the number of channels and the AP rise time is not expected to be strictly linear.

See the figure for a little example: I tested my reasoning by increasing the max. conductance for the sodium channel of a simple HH model and checked the max. steepness of the voltage (normalized by peak voltage).

Hope that answers your question(s).


Are there known 3- or 4-nucleotide RNA linkers with no RE sites? Question is rather self-explanatory. I'm looking for a non-cleavable RNA sequence to act as an RNA linker.

I mention 3- or 4-nucleotides only, but making such a sequence with 2 nucleotides is rather easy as seen below, but I've encountered some difficulties in transcription.

  GAGGAAGGGAAAGGGGAAAAGGGGGAAAAA...

This also works for just about any random sequence of G's and A's.

I don't know the answer, but you could simply brute force the answer by generating all possible combinations of 3- or 4-nt length sequences, and comparing against the restriction enzyme database (REbase).

It would not take long to do. There are $ 3^4 $ and $ 4^4 $ combinations, respectively. Depending on your purpose, it might be possible when not considering engineered restriction enzymes (which are not likely to have recognition sequences found in nature).


Is there a database providing information about optimum temperature and inactive temperature of enzymes? I want to know optimum and inactive temperature of some enzyme, but I can't find these information in NCBI, wiki or UniProt. So I want to know if there are some database which provide these information?
Thanks for help.

UniProtKB has annotations for biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.
http://www.uniprot.org/help/biophysicochemical_properties

Such annotations are currently available for about 6800 reviewed entries: http://www.uniprot.org/uniprot/?query=annotation%3A%28type%3Abiophysicochemical_properties%29&sort=score

More specifically, temperature dependences is annotated in about 2000 entries: http://www.uniprot.org/uniprot/?query=annotation%3A%28type%3A%22temperature+dependence%22%29&sort=score


Does Japan have an ageing population? I often hear Japan has a declining/ageing population.
It seems to be the prime example for this kind of thought.
Yet after moving to Japan and after having been there for travel several times already. And in comparison with my native country Germany as well as Europe in general, I think this concept seems questionable.
While I hardly see any children outside in Germany and it's mainly parents with one child.
Everywhere I go in Japan I meet a lot of children. Especially in the greater Tokyo area, if I go to restaurants there's always a bunch of kids. And usually you see at least two children per parents, if not three.
I can understand that in general this concept might be true but might not be applicable for bigger cities.

Where does the concept come from? Is there any proof it's actually true?

I hate to sound rude, but you could easily answer this yourself with even the most minimal look into well-tabulated demographic information, rather than highly non-representative observations. About 13% of Japan's population is 0-14 years old, the third lowest fraction in the world. (https://data.worldbank.org/indicator/SP.POP.0014.TO.ZS ; easy to find with Google)  The fraction of the population over age 65 is 28%, the highest in the world. (https://data.worldbank.org/indicator/SP.POP.65UP.TO.ZS?most_recent_value_desc=true) The population density is high, so you'll certainly see more kids than in many other countries, though not proportionally more. I will leave it as an exercise to look up the numbers for Tokyo itself.


Do Gametes contain mitochondria/chloroplasts from their parent cell? It has now been established (according to the Cambridge A level text book) that

  organisms form a symbiotic
  partnership, typically by one engulfing the other
  – a process known as endosymbiosis. Dramatic
  evolutionary changes result.
  The classic examples, now confirmed by later
  work, were the suggestions that mitochondria and
  chloroplasts were originally free-living bacteria
  (prokaryotes) which invaded the ancestors of modern
  eukaryotic cells (cells with nuclei).

It also states that

  It was also discovered in the 1960s that mitochondria
  and chloroplasts contain small, circular DNA molecules,
  also like those found in bacteria

and lastly

  The DNA and ribosomes of
  mitochondria and chloroplasts are still active and
  responsible for the coding and synthesis of certain vital
  proteins, but mitochondria and chloroplasts can no longer
  live independently.

So my question is:

Is this DNA found in the mitochondria and chloroplasts coded for in the host's (animal's or plant's) DNA.

If not are there fully formed mitochondria and/or chloroplasts in all gametes (obviously chloroplasts only in the plant gametes) which were transferred directly from the parent who had them transferred directly from their parent and so on?

If so are all the mitochondria and chloroplasts of one type identical in a organism? Are they almost identicle in families (of organisms not the classifictaion Family)?

Is this DNA found in the mitochondria and chloroplasts coded for in the host's (animal's or plant's) DNA.

No, the DNA contained in these organelles it not a subset of the nuclear genome. However, part of the original genome of the prokaryote has been moved to nuclear DNA. That is why, as you cited, they "can no longer live independently."

  If not are there fully formed mitochondria and/or chloroplasts in all gametes (obviously chloroplasts only in the plant gametes) which were transferred directly from the parent who had them transferred directly from their parent and so on?

As the child organism would eventually need these organelles, and they can only be inherited, at least one of the gamete must contain them.

For the chloroplast, the general rule is that only one of the gamete provides it. For example, in gymnosperm it is the male gamete (pollen), in angiosperm, it is the female gamete (ovule). Either it is just not present in the other gamete, or a specific exclusion mechanism makes it mono-parentally inherited.

Mostly the same for the mitochondria, with the caveat that (motile) spermatozoa contain mitochondria for their metabolic functions (energy to move), but these are discarded when forming the zygote, and only the maternal mitochondria are inherited. (In plants, mostly maternal too with exceptions)

This does mean that there is a lineage of organelle on one of the parent's side, up to the most recent common ancestor (approximately, the first individual of the species). In humans, this translates to a presumed Mitochondrial Eve from which all human mitochondrial DNA descends from.

  If so are all the mitochondria and chloroplasts of one type identical in a organism? Are they almost identicle in families (of organisms not the classifictaion Family)?

Every mitochondrion of an individual organism comes from the stock of mitochondria of the zygote, through replication. They are thus very similar, except for cell specialization (giving particular morphology to the organelles), and possible mutations. Same for the chloroplast.

Mitochondria (and chloroplasts) are basic components of the eukaryotic cell, providing essential functions  which are highly conserved in a species, let alone related individuals.

However, this does not means the DNA of these organelle is the same for every individual : different sequences may give the same protein, or mutation may affect non-coding segment of the genome. This is the basis for genetic genealogy, retracing family lineage though analysis of DNA, including mitochondrial DNA.


How does HBeAg change to Anti-HBe in acute hepatitis I am thinking this figure

which can also be drawn like this

How does HBeAg change to Anti-HBe?

There are some triggers that stimulate Anti-HBe production after HBeAg level is done.
I think they can Anti-HBc.
There must be other mechanisms too.

I'm not sure that I have understood the question but ...

HbeAg is a secreted variant of HbcAg (the core antigen of HBV). Unlike HbcAg, HbeAg is found in the blood. I believe that it is produced as a result of a splice variant of the corresponding RNA.

The phenomenon described in these Figures is an example of seroconversion. Before seroconversion the antigen is detectable in the blood but there is no antibody directed against it; after seroconversion there is antibody but no antigen.


Do drugs always degrade after they have passed their expiration date? I have been wondering for some time whether several drugs really have an expiration date.

Let's narrow the scope and think about only "common" drugs, e.g NSAIDs, antibiotics etc.
For example, would antibiotics in the pills get deactivated or decomposed?

Drugs do not have to degrade after their expiration date and passing the expiration date has more than one possible meaning.

First of all chemical compounds vary in their susceptibility to breakdown over time.  If they are kept away from oxygen, high temperatures (or kept in very low temperatures), and they are of a robust chemical nature, they might be stored for much longer than their expiration date and remain just as strong.

Over time, pharma compounds will chemically break down and lose their potency.  In many cases, you will find that they simply don't do anything when you take them.  This link cites a study that many drugs can retain their potency 15 years after they are made.

There are important exceptions.  Two examples are tetracycline and acetaminophen (tylenol) whose breakdown products can increase the tendency for these drugs to induce liver damage.


What do blue cone cells add to visual function? First of all, I saw this other question in the SE sites with a good answer, but I didn't find an explanation about the blue cones specifically.

So most human beings have 3 types of cones (cells specialized in color sensing : blue, green and red).
While it may seem obvious that the red and green-sensing cones are an evolutionary advantage (given our natural environment and how we ate for millenia), for instance to locate fruits and differentiate ripeness, I can't find a clear advantage in having the blue cones. Blue doesn't seem to relate to anything like food, predators, sexuality. Am I missing an obvious utility ?

Let's try to imagine what happens if we remove blue cones :

The sky would look gray. I don't see a survival issue there.
We wouldn't be able to make a difference between yellow and white (white = green + red in this case). Is it a big deal ?

I have the reflex to think "if a character is widespread, there must be a good reason". It seems I should rather say "there must be an explanation".

So I'm trying to think differently, and here are other possible approaches to address this question :

I read that dogs have only blue & yellow cones. Maybe our ancestors had only two cone types, including blue, then a third type appeared and blue stayed just because it wasn't a problem to keep it ?
What we call visible spectrum is in fact the only part of the spectrum that can go through air and water (in the eye) without being absorbed (link). Blue cones would be there just because "hey there's something to see" ?
For a long time we had only fires to look at, at night. No TV or screen with Q&A sites to consult. Is it possible that some of our ancestors stared for too long a hot fire, losing green and red cones ? Those with blue cones were not totally blind and managed to reproduce ! (this one is... almost a joke)

Sadly these approaches don't really convince me.

ADDITION : here is a visual example to see what happens if we remove blue information from an image (original image taken here). The image without any blue (middle) is confusing because it makes you think we could see yellow (while yellow wouldn't be different from white). That's why I added the image on the right, containing only information from red and green channels (the blue channel is replaced by min(Red,Green)). I think it illustrates well that blue isn't important, at least for vegetables and fruits !

Short answer
Primate color vision started off with photosensitive cells detecting medium to long wavelengths (M/L cones detecting greens and reds) and short wavelengths (S cones most sensitive to blue). By neurophysiologically weighing their relative contributions the full spectrum (red, orange, yellow, green, blue and indigo) can be detected by dichromats. Addition of a slightly different M/L cone and generating separate M and L cones increases the resolution of color vision in the medium and long wavelengths, which is thought to enhance color discrimination useful for foraging fruits. Indeed, blue in itself is not needed for this task. However, missing the blue cones would eliminate a large proportion of the visual spectrum.

Background
Evolutionary spoken, primate vision started off with dichromatic vision. These early dichromats had retinas with one type of cone sensitive to medium-to-long wavelengths (M/L cones) and one type sensitive to short wavelengths (S cones) (Jacobs, 1996). This organization determines the dynamic range of color vision, i.e., to see colors from short wavelengths (greens and blues) to long wavelengths (red and yellows). Weighing their relative contributions by neural networks in the retina allows the intermediate wavelengths to be resolved.

Later in evolution, some diurnal species had a gene duplication on their X chromosome, generating a M/L duplicate gene (Jacobs, 2009). Small mutations in these genes eventually paved the way for two closely related M/L opsins, namely one a little more sensitive to longer wavelengths (L opsin) and one to slightly shorter wavelengths (M opsin). The dynamic range of color vision still depends heavily on the S opsin in the blue cones, as the M and L opsins have absorbance spectra much closer to each other (Fig. 1). The benefit of two opsins with nearly identical absorbance spectra is a higher color discrimination ability (higher color resolution) in the medium to long wavelengths. High discriminating power in the red-yellow-green part of the spectrum is thought to be beneficial for diurnal fruit foraging primate species (Jacobs, 1996). Note that cones need a lot of photons to operate; nocturnal primates are typically dichromats and they will not benefit anyway from another M/L cone.

For fruit foraging alone, the L and M cones do a pretty good job, as your example shows. However, there is more to the eye than food alone. Eliminating the blue cones would substantially narrow down the dynamic range of color vision. Further, evolution started off with S and L/M cones and added another M/L cone to that existing system. Evolution didn't start off with a blind ape and the goal to generate the perfect fruit forager; no it started off with a dichromat and over time improved its ability to seek food during daylight.

Fig. 1. Absorbance spectra of the different opsins. source: Kevin MD

References
- Jacobs, PNAS (1996); 93: 577-81
- Jacobs, Philos Trans R Soc Lond B Biol Sci (2009); 364(1531): 2957–67


What is happening physically when I get sleepy and when I wake up? After a week of too little sleep, I slept about 12 hours last night to "catch up". It made me wonder: what is happening physically that signals that I'm done sleeping,  or conversely,  that I need to sleep. I read this question and its answers, which explain how brain waves indicate different sleep stages: Why sleep? No, actually, why wake?

But what causes the changes in these brain waves? I'm curious about the mechanism by which my body determines that it needs sleep, and not just a set amount,  but a specific amount based on my previous week's lack of sleep. is it something in my brain or is it a hormone or something else?

During sleep the cerebrospinal fluid clears out the waste products of brains cells. Sleep fragmentation or sleep deprivation can prevent this process, or reduce its efficiency. So I think the accumulation of waste products cause that you have to sleep more after sleep deprivation and extreme sleep deprivation (e.g. by fatal insomnia) can cause death. Low quality sleep and sleep deprivation can cause or worsen both neural (e.g. Alzheimer's disease),  and metabolic diseases (e.g. diabetes mellitus, etc...), so you should avoid it, if you can (I cannot :D).

Daily sleep is regulated by the circadian clock. Many hormones can affect that clock, e.g. melatonin (dependent on blue light), insulin, etc...

  The conservation of sleep across all animal species suggests that
  sleep serves a vital function. We here report that sleep has a
  critical function in ensuring metabolic homeostasis. Using real-time
  assessments of tetramethylammonium diffusion and two-photon imaging in
  live mice, we show that natural sleep or anesthesia are associated
  with a 60% increase in the interstitial space, resulting in a striking
  increase in convective exchange of cerebrospinal fluid with
  interstitial fluid. In turn, convective fluxes of interstitial fluid
  increased the rate of β-amyloid clearance during sleep. Thus, the
  restorative function of sleep may be a consequence of the enhanced
  removal of potentially neurotoxic waste products that accumulate in
  the awake central nervous system.

2013 - Sleep Drives Metabolite Clearance from the Adult Brain
2013 - Sleep Facilitates Clearance of Metabolites from the Brain: Glymphatic Function in Aging and Neurodegenerative Diseases

  According to the traditional understanding of cerebrospinal fluid
  (CSF) physiology, the majority of CSF is produced by the choroid
  plexus, circulates through the ventricles, the cisterns, and the
  subarachnoid space to be absorbed into the blood by the arachnoid
  villi. This review surveys key developments leading to the traditional
  concept. Challenging this concept are novel insights utilizing
  molecular and cellular biology as well as neuroimaging, which indicate
  that CSF physiology may be much more complex than previously believed.
  The CSF circulation comprises not only a directed flow of CSF, but in
  addition a pulsatile to and fro movement throughout the entire brain
  with local fluid exchange between blood, interstitial fluid, and CSF.
  Astrocytes, aquaporins, and other membrane transporters are key
  elements in brain water and CSF homeostasis. A continuous
  bidirectional fluid exchange at the blood brain barrier produces flow
  rates, which exceed the choroidal CSF production rate by far. The CSF
  circulation around blood vessels penetrating from the subarachnoid
  space into the Virchow Robin spaces provides both a drainage pathway
  for the clearance of waste molecules from the brain and a site for the
  interaction of the systemic immune system with that of the brain.
  Important physiological functions, for example the regeneration of the
  brain during sleep, may depend on CSF circulation.

2014 - A new look at cerebrospinal fluid circulation

  Sleep fragmentation is present in numerous sleep pathologies and
  constitutes a major feature of patients with obstructive sleep apnea.
  A prevalence of metabolic syndrome, diabetes and obesity has been
  shown to be associated to obstructive sleep apnea. While sleep
  fragmentation has been shown to impact sleep homeostasis, its specific
  effects on metabolic variables are only beginning to emerge. In this
  context, it is important to develop realistic animal models that would
  account for chronic metabolic effects of sleep fragmentation. We
  developed a 14-day model of instrumental sleep fragmentation in mice,
  and show an impact on both brain-specific and general metabolism. We
  first report that sleep fragmentation increases food intake without
  affecting body weight. This imbalance was accompanied by the inability
  to adequately decrease brain temperature during fragmented sleep. In
  addition, we report that sleep-fragmented mice develop glucose
  intolerance. We also observe that sleep fragmentation slightly
  increases the circadian peak level of glucocorticoids, a factor that
  may be involved in the observed metabolic effects. Our results confirm
  that poor-quality sleep with sustained sleep fragmentation has similar
  effects on general metabolism as actual sleep loss. Altogether, these
  results strongly suggest that sleep fragmentation is an aggravating
  factor for the development of metabolic dysfunctions that may be
  relevant for sleep disorders such as obstructive sleep apnea.

2012 - Sustained sleep fragmentation affects brain temperature, food intake and glucose tolerance in mice
2014 - Sirtuin 3: A Molecular Pathway Linking Sleep Deprivation to Neurological Diseases

  Inadequate sleep simultaneously modulates the levels of multiple
  hormones that govern metabolism, In general, with sleep deprivation,
  the following hormones are decreased: insulin, growth hormone (GH),
  growth hormone releasing hormone (GHRH), and leptin levels. In
  contrast, ghrelin and somatostatin are increased. Essentially,
  hormones that signal that the body has plenty of energy are decreased,
  while those that signal energy need are increased. Experiments
  utilizing knockout animals as well as pharmacological agonists,
  antagonists, and immunodepletion of the proteins, illustrate that
  these hormones affect sleep regulation. Diabetic rats have decreased
  sleep time and consolidation while replacement of insulin increases
  increases slow-wave sleep.

2013 - The Genetic Basis of Sleep and Sleep Disorders (book)

  In humans, melatonin is produced by the pineal gland, a small
  endocrine gland[26] located in the center of the brain but outside the
  blood–brain barrier. The melatonin signal forms part of the system
  that regulates the sleep–wake cycle by chemically causing drowsiness
  and lowering the body temperature, but it is the central nervous
  system (specifically the suprachiasmatic nuclei, or SCN)[26] that
  controls the daily cycle in most components of the paracrine and
  endocrine systems[27][28] rather than the melatonin signal (as was
  once postulated).

wikipedia - melatonin


What happens if someone with mutations to alcohol dehydrogenase (ADH) drinks alcohol? ethanol then doesn't get converted to acetaldehyde.

in fact, could someone KO'ed for ADH be resistant to methanol poisoning?

People, which have no ADH wouldn't be able to process methanol. Since the specificity of the ADH is higher for ethanol you get quite large amounts of ethanol for days (until the methanol level is under a specific level). Another possibility is to treat patient with the ADH inhibitor Fomepizole.

This also makes problems for the ethanol metabolization, but according to this paper ("The biochemistry of alcohol metabolism - a brief review") there are two other pathways of breakdown. One takes place in the peroxisomes and utilizes catalase and hydrogen peroxide (but is limited by the availability of peroxide), the other take place in the smooth endoplasmatic reticulum and uses the Cytochrome P450 enzyme.

I am not sure, if complete losses of ADH really happen (haven't found any reference) but mutations in this enzyme are quite common leading to a lower enzyme activity.


Which mammals cannot synthesize taurine? It is fairly common knowledge that domesticated cats cannot synthesize the compound taurine. Other mammals seem to be able to synthesize taurine from cysteine [source]. Are there other mammals that lack the ability to synthesize taurine?

It is a misconception that cats cannot synthesize taurine.

Cats can synthesize taurine, just like other mammals, but not enough of it to make up for an entirely taurine-deficient diet. Cats (and other mammalian carnivores) would have consumed a taurine-rich diet in the ancestral environment. It is only when they are fed vegetable/fruit/grain-derived foods that they show symptoms of taurine deficiency--because those foods have low quantities of taurine and other taurine precursors.

Other domesticated or captive carnivorous mammal species are at risk of taurine-deficiency if they are fed vegetable-derived foods, though members of the cat family (Felidae) are particularly susceptible.

Primary reference: This 2003 paper about taurine concentrations in animal feed, especially the 'Discussion' section.

  Taurine  is  an  essential nutrient of cats because the rate of taurine synthesis from its dietary sulphur amino acid precursors, cysteine and methionine, is much less than the extent of loss through faecal bile
  acids  and  urine  (Knopf et al.,  1978).  From  an  evolutionary  standpoint,  taurine  was plentiful  in  the  diet  of  a  true  carnivore,  as  high  concentrations  of  taurine  are  found  in muscle  tissue. However,  as  most  domesticated  felines  normally  do  not  consume  living
  prey, they are at risk to become taurine-deficient if not adequately supplied in the diet.


How many cells need to be damaged before a human can feel it as pain? I'm guessing the answer to this question is rather large. Skin cells die all the time, it seems, and that never registers as painful. But suppose you rupture or otherwise destroy a group of cells, say in the dermis or something, which enough precision to be able to specify the exact count. How many would you have to destroy before it would be perceptible? What if you add a delay between the destruction of each cell in the group? If it was staggered in time, would that make it imperceptible again?

Although any number estimation would be inaccurate, I can think on two factors that can influence the count.

Cells location: Pain is trigger when specialize cells (Nociceptors) fires action potentials. The density of those nociceptors is greater in the tip of your finger than in your back. So the number of cell damage that trigger the pain would be different in those areas too.
Cell death rate: The delay that you mention is a key factor. Slow death like the normal on skin is done by a regulated mechanism (Apoptosis), in this process the cellular components are recycled. In fast cell death, the cellular components are released causing inflammation, which increases the nociceptors sensitivity.


Data on Gene Position in Human Genome I am trying to get some data on gene position in the human genome and I need some help

What I tried

I downloaded ftp://ftp.sanger.ac.uk/pub/gencode/Gencode_human/release_18/gencode.v18.annotation.gtf.gz

I am only interested in gene position, so I kept only the first columns.

awk -F "." '{print $1}' /Users/remi/Downloads/gencode.v18.annotation.gtf  >> HumanGenomePositions.txt

This operation will take a few minutes. The file contains information on exon position and transcript. I subsetted the table to get only the lines that concern genes

sed -i.bak '/gene/!d' HumanGenomePositions.txt

I am left with 57445 entries. 9872 are annotated by ENSEMBL and 47573 are annotated by HAVANA. Note that there is partial overlap between the two. According to Church et al. 2009, there are 19042 annotated genes in the human genome (reported from bionumbers). There is obviously something I am getting wrong!

Question

Can you help me to get data on gene positions in humans in a handy format (see below)?

start   end
15648   65487
129841  124984
...

I recommend to filter using transcript_type value from description column. You need only proteine_coding genes. Now you have extra ~10K unprocessed pseudogenes, ~5K antisense genes, ~4K miRNA, ~7K lincRNA and more than thirty other categories of unprocessed pseudogenic stuff.

As far as I know current release for GRCh37 is 19th version, not 18.


Can replication occur if DNA is methylated? Can a methylated strand of DNA be replicated without removing methylation? Does it make any difference if the strand is methylated or not (during replication)?

Absolutely.  It's a pretty cool process, actually.  Most (well...) DNA methylation occurs in the context of what are called CpG; that is, a C (Cytosine) followed by a G (Guanine).  Because C and G are the Watson-Crick pair for each other, the sequence on the opposite strand will also be CG.  Usually, both Cs are methylated, which turns out to be rather critical for maintenance of methylation.

DNA replication occurs through a semi-conservative mechanism, which means each old, original strand is copied and paired with a new strand.  The new strand has no methylation on it, however; it is at this point that the enzyme DNA methyltransferase (DNMT1, specifically) comes into play.  DNMT1 finds the CpGs methylated on one strand ("hemimethylated") and methylates the other strand, providing complete inheritance.  Here is a nice summary, and this is a review that (briefly) summarizes the evidence that CpGs may play a role in irigins of replication (the jury's still out).


How many Endogenous Retroviruses do we share with other primates? Is there a list of Endogenous Retroviruses that we share with other primates? I would like to map all (or most) of them into a hierarchy and see how it fits in our evolutionary branch.

There are several papers that cover this. Briefly, humans share the vast majority of their ERVs with other primates, but not all; and this is mainly because other primates have acquired ERVs that humans have not (rather than humans acquiring new ERVs themselves).  The third link, in particular, seems to cover your proposed reconstruction and concluded that in general "these sequences gave trees that were consistent with the well established phylogeny of the old world primates".

Divergent Patterns of Recent Retroviral Integrations in the Human and Chimpanzee Genomes: Probable Transmissions between Other Primates and Chimpanzees
The decline of human endogenous retroviruses: extinction and survival
Constructing primate phylogenies from ancient retrovirus sequences


Does the eye image interval refresh? It's known the human eye takes 24 images per second. But does this refresh?
For example after sleeping.

Or will it always be the same interval?

I talk about when the eye takes the images. So it are 24 images in the second, but this second is not defined. It can start at 09:00:00.00 or 09:00:00.50. Will this change after taking a sleep?

Hope it is clear what I'm talking about.

Human eyes do not take 24 images per second. Refresh done in parallel, each pixel separately, and the rate depends on the rate of color changing.

So, the work of eye is closer to MPEG encoding than to uncompressed AVI.


Can a plant be programmed to produce any arbitrary object? I'm wondering if a plant can be programmed (by modifying its genes) to grow into any shape that it's programming instructs.

I understand that a plants genes are its instructions of how to convert the nutrients in the soil into the plant we see. So, instead of producing an apple tree or a giant sequoia, couldn't a plant be programmed to shape itself into a house, desk, or even at a stretch of the imagination, a bioship?

I'm looking for any links, or explanations of why this could/couldn't be done by anyone with more experience than I that could guide my research.

I am hoping that a plant behaves just like any other system. That it has inputs (nutrients, sunlight etc.) a function that describes it (its genes) and an output, the plant that grows. With this in mind, I suppose it would only be a matter of modifying the genes to produce the desired output (with the constraint being the available input).

Thank you,
Paul

It could not fit in a comment...

1) Any material have some physical limitations and living tissue are not exceptions. A plant cannot resist to very high pressure without changing shape for example. Outside of these problems of material sciences I think the major considerations are technical…

2) It is possible to influence the shape of a plant by changing its DNA code, changing its physical and chemical environment (micro or macro environment) or by injecting some substance. Today we might be able to influence the number of branching of certain plants species for example. But we are terribly far from having enough knowledge in biology (in genotype-phenotype map, in biochemical pathway) in order to transform a dandelion into a shopping mall! Even we had already described all chemical pathway linking genes to phenotypic traits, it is immensely more complex to think of which kind of DNA sequence might transform a plant into something that is so different.

I don't know if anyone has ever created a totally synthetic (and not copied from already existing sequences) DNA sequence and could predict the impact it would have on the organism phenotype. Some people were able to create a totally artificial self replicating RNA though.

Note: Some people play with the properties of the DNA molecule in order to create various tissues. This might interest you as well.

One can highly improve this answer by giving some results of studies on synthetic life.


How does one determine the sex ratio of a ZZ and ZW cross? In Campbell's Biology Chapter 14-15, Mendelian Genetics & The Chromosomal Basis of Inheritance, question 12 reads:

12) In birds, sex is determined by a ZW chromosome scheme. Males are ZZ and females are ZW. A recessive lethal allele that causes death of the embryo is sometimes present on the Z chromosome in pigeons. What would be the sex ratio in the offspring of a cross between a male that is heterozygous for the lethal allele and a normal female?

A) 2:1 male to female

B) 1:2 male to female

C) 1:1 male to female

D) 4:3 male to female

E) 3:1 male to female

The correct answer is A. In my Punnett square, there were two male and two female so shouldn't the answer be C?

Let $Z$ be the chromosome carrying the non-lethal dominant allele, and $Z_l$ the chromosome carrying the lethal recessive allele.
The Punnett square goes:

$Z_lW$ is not viable, so there are two possible male genotypes ($ZZ$ and $ZZ_l$) and only one possible female ($ZW$). So the correct answer is A. indeed.


Where does the term "cos site" come from? The word cosmid is derived from cos sites of lambda phages.

Why are cos sites called cos sites? What does this "cos" refer to?

"Cos" is the abbreviation of "cohesive end site". This is a speciality of the lambda phage which has to be linearized to fit into the phages head, but circularizes in the host cell. To achieve this, it has the cohesive (or sticky) sites at each end.
See here and also the publication by Allan Campbell on "Bacteriophages".


In a typical model ecosystem, what might the percentage of plants be to top predators and everything inbetween? I'm not sure if this will be a simple question that is almost a natural law for an ecologist, or a complex serious of assumptions.

I vaguely remember from school that only 10% of the energy is converted to biomass at each 'level up' however I have never seen any academic support of this. Lets say we have a fairly representative model ecosystem. In a pyramid of biomass, what percentage of biomass would I expect to see at each level (top predator, primary predator, herbivores, plant mass)?

An additional part I would like to know is does this ever correlate to the ecosystem of any given tier. i.e typically 5 predators will be found in the same area as 20 herbivores rather than 10% of predator biomass for 100% of prey.

There are plenty of diagrams available on google, but I have yet to see anything that looks credible. Any citations to academic sources would be greatly appreciated.

The percentage of biomass at each stage will vary tremendously, based on the following factors:

1: Relative turnover rate of the biomass. When biomass turnover is very high (for example in plankton and whales), it is possible for whale biomass to exceed that of the plankton, even through the whales feed on plankton. Therefore, it is better to use a pyramid of energy, where the total energy flux through a specific trophic level is used. See the article here for more detail.

  Just as with the inverted pyramid of numbers, in some rare exceptions, there could be an inverted pyramid of biomass, where the biomass of the lower trophic level is less than the biomass of the next higher trophic level. The oceans are such an exception because at any point in time the total amount of biomass in microscopic algae is small. Thus a pyramid of biomass for the oceans can appear inverted (see image part b). You should now ask "how can that be?" If the amount of energy in biomass at one level sets the limit of energy in biomass at the next level, as was the case with the hares and foxes, how can you have less energy at the lower trophic level? This is a good question, and can be answered by considering, as we discussed in the last lecture, the all important aspect of "time". Even though the biomass may be small, the RATE at which new biomass is produced may be very large. Thus over time it is the amount of new biomass that is produced, from whatever the standing stock of biomass might be, that is important for the next trophic level.

2: Biomass conversation rate in each trophic stage. For example, the article on entomophagy cites a number of papers that insects convert vegetation to biomass approximately 10 times more efficiently than cattle. A population of humans that fed on cattle would have a different biomass (and energy) pyramid than a population of humans that fed on locusts, for example.


What spider is this? Is this invasive or dangerous? Hi the picture below has been taken here,
I've never seen such a spider, is it an invasive specie or a dangerous one?

thank you

That appears to be a zebra jumping spider (Salticus scenicus). It is fairly widespread throughout North America. It does not post any kind of threat to people or to the environment:
Here is a map of iNaturalist observations for zebra jumping spiders.

And here is a gallery of photos you can view: https://inaturalist.ca/taxa/68901-Salticus-scenicus/browse_photos


Seeing new colours with new photoreceptors If we developed new "eyes" that could see "non-visible spectrum colours" and connected them to our brains, would our brain be capable of identifying and interpreting those new colours? Is our brain hardwired to only de-encode information about RGB using our SML cones?

How is color information transmitted from the eye to the brain?
Our brain receives the information as an FM signal, but does that mean a different "carrier frequency" is used in the FM will the brain detect and interpret this new colour?

Cerebral activity during exposure to non - visible light
We lack the ability to see colours outside of the visible-spectrum due to a lack of photoreceptors.

https://www.quora.com/Why-cant-we-think-of-a-new-colour-Is-it-really-impossible-to-think-of-any-colour-that-doesnt-exist-right-now-Is-the-light-spectrum-the-only-possible-source-for-new-colours-or-might-there-be-something-else Note that this link states we can "imagine" new colours in a pseudo kinda way.

The two points I found online providing information about my question: Yes adding new photoreceptors/sensors to our eyes could be a way to see new colours and yes sending a different signal would seem to be the way to interpret a new "colour". But those answers only partly apply to whether it's actually possible and only narrowly approach this question.

Each human optic nerve contains between 770,000 and 1.7 million nerve fibers, So it will be beyond human grasp to swap eyes in the near future, genetic eye and optic fiber development has to happen in the womb. Eye grafts require some kind of neural nanotechnology which is probably multiple generations away.

If you replace a human photoreceptor with another color, the result is: un-demonstrated/unknown.

Genetically engineered photoreceptor color swap (swap UV and blue)  which sends impulses to the same optic nerves as the previous color, may, and probably would work fine.

If you switch one eye to CMY and keep the other as RGB, it should have a usable result.

If you switch both eyes to CMY it's fine too, we would expect that there would be a fair vision perception, perhaps equivalent to RGB in clarity.

If you design a fetus with 4-5 photoreceptors and let it develop normally, It would have an unknown result. Perhaps the baby would have augmented vision, perhaps troubled. It's not know and many scientists would love to know the result.

I'd wager that a human with 4-5-6 colors of photoreceptors can be genetically engineered to see, within our lifetime.


What does 'H' in BamHI stand for? It's not explained on the wikipedia page. So if, apparently, 'H' is not relevant, why is it part of the name? And if it is relevant, why is it not explained?

These enzymes are named by the bacteria and the strain from which they are isolated. For BamHI this is Bacillus amyloliquefaciens strain H. In the beginning the enzyme was named BamI, which was later changed to BamHI.

See these two references:

Isolation of a sequence-specific endonuclease (BamI) from Bacillus
amyloliquefaciens H.
Recognition sequence of specific endonuclease BamH.I from Bacillus
amyloliquefaciens H.

The same is true for all the other restriction enzymes, so is EcoRI the first restriction endonuclease isolated from Escherichia coli strain R.


Benefits of CLARITY? What are the benefits of CLARITY over this technique that was published more than a year earlier?

Of course the second technique needs a fancier microscope that is likely more expensive and requires more technical ability. But CLARITY requires an objective with a very long working distance. I'm no expert in optics, but I'm pretty sure this results in a significant decrease in numerical aperture and therefore resolution.

It seems as though the other method is simply better than CLARITY, and that a lab serious about doing whole brain imaging could afford to invest in a setup similar to the one described. Yet this technique received none of hype that was bestowed on CLARITY. Am I missing something?

To start with, CLARITY is a whole-brain imaging technique , there is no need for sectioning which destroys connections and can cause the brain slices to warp as they are being cut. The costs for setting up CLARITY are much lower because all that is needed is chemicals to get the prep ready for imaging whereas in the Nat Methods paper you have to set up an automated slicing and imaging system,not an easy task by any means. Therefore an investigator is more likely to use CLARITY due to its easy of setting up and low start up costs. Also, as with any brain slice technique , you lose patterns of connectivity among neurons that are more than the slice distance apart(i.e in the next slice) and you don't look at the "whole picture". Thus due to the complexity,high start-up costs and specialized machinery STP is a poorer method than CLARITY for whole-brain imaging.As for resolution, I agree with you on principle that CLARITY has worse resolution(I looked through the paper but couldn't find exact figures) although you have to consider this in terms of all the trade-offs.


How to prevent a old promoter region from attaching onto a plasmid instead of a new one during ligation? What I am trying to do is take out a existing promoter region in a plasmid, and replace it with a new one. So first I use the appropriate restriction enzymes to get rid of the existing promoter region. Next, I add in the new promotor fragment which has the appropriate sticky ends, and then through ligation, I want to place the new promotor in the plasmid.

Since the old promotor region and new promotor region will have the same 'sticky ends', how do I prevent the old promotor region from getting placed into the plasmid instead of the new one during ligation?

Run it out on a gel after digestion  and extract the vector only.
Treat with a phosphatase after digestion. This will prevent religation since you need at least one of your fragments to be phosphorylated for the ligation to work.
(A must regardless) sequence several colonies at the end.

I recommend doing all three.

Edit: option 4: digest with a third enzyme that cuts in your old promoter but not the vector or the new promoter.


mRNA with Pseudouridine and 5-methylcytidine? I am making mRNA by in vitro transcription for transfection purposes. There is a lot of literature about how protein expression is increased and innate immune activation is decreased by substituting uridine for pseudouridine and cytidine for 5-methylcytidine. I decided to try this, but my yield was lower and the mRNA was shorter than when using natural nucleotides. The papers all say they made the mRNA by simply using the new nucleotides in their in vitro transcription kits, but they never mention any further changes to the protocol. Now I would assume that since pseudouridine and 5-methylcytidine are a little different from the normal substrates for RNA polymerase that they might not be incorporated as quickly and the resulting reaction rate would slow down. It might be possible that the Polyadenylate polymerase that adds the polyA tail doesn't recognize the modified mRNA as well. Both a slower reaction rate and less efficient tailing could make a lower yield of shorter mRNA.

Does anyone here have any experience with IVT using modified nucleotides and can suggest something to improve yields?

After a couple months I got this working. I ordered the psuedouridine and 5 methylcytidine from Trilink. I also switched from the mMessage mMachine kit the the Megascript kit. Megascript has all the nucleotides separated while mMessage mMachine has them pooled. You have to dissolve Trilink nucleotides so that the concentration is the same as the natural nucleotides in your IVT kit. Then you just use the non-natural nucleotides instead of UTP and CTP. Let the IVT reaction run 4 hours. Be careful about RNAse contamination.


What is it that specifically kills ALS patients? ALS is a fatal motor neuron disease, and even though there are many different articles out there on the topic "How does ALS actually kill you?", none of them really delve deep enough into biology to adequately answer the question.

For instance, many articles cite "respiratory failure", or "CO2 poisoning". But the last time I checked, ALS doesn't make your lungs explode or cause your body to start producing toxic levels of CO2. So obviously, we need another level of detail here to support these claims. I'd be willing to be that with "respiratory failure", either the neurons innervating the diaphragm break down (hence you become physically unable to draw air in and push CO2 out), or perhaps the tiny/micronic structures inside your alveoli become impaired for some reason. If the former, then why wouldn't a ventilator/respirator help the patient?

Either way, I'm interested in a biological/neurological explanation for why ALS is considered to be (ultimately) fatal.

TL;DR Ventilation assistance does help but there are other factors.

ALS is a degeneration of the motor neurons, replacing them with hard material (i.e. sclerosis). The neurons innervating the muscles involved in respiration deteriorate and so it becomes difficult to breath, swallow, cough, etc. There's a compounding effect: we know that blood O2 and CO2 levels are balanced by respiration, O2 in/CO2 out, and we know that swallowing/coughing clear secretions from the respiratory tract. Basically you end up with trouble oxygenating your blood and riding it of CO2, hence CO2 poisoning. This can result in what is known as type 2 respiratory failure, characterized by low oxygen and high carbon dioxide levels (hypoxemia and hypercapnia). Low secretion clearance in the lungs can also result in aspiration pneumonia in addition to poor gas exchange.

Ventilation methods such as BCV are capable of mechanically assisting breathing, and maintaining ventilation-perfusion state in a way that prevents respiratory failure, but unfortunately doesn't slow the progression of the disease. The problem then is that in, for example, particularly severe cases, the quality of life has to be taken into account because tongue movement, gross movement in general due to motor neuron degeneration just fails. This can lead to what is essentially locked-in syndrome (LIS), and clinical outcomes can widely vary, though in this article they report the more pleasant outcomes of patients experiencing LIS. I think that for these cases due to poor communicaton patient-reported outcomes are fairly underreported, but family and caregivers at this point have to take into serious consideration options such as euthanasia. Cutting off ventilation can result in type 1 or 2 respiratory failure.

Now, I lack actual data for this statement but I should also point out that not all patients receive the same care or opt for assisted ventilation, in which case late-stage ALS would invariably lead to total neurodegeneration to breathing muscle innervation, where assisted ventilation becomes a requirement for survival.


What kind of spider is this? Brown with white spots It was found in Houston, Texas, but I've never seen one before. Does anyone know what it is?

Sub-adult tropical orb weaver spider.  "Its range is largely circum-Caribbean, occurring in Florida, Louisiana, and Texas along the Gulf Coast of the United States."

Harmless to humans and considered beneficial.

  Bites of this species are not known to cause serious effects to humans. ... The web probably catches many moths and other night flying insects; these spiders may be particularly beneficial along woodland borders of field agroecosystems and within orchards.


Are domesticated animals really "more intelligent," or is that a myth/misunderstanding? Often do I hear people speaking of how the domestic house cats are more friendly, less ferocious, less savage-like, and smarter and/or than their distinct but equivalent feline-species friends, like lions, tigers, jaguars, panthers, leopards, cheetahs, etc. Is this provably true in any form or way?

Are domesticated animals really "smarter" or less ferocious, or are some simply, but assumption of lessened threat potential, more so inclined to deem the house cat/dog as less ferocious simply because it's not such a big threat? Look at it this way:

This little beast here is "very cute" because he/she is small and barely 9 lbs. When playing, he/she isn't directly threatening to many human's safety, and many people are not afraid of cats; however, is he/she really smarter because he/she is safer and less dangerous to us humans only?

This beast, however, is hundreds of pounds heavier and many feet longer. Is it considered more savage-like because it can seriously harm and possibly kill humans by playing a little rough, which is like how a 9 lb. house cat would play equivalently, but would give you some light scratches at worst.

I've also heard arguments about "friendliness" of felines, usually claiming that house cats are friendlier due to evolution and nurturing/upbringing; lions/tigers, on the other hand, are claimed to be naturally unfriendly and have "more wild" in the, and incapable of being as "friendly" or "trustworthy" as a house cat. Point is, I'm probably not the only person who's heard this. Also, consider other animals, like dogs.

Dogs come from the grey wolf, to put it simply. Compare both a typical house dog and a wild grey wolf, and it's pretty obvious that many would assume the house dog is safer, friendlier, and less harmful, despite the fact that some domesticated dog breeds can pack a greater bite than the wild grey wolf.

Comparing the house dog's behavior to the wild grey wolf is also not a good measure of "friendliness", as compare a savage Homo sapiens from an uncivilized territory to a common city person, and you'd think the same thing: that the savage human is "less intelligent" and the city person is more so.

Domestication has little, if anything, to do with intelligence.  From biologist Jared Diamond, the 6 criteria for domestication are as follows:

  Flexible diet – Creatures that are willing to consume a wide variety of food sources and can live off less cumulative food from the food pyramid (such as corn or wheat), particularly food that is not utilized by humans (such as grass and forage) are less expensive to keep in captivity. Carnivores by definition feed primarily or only on flesh, which requires the expenditure of many animals, though they may exploit sources of meat not utilized by humans, such as scraps and vermin.
  Reasonably fast growth rate – Fast maturity rate compared to the human life span allows breeding intervention and makes the animal useful within an acceptable duration of caretaking. Some large animals require many years before they reach a useful size.
  Ability to be bred in captivity – Creatures that are reluctant to breed when kept in captivity do not produce useful offspring, and instead are limited to capture in their wild state. Creatures such as the panda, antelope and giant forest hog are territorial when breeding and cannot be maintained in crowded enclosures in captivity.
  Pleasant disposition – Large creatures that are aggressive toward humans are dangerous to keep in captivity. The African buffalo has an unpredictable nature and is highly dangerous to humans; similarly, although the American bison is raised in enclosed ranges in the Western United States, it is much too dangerous to be regarded as truly domesticated. Although similar to the domesticated pig in many ways, Africa's warthog and bushpig are also dangerous in captivity.
  Temperament which makes it unlikely to panic – A creature with a nervous disposition is difficult to keep in captivity as it may attempt to flee whenever startled. The gazelle is very flighty and it has a powerful leap that allows it to escape an enclosed pen. Some animals, such as the domestic sheep, still have a strong tendency to panic when their flight zone is encroached upon. However, most sheep also show a flocking instinct, whereby they stay close together when pressed. Livestock with such an instinct may be herded by people and dogs.
  Modifiable social hierarchy – Social creatures whose herds occupy overlapping ranges and recognize a hierarchy of dominance can be raised to recognize a human as the pack leader.

From his Pulitzer prize-winning book.

We (as a species) domesticated animals (and plants) by selecting traits we sought, and then breeding to keep alive/emphasize these traits. In hunting animals (retrievers, for example), intelligence may be one of those traits. Others might include obedience, speed, agility, even dark-colored coats for camouflage.

It's not really correct to say "more evolved" as @MarchHo explains in his comment. Rather, you might say "more docile", or "less aggressive".

Keep in mind that less aggressive, domesticated animals are not necessarily more intelligent than their wild counterparts.

status-myth


Differences between Gradualism and Uniformitarianism From what I understand, gradualism is the idea that small changes affect species over time. Uniformitarianism argues that the same processes that occurred in the past are the same as those in the present.

Does gradualism state that these small changes are constant over time? In that case, it isn't much different from uniformitarianism.

I'm thinking that the difference that uniformitarianism allows for catastrophes and supports Aristotle's scala naturae, while gradualism makes a point for evolution due to its theory of slow processes.

Gradualism is the view that large-scale changes occurs by the accumulated effects of small changes over long periods of time, rather than by rare cataclysmic events of massive effect.

Uniformitarianism is the view that the same forces that shaped the world in the past continue to operate today. Historically, uniformitarianism has often included aspects of gradualism (i.e. definitions by Lyell), e.g. by assuming uniformity of rates. Uniformitarianism was also originally proposed as the opposite of Catastrophism. However, in modern use, the focus lies on uniformity of processes, and rapid catastrophic changes are allowed under uniformitarianism. Also note that the term Actualism is sometimes used for modern interpretations of uniformitarianism.

If we posited that early evolution occurred by small Lamarckian changes and current evolution occurs by small Darwinian changes, we have a model that is gradualist but not uniformitarian.

If we posited that the earth's topography was formed by meteor impacts and massive tsunamis, in sharp sudden strokes of massive effect, but acknowledged that these same processes occur today, we would have a theory that is uniformitarian but not gradualist.

(I don't understand what you are asking in your last paragraph, or how this relates to your main question.)


If the covid-19 appeared once, could it reappear anytime? Governments are imposing confinement measures on their populations, trusting that if there is no more transmission the virus will die out.
But since this coronavirus appeared a first time, what could prevent it from reappearing any number of times ?

Frame challenge answer: you are jumping to the conclusion that they really hope the virus will "die out". But it's more likely they adopted those measures to slow its progression to a manageable degree. See e.g. this conceptual image from ECDC

Even if there are new outbreaks of COVID-19 in the future, when they happen is not irrelevant, as we could be much better prepared given the current/ongoing research on both (antiviral) treatments and possibly a vaccine as well.

Regarding the "meat" of the question, it's a matter of probabilities, not certainties. It was and is generally assumed that other [bat etc.] coronaviruses will jump hosts to humans in the future.

Besides SARS, another (much) lesser known cross-species jump actually occurred in China in 2016 with SADS-CoV, which killed thousands of pig[let]s, but was not infectious to humans. Annoyingly enough for the Chinese pig farmers, SADS-CoV re-emerged in early 2019 despite the fact that there were no cases reported between May 2017 and January 2019.


How should I ship plasmids? I shipped 10 µL of my vector miniprep to a collaborator in a 1.5 mL eppendorf parafilmed shut and stuffed into a 50 mL conical with some paper-towel padding.  However, something happened on the way and there was nothing (no liquid) in the tube when it arrived.  They didn't make any comments about the microcentrifuge tube popping open or broken parafilm, so nothing crazy happened but something did.

What's the most reliable way to ship plasmids?

A quite safe way of shipping plasmids is to put them on filter paper (see protocol and send a letter. Much cheaper.


Protein-protein interactions search I used STRING db in order to find all the interactions of the precursor protein APP. What I specifically need is a confirmation (supported by some article and experiments in it). But significant amount of interactors have only "Database" confirmation (mostly relaying on Reactome and KEGG data). Searching in these db's gives me neither article nor even the presence of these proteins in one pathway (what's weird). How can I obtain the data?
Thanks in advance!

You can try to use IntAct Molecular Interaction Database. The data in this database is based on:

data from the literature or from direct data depositions by expert
curators
<300k binary interactions in 2011  developed by the EBI's
Proteomics Services Team
recent reference: Aranda et al. '10

This is also mentioned in the summary of the Aranda et al.'10 article:

  IntAct is an open-source, open data molecular interaction database and
  toolkit. Data is abstracted from the literature or from direct data
  depositions by expert curators following a deep annotation model
  providing a high level of detail. As of September 2009, IntAct
  contains over 200.000 curated binary interaction evidences. In
  response to the growing data volume and user requests, IntAct now
  provides a two-tiered view of the interaction data. The search
  interface allows the user to iteratively develop complex queries,
  exploiting the detailed annotation with hierarchical controlled
  vocabularies. Results are provided at any stage in a simplified,
  tabular view. Specialized views then allows 'zooming in' on the full
  annotation of interactions, interactors and their properties. IntAct
  source code and data are freely available

Further you can use the Evidence tab in String(I assume you have already tried this but in the case you did not):

You can then click on Experiments, then something like this will show up:

You can see how (e.g. Reconstituted Complex assay) and you can see from which article this interaction is coming from if you click on an item in the table:


Are there any forms of heart failure where cell size decreases? I think hypertrophy happens in most of the cases. However, I am not sure if hypertrophy always happens. I started to think about wet lungs (pulmonary reason for the left-sided heart failure).

Can the decrease of cell size occur in the heart failure?

Literature covers only hypertrophy of the heart.
Atrophy not mentioned.

Theoretically atrophy of the heart would require some factors

mutations (which can destroy the gene to build up the organ),
poor nourishment,
poor circulation,
loss of hormonal support,
loss of nerve supply to the target organ,
excessive amount of apoptosis of cells, and
disuse or lack of exercise or disease intrinsic to the tissue itself.

Atrophy can happen locally in some part of the heart only, like in some parts of myocardial infarction.
However, the surrounding healthy tissue then undergoes hypertrophy so the total heart undergoes hypertrophy.
Some discussion about Cardiac atrophy here.


What proportion of the people who lived 1000 years ago have genetic descendants alive today? For context, I've been wondering about this for a paper I'm writing (in philosophy). Really, I want to figure out the chances that someone alive today will end up still having descendants 1000 years in the future. But people from 1000 years ago should be a good approximation.

So, any ideas? And are there any published papers which talk about this?

Expanding on @heracho's answer and Wikipedia, assume pi denotes the probability of having (exactly) i children, and that dm denotes the probability of extinction by the mth generation (note that this includes extinctions by all generations n with n < m). Then dm can be expressed as:

$\displaystyle d_m = p_0 + p_1 d_{m-1} + p_2 d_{m-1}^2 + p_3 d_{m-1}^3 + \dots = \sum_{i=0}^\infty p_i d_{m-1}^i$

with d0 = 0.

In other words, the probability of going extinct by the mth generation is equal to the probability of i children going extinct in m – 1 generations, summed over i. (The child lineages are assumed independent.) This recurrence relation allows you to calculate the extinction (and, by extension, survival) probability at any desired number of generations, if the values of pi are known. In simple cases it is also possible to work out the asymptotic value of dm by solving the fixed point equation dm = dm – 1 (see the Wikipedia page for an example).

In relation to your specific application, we can assume roughly 40 generations and use some empirical estimates of pi. The parity distribution of Denmark is given by Frejka (2008) as p0 = 0.127, p1 = 0.179, p2 = 0.443, p3 = 0.251 (where I simplify by assuming that people who have strictly more than 3 children actually have only 3 children). Plugging these parameters into the recurrence relation and iterating for 40 generations (see R code below), we get d40 = 0.17. Thus some 83% of the population can be assumed to have descendants in 1000 years.

I have taken Denmark as an example simply because it is the first country mentioned in Table 2 of Frejka (2008). However, to illustrate the dependence of the asymptotic value of dm on the parity parameters consider the case of Italy. From the same publication, we find p0 = 0.240, p1 = 0.235, p2 = 0.369, p3 = 0.156. With these values, we compute d40 = 0.41, obviously a very different situation.

I am not a mathematician, nor a biologist (nor a demographer), and the above logic obviously employs many ridiculous simplifications. It would be very interesting to know how all this pans out in a more realistic model.

Reference

Frejka, Tomas (2008) Parity distribution and completed family size in Europe: Incipient decline of the two-child family model? Demographic Research, 19(4): 47–72. https://www.demographic-research.org/volumes/vol19/4/19-4.pdf

R code

# get extinction probability (d) in generation m, given extinction
# probability in generation m-1, conditioned on probabilities
# of having 0, 1, 2, ... children (vector p)
extinctionprob <- function(d, p) {
  d <- d^(0:(length(p)-1))
  sum(d*p)
}

# iterate for 'ngen' generations
iterate <- function(ngen, p) {
  d <- 0
  for (i in 1:ngen) d <- extinctionprob(d, p)
  d
}

# usage example:
# iterate(ngen=40, p=c(0.240, 0.235, 0.369, 0.156))


How does stimulus reach neural threshold? I understand that when the stimulus into a neuron is greater than the threshold it triggers the action potential. Do all the contributing stimulus have to occur at the same time, or can they occur over time?

If neurons A and B connect to C, and C needs both A & B to activate to reach the threshold; can A fire first, then B - or do they both need to fire simultaneously?

If they can contribute towards the threshold over time then is there a decay that eventually returns the neuron to resting potential?

There is temporal summation of the stimuli. This is modeled in the Hodgkin and Huxley model .

To imagine the whole process, you should know that in the dendrites of the neuron, electric impulses are propagating passively ( the strength of the stimuli is decreasing over distance and time), in the axon the electric impulse is active ( in the form of action potential(AP) ).

Let me explain your second question with the help of mathematics:

Let's assume that T is the threshold value.

Func(x, t) is a function of the stimuli, where the depolarizing effect is decreasing with time and distance:

Func(A, t) > Func(A, t+1)

So after your assumption:

Func(A, 0) + Func(B, 0) = T

If we don't take into account temporal summation, in other words, if we are looking at only just one phase of the time, and A and B stimuli are not simultaneous, and in t=0, then there will be no AP.

Func(A, t1) + Func(B, t2) < T , where t1 != t2

But with temporal summation we can add previous stimuli into the equation. For example:

From the previous asyncronous stimuli, we got our two decreasing depolarizing factors, and over time we got one more stimulus from A, then with temporal summation they CAN produce an AP.

Func(A, t1) + Func(B, t2) + Func(A, 0) >= T,
if Func(A, t1) + Func(B, t2) >= Func(B, 0)

So after a depolarizing effect, the neuron enters into a hyperpolarized state and most of the sodium channels are inactive. This is called the refractory period. This is when, even A and B is applied simultaneously there will be no AP. And after the membrane potential gets back to his resting potential, then the whole process (including the temporospatial summation) starts from the beginning.


What species are these baby birds? I'm trying to save these baby birds' lives, and I need to know their species so that I can know how/what to feed them. Please help me ASAP .

If you are in Europe they are juvenile common swift (Apus apus).

There is a website dedicated to them, with a page on how to raise them: http://www.commonswift.org/Hand_rearing_Swifts.html

They are very fragile and with the wrong diet they might develop feather deformations. They also require a continuous effort because they eat very often. I raised them a couple of times and when they take off is magnificent but it is easy to do something wrong. If you have some recovery center or expert nearby  I suggest to hand them over.


What is cytoplasmic localization? I was studying development of chick but didn't understand what is cytoplasmic localization. My book says:

  After third cleavage , the rest of the cleavages are irregular and completely delimited cells are formed all over the germinal disc which is termed as blastoderm. This outcome of cleavage called cytoplasmic localization helps seal the developmental fate of each cell's descendants.

"Cytoplasmic localization" is a very general term and it means that something is present in the cytoplasm. For instance (hypothetical but there are known examples), you can say protein-X is localized to cytoplasm or the cytoplasmic localization of protein-Y is reduced upon phosphorylation. Similarly, there are terms like "nuclear localization", "ER localization", "mitochondrial localization" etc.

The usage mentioned in your excerpt is actually unclear and misleading. There is no process called cytoplasmic localization. What it actually means is that there are proteins/RNA inside the cytoplasm of the embryo that are asymmetrically distributed. When the cell divides, these molecules are therefore asymmetrically sorted to the daughter cells. Depending on what (and how much of) molecules the daughter cells receive, different cells adopt different phenotypes. Also note that the axis of division also plays a role; if lets say the distribution of a given molecule is asymmetric only about the anteroposterior axis and the division happens along that axis then both daughter cells receive the same amount of molecule and both the cells would be similar (w.r.t that molecule). This won't be the case if the division is along left-right axis. See the figure below.

  From: Berika et al., 2014

I am not sure which book you are following but Developmental Biology by Scott F Gilbert is a good book and explains these processes nicely.


Are plants really oxygen neutral? This accepted and most upvoted answer to the question Does grass alone produce enough oxygen for life? claims that plants are oxygen neutral:

  Plants are oxygen neutral The question wording is a bit misleading, as
  – surprise – plants do not produce oxygen. They produce oxygen only as
  long as they are growing, binding carbon in its mass. In long term all
  plants are oxygen neutral, as all oxygen which is created by them is
  again consumed when they dissolve, burn or are eaten, as carbon stored
  in them reacts with oxygen back to CO2. The more correct view how to
  describe this is not that plants produce oxygen, but that they store
  carbon.

I realize that a huge portion of our atmosphere's oxygen was produced by Phytoplankton, but the idea that plants produce zero net oxygen seems absurd to me. Is the information provided by that answer scientifically accurate? Please explain.

Plants are oxygen generators. Plants plus decomposition (i.e. the whole system, plants plus bacteria and fungi and fire and cows and termites) are oxygen neutral. So the statement is literally wrong, but may be functionally correct in the current environment.


What is this nighttime creature? I almost stepped on this little critter. It blended into my garage floor. It is about about the size of my hand, with huge bulbous eyes that immediately caught my attention. There was a distinct white bump below\between the eyes.  It froze when I turned on the light and did not move at all until I turned the light off. Then it moved faster than my eyes could follow in the direction of my garden.
I am on an island in the San Francisco Bay, California. The current temperature is ranging from 50 (night) to 65 degrees and rainy season has just started (late this year). It blended so well with the garage floor that my camera had problems focusing on it.

I believe this is an Arboreal Salamander (Aneides lugubris).
http://www.californiaherps.com/identification/bayareaherps.html#Lizards
http://www.californiaherps.com/salamanders/images/alugubrisbr1108.jpg


What is an Ihh-/- mouse? This one is too basic question:

I just came across $Ihh^{-/-}\ $ mouse. Is that means this mouse devoid of that gene Ihh. What is this sign called and are there other such representations?

The IHH gene encodes the Indian hedgehog homolog protein, a member of the family of hedgehog proteins that  regulates bone formation. The ihh-/- notation represents an animal which is homozygous for a null mutation in the gene (i.e. the animal has no functional IHH gene).


Is this an eastern hemlock (Tsuga canadensis) seedling? I recently planted a few seeds gathered from a Tsuga canadensis cone in soil gathered from a garden full of weeds. I can't tell if what I have growing is a hemlock seedling or just another weed. See photo:

No, this is not a Tsuga canadensis seedling.

A hemlock seedling should look something like this:

http://www.uky.edu/hort/propagation-canadian-hemlock


is this a brown recluse spider? What kind of spider is this? SE Michigan, light brown color, second picture less focused but w tape measure for scale. Thank you!

No, this is not a Brown Recluse.  There are several reasons for saying that, among them the fact that it's outside; it's hanging on a screen, and it doesn't look at all like a Brown Recluse - (Recluses don't have a rectangular cephalothorax "head end", and they have a bulbous abdomen, not that pointy-ended one this spider has).
As for what it is, there are some good clues - first that rectangular-looking cephalothporax.  That's pretty unusual in spiders, although it's not actually rectangular; it's just the central dark pattern is very blocky.  Then, look at that color - kind of a creamy light mahogany rather than a real brown, and no darker/lighter patterns that the bigger wandering spiders that look like this would have.  Finally, look how it's holding its legs - both the front pairs are close together.  That's something you tend to see in two sorts of spiders - the big Argiope orbweavers, and the big Fishing Spiders and their relatives.  Argiopes have a different body shape, pattern and color than this, and it would be a little unusual to find one this size hanging around not in a web.  Fishing Spiders are generally dark-colored, and with more patterning than this, but there is a close relative that fits this image:  the Nursery-web Spider, Pisaurina mira.  Here's the Bug Guide page, and a representative photo:

https://bugguide.net/node/view/2919


Deduce length order of 4 decapeptides based on the Ramachandran plot I have stumbled upon the following past exam question:

  4 decapeptides A, B, C, D, made only of glycine residues, have
  different conformations, and the phi and psi angles of individual
  peptides are indicated on the Ramachandran plot (unfortunately I
  cannot provide a specific plot). Order these peptides by decreasing
  length.

How should I solve this, what information useful in solving this problem can I deduce from the Ramachandran plot?

When φ = ψ = 180° the peptide is in the fully extended conformation i.e. it is the 'longest' it can be.

If it isn't possible to deduce a length order based on this information then I guess you will have to do some geometry to calculate the sums of the distances between the α C atoms using the known values for all of the bond angles - sounds laborious to me!

This site tabulates values of φ/ψ for typical structures (helix, sheet, turn) so it may be possible to decide if some of peptides are adopting these.


Is there a statistical analysis test I can perform that will give me a estimate of total population from my own smaller data sets? Doing my dissertation on the long term trends in moth populations. I am looking at the trends of specific species. Is there a method to obtain an estimate of total population from smaller samples?

I'm assuming you're asking how to estimate population size based on numbers of individuals you capture. Yes, there are many approaches to this. The R library SPECIES-R offers a number of methods of calculating this. They are described in the manuscript SPECIES: An R Package for Species Richness Estimation. Some of the methods described are:

Chao, A. (1984), Nonparametric Estimation of the Number of Classes in a Population, Scandinavian Journal of Statistics, 11, 265-270.
Norris, J. L. I., and Pollock, K. H.(1998), Non-Parametric MLE for Poisson Species Abundance Models Allowing for Heterogeneity Between Species, Environmental and Ecological Statistics, 5, 391-402.
Chao, A., and Bunge, J. (2002), Estimating the Number of Species in a Stochastic Abundance Model, Biometrics, 58, 531-539.

and many more.


What is "irrational" drug/molecule design? Both the papers "Directed evolution: the 'rational' basis for 'irrational' design" by Tobin et al. and "Rational and 'Irrational' Design of Proteins and Their Use in Biotechnology" by Nixon et al. reference the concept of "irrational" drug design, but never formally define it in their text.
Is there a formal definition of what makes a drug design process "irrational"? What is the meaning of the term "irrational" in this context?

Nixon AE, Firestine SM. Rational and "irrational" design of proteins and their use in biotechnology. IUBMB Life. 2000;49(3):181-187.
Tobin MB, Gustafsson C, Huisman GW. Directed evolution: the 'rational' basis for 'irrational' design. Curr Opin Struct Biol. 2000;10(4):421-427.

"Irrational" design in these papers refers to combinatorial mutagenesis, which is put forward as the alternative to "rational" protein design.

Rational design involves using existing information about a protein to choose residues to mutate.

From Nixon et al.:

  Alteration of function by rational approaches can be achieved through single-point mutation, exchange of elements of secondary structure, exchange of whole domains, or generation of fusion proteins

Whereas irrational design uses random mutations to gain insight into the functional capacity of specific residues or domains, which may then be further manipulated by rational approaches.

From Tobin et al.:

  ‘Irrational’ protein design using directed evolution methods relying on entirely random mutagenesis techniques has also had its successes, particularly in cases in which sequential rounds of mutagenesis have been pursued.


Is homosexuality an adaptation in humans? Homo sapiens have menopause - as some other mammals (e.g. some Cetacea) - a phenomenon where older females live for decades after the end of their own reproduction.

Perhaps homosexuality, that looks to hold at 10% levels in any population, may be just the same sort of adaptation?

Barnard's wonderful text "Animal Behavior: Mechanism, Development, Function and Evolution" offers some enlightening summary to the discussion of homosexuality in a biological context!

Brief Summary to ch 12, page 606:

  What we know so far:

  homosexual behavior is recorded all throughout animal kingdom
  there are evidence for genetic basis to homosexuality in various species including humans

  Three interrelated schools of thoughts:

  Homosexuality is maladaptive - external stress creates homosexuality

  reduce resource stress on family unit, youngest child tend to be gay (E.M. Miller 2000)
  *** mitochondrial DNA carries male killing genes, with male being a dead-end (Hurst 1991)

  Homosexuality as an adaptive early phase of development - homosexual acts are just target practice

  homosexuality is just males practicing sex on each other, most homosexual acts are performed by bisexuals with just as high fertility
  as straight males (Baker & Bellis 1995)

  Homosexuality advantages in other aspects of reproduction - homosexuality may imply better parenting

  homosexual genes induces feminine attributes in males such as sensitivity, empathy and kindness hereby increasing likelihood of long
  term pair bonding and paternal care (E.M. Miller 2000)

*** original text:

  A completely different suggestion is that homosexuality may reflect
  the interests of selfish genetic elements (see 2.4.3.2) inherited
  maternally on mitochondrial DNA for which males are effectively a dead
  end. Some insects have been shown to carry 'male-killing' genes on
  their mitochondrial DNA, so perhaps homosexuality is a similar, if
  more benign, rout to sidelining males (Hurst 1991)


Is there any checked case of "involution"? I know that strictly speaking the term "involution" referring to the evolution theory doesn't hold any meaning. Organisms keep on evolving and changing with time, that's all.

But the following situation could perfectly happen:

Some event causes some organisms to evolve certain characteristics that allow for a better survival, but with time that event stops and what was previously and advantage for these organisms, now it's a disadvantange, and to adapt to the new situation what they do is to exactly remove these characteristics and they end up being exactly the same as they were previously to the change. It could be considered that they have "involutioned".

Are there checked examples of this? (Not just as theory, examples of organisms where this "involution" has been observed). I'm specially interested in "complex" organisms, I think this is not that far fetched to happen to organisms like bacteria, virus or the like. But for more "complex" organisms I guess it's too much of a coincidence.

Edit: I'm putting an example to clarify:

Let's imagine we have a huge amount of plants of the same species which can grow extremely fast (in the way they could simulate 100000 years in evolution in one hour) and we have an atmosphere for them that is the same as current one. (Not realistic, but let's make the thought experiment). We also put some put of these plants apart.

Little by little we go changing all the carbon dioxide in that atmosphere with something, like, for example, nitrogen, it's to expect, that, with time, some plants will appear to better use the nitrogen, at least up to the point where they can survive, as carbon dioxide is every time lower and lower and plants not adapted to this end up dying.

When we finally have only nitrogen processing plants we start the opposite, we start filling little by little with carbon dioxide, it's to expect that the contrary would happen.

Now, if a biologist were to observe the plants that were set apart at the beginning and the new created plants he wouldn't be able to tell where each plant is from, unless he was aware they were separated to do the experiment.

"Exactly the same" probably doesn't fly, just because there is so much possible variation, but for a fairly obvious example, consider birds.  Their ancestors evolved flight: some modern-day birds (ostriches, emus, kiwis, &c) have lost that ability, though their vestigal wings haven't re-evolved into legs.  But consider the evolutionary link between birds and theropod dinosaurs, and how many of those (e.g. T. rex) had vestigal forelimbs.

Another example would be dolphins and ichthyosaurs, which both independently "involved" from land-dwelling creatures back to a form that's similar to the ancestral fish.

But of course neither of these are really "involution" in the sense of reversing an evolutionary path.  They are cases of organisms exploring new evolutionary paths, where the environmental pressures (such as need for streamlining to move efficiently in water) cause them to resemble some ancestral form.


Relieving pain by massage How come the pain in our body, primarily due to excessive physical exercises, vanishes after having a massage? What is the mechanism?

Short Answer
What you're referring to is called Delayed Onset Muscle Soreness (DOMS).
We don't really know what causes DOMS, but it's most likely caused by a cascade effect started my muscle injury. Also, we aren't sure if massages (or what type of massages) really help relieve the pain.

What is Delayed Onset Muscle Soreness (DOMS)?
Delayed onset muscle soreness (DOMS) is the sensation of muscular discomfort and pain during active contractions that occur 24–48 h after strenuous exercise. The initial symptoms are most evident at the muscle-tendon junction and thereafter spread throughout the entire muscle.(ref)
Physiopathology of DOMS
The mechanism is not completely understood and several theories have been proposed, namely: (ref)

lactic acid
muscle spasm
connective tissue damage
muscle damage
inflammation
enzyme efflux

The underlying cause is probably a conjunction of 2 or more of these theories. However, ultimately, the underlying transversal cause is muscle microtrauma. There are a few interesting findings that support this:

High-intensity eccentric contractions induce performance decrements and DOMS (ref),(ref)

Concentric exercises seems to cause no soreness (ref)

Eccentric contractions are high force and are associated with muscle damage (ref)

Creatinine, Potassium(K) (and sometimes Myoglobin) excretion (urine levels) and Creatine Kinase(CK), K and Neutrophil levels in blood are increased after intense exercise. This is also seen in acute rhabdomyolysis, a condition in which damaged skeletal muscle tissue breaks down. (Ref: Harrison's Principles of Internal Medicine, 17th Ed, Chapter 273: Acute Renal Failure)

The effects of massage on DOMS
A massage MAY indeed reduce pain in DOMS (ref), however, most studies' results are inconsistent and hindered by methodological flaws(ref) such as lack of control of the placebo effect or the subjectivity of pain.
A study by Smith et al suggests that sports massage will reduce DOMS when administered
2 hours after the termination of eccentric exercise. They also found lower CK levels, higher cortisol levels and a prolonged elevation of neutrophils in the blood of massaged groups (ref). This might mean lower muscle trauma and inflammation due to a reduced migration of neutrophils (to the muscle) and higher levels of serum cortisol.
The increment in the blood flow to the muscles during a massage might also be implicated in the process, by restoring oxygen and nutrients required to muscle remodeling. However, there is no clinical evidence of this fact and a study strongly rebutes this (ref)
Hyperstimulation of the nerve endings in the affected muscles might give a sense of pain relief, in a context of microtrauma. (ref)