Tuesday, 29 May 2007

Is cell membrane living - Biology

It is neither living nor dead. It is simply not alive the way that any other collection of chemicals is not alive. Is salt alive or dead?



A cell's membrane consists of a collection of chemicals (mainly lipids and proteins). Individual chemicals can never be considered living or dead, any more than rocks or water can be living or dead. While the actual definition of life is tricky, everyone agrees that in order to be alive you need to (at the very least)



  1. Somehow interact with your environment

  2. Be able to make more copies of yourself

Therefore, the cells themselves are alive but the individual parts of the cells are not since they cannot make copies of themselves (this gets complicated when considering some organelles but never mind that here). Similarly, you are alive but your teeth are not. While you can make more of you (you can have children) your teeth cannot make more teeth.

pharmacology - How do Benzodiazepines induce Rewarding (Euphoric) effects?

Okay, I read the question wrong.



Benzodiazepines do not bind to GABAA receptors universally. Thus the presumption that it inhibits the mesolimbic dopamine pathway may be wrong. They may not interact directly with said pathway at all.



Many subtypes for the GABAA receptor exist. The receptor consists of 5 subunits. The following subunits are known to exist: α1-6, β1-3 and γ1-3. The most common combination has two α, two β and one γ. You find ones with distinct compositions at distinct locations in the brain. All have two bindingsites for GABA, but only a subset has an additional binding site for benzodiazepines.



The benzodiazepine binding site is at the interface of an α and a γ subunit, so receptors without this structure will show no affinity for benzodiazepines. Additionally the α subunit must contain a histidine residue, which is only true for α1, α2, α3 and α5. That is paraphrased from wikipedia, where you can find the sources as well.



I still think you need to consider the idea that benzodiazepines may not interact directly with the dopaminergic reward pathway, like opiates and cocaine does. I attribute the euphoria to be an indirect effect, resulting from the muscle relaxation (which will feel like you had a good massage), and the calmness of the mind.

Sunday, 27 May 2007

evolution - Why can't we propose a solid theory regarding origin of life?

First of all, we do have some solid theories to explain the origin of life. That said, the main thing missing in order to be able to accept one of these theories with a decent amount of certainty is the ability to run a planetary scale experiment for a few billion years.



The theories are fine, the problem is that we cannot really test them. In order to test a theory that describes the origin of life, we will have to recreate the original conditions (think of a test tube the size of the Earth) and then pump energy into the system and watch what happens over the next few billions of years. This is not really feasible, for obvious reasons. I really doubt you will be able to get funding for an experiment that will run that long.

Thursday, 24 May 2007

molecular biology - How to secrete a recombinant protein from E. coli?

According to the 2012 iGEM Kyoto team:




The Twin Arginate Translocation pathway(TAT) is [an endogenous] secretion system in E.coli. This system can carry proteins that have torA signal amino acid sequences at N terminal. TatA, TatB, TatC and TatD compose Tat complex on inner membrane. Tat complex recognizes torA signal peptide and then it transports protein (with torA) from cytoplasm to periplasm. In addition, protein that has passed through TAT pathway cut off the torA signal. Proteins which are secreted by this system have no tag that obstruct the activation of the protein.




The team created a cassette with the TAT genes to increase the expression of the pathway and also included the Kil gene, which perforates the outer membrane, possibly aiding the external diffusion of the secreted protein. They noted, rather tongue-in-cheek, that




Needless to say, function of outer membrane as membrane is essential for E.coli to survive. In other words, overexpression of Kil causes cell death. In this reason, we must find suitable amount of expression.




Note: according to their lab notebook, the team never observed extracellular GFP via confocal microscope (search that page for 'confocal'). So. Beware :)



Their project page also includes some references to the following literature:



  • Tracy Palmer and Ben C. Berks "The twin-arginine translocation (Tat) protein export pathway"

  • J. H. Choi. S. Y. Lee "Secretory and extracellular production of recombinant proteins using Escherichia coli"

  • G. Miksch · E. Fiedler · P. Dobrowolski · K. Friehs "The kil gene of the ColE1 plasmid of Escherichia coli controlled by a growth-phase-dependent promoter mediates the secretion of a heterologous periplasmic protein during the stationary phase"

  • Brad A. Seibel* and Patrick J. Walsh "Trimethylamine oxide accumulation in marine animals: relationship to acylglycerol storage"

senescence - What reasons allow for women to outlive men?

In a study on longevity in 121 countries, women tended to outlive men by about 5 years [1]. The suggested causes for this are numerous, some of which are temporally, geographically, or culturally specific.



On the terminology, sex tends to refer to the absolute biological differences, whereas gender relates more to differences in perception/lifestyle (for instance, socio-economic differences).



Evidence



In a study on Greek centenarians the authors found that women outnumbered men (1.68:1), with men having a higher likelihood of smoking, and thus are more at risk of smoking-related illness and mortality (historically this was more true than today) [2]. This is also true for alcohol consumption. The authors also report that having a first degree relative who was also a centenarian is associated with longevity (highlighting the importance of genetic factors in lifespan determination).



There is also evidence that the rate of telomere shortening (number of cell-divisions until cell-cycle arrest) is sex-specific [3].



rwst cites an interesting paper, that presents evidence that suggests male hormones may decrease lifespan [4]. This may be due to differential onset of atherosclerosis and cardiovascular disease, caused by exposure to different sex hormones [5].



In a review on the brain/behaviour specific aspects of differential ageing between the sexes, the authors discuss differences in brain anatomy and cognitive (and emotional) functionality between the sexes [6].



Remarks



This is by no means an exhaustive list of the reasons for differences in lifespan between the sexes in humans. There are likely to be many other causes, such as men tending to have more 'risky' behaviours, and possibly other unknown genetic effects, such as having 2 X chromosomes, vs. XY.



References



  1. Møller, A. P., et al (2009). Why men have shorter lives than women: effects of resource availability, infectious disease, and senescence. American journal of human biology : the official journal of the Human Biology Council, 21(3), 357-64. doi:10.1002/ajhb.20879

  2. Tigani, X., et al (2011). Gender differences in Greek centenarians. A cross-sectional nation-wide study, examining multiple socio-demographic and personality factors and health locus of control. BMC geriatrics, 11, 87. doi:10.1186/1471-2318-11-87

  3. Barrett, E. L. B., & Richardson, D. S. (2011). Sex differences in telomeres and lifespan. Aging cell, 10(6), 913-21. doi:10.1111/j.1474-9726.2011.00741.x

  4. Min, K.-J., et al (2012). The lifespan of Korean eunuchs. Current Biology, *22(18), R792-R793. doi:10.1016/j.cub.2012.06.036

  5. Pérez-López, F. R., et al (2010). Gender differences in cardiovascular disease: hormonal and biochemical influences. Reproductive sciences (Thousand Oaks, Calif.), 17(6), 511-31. doi:10.1177/1933719110367829

  6. Kryspin-Exner, I., et al (2011). Geropsychology: the gender gap in human aging--a mini-review. Gerontology, 57(6), 539-48. doi:10.1159/000323154


Update



Just been reading this interesting paper by Maklakov, et al (2013, BioEssays) titled "Evolution of sex differences in lifespan and aging: Causes and constraints", which presents a more evolutionary/genetic argument for the differences.



Abstract



Why do the two sexes have different lifespans and rates of aging? Two hypotheses based on asymmetric inheritance of sex chromosomes (“unguarded X”) or mitochondrial genomes (“mother's curse”) explain sex differences in lifespan as sex-specific maladaptation leading to increased mortality in the shorter-lived sex. While asymmetric inheritance hypotheses equate long life with high fitness, considerable empirical evidence suggests that sexes resolve the fundamental tradeoff between reproduction and survival differently resulting in sex-specific optima for lifespan. However, selection for sex-specific values in life-history traits is constrained by intersexual genetic correlations resulting in intra-locus sexual conflict over optimal lifespan. The available data suggest that the evolution of sexual dimorphism only partially resolves these conflicts. Sexual conflict over optimal trait values, which has been demonstrated in model organisms and in humans, is likely to play a key role in shaping the evolution of lifespan, as well as in maintaining genetic variation for sex-specific diseases.

Wednesday, 23 May 2007

bioinformatics - ChIP-seq and the output of SPP

I have been processing some ChIP-seq data with the R package spp. I looked through the literature (ENCODE uses it) and it seemed that spp is indicated as a good program to use. I have found and adapted the two tutorials I found for using spp (first and second), and read the original paper. I have also e-mailed Prof. Karchencko and posted on the bioconductor listserv - all with no response. My question is about the MSER and the predicted sequencing depth - additional output of spp. So what I think the MSER is, is the score value above which a peak is authoritatively determined? When I look at peaks above this score value they are very well defined. Also, is the predicted sequencing depth is a prediction of the number of additional "tags" necessary so that the MSER and the FDR value coincide? It is hard to find decent information about this program. Any advice or additional information is greatly appreciated!



TIA

Tuesday, 22 May 2007

terminology - What does "Activation" refer to in the context of the symptoms of Schizophrenia and Schizoaffective Disorder?

The authors use the Positive and Negative Syndrome Scale (PANSS) to assess symptoms. One of its cluster scores is activation factor.



Summary:
http://en.wikipedia.org/wiki/Positive_and_Negative_Syndrome_Scale



Original publication of the article, which doesn't list activation factors:
http://schizophreniabulletin.oxfordjournals.org/content/13/2/261.long



Marketed currently here:
http://www.mhs.com/product.aspx?gr=cli&id=overview&prod=panss



None of the sources I saw specified what is meant by activation factor, and many didn't even mention it. It's possible that it's the hyperactivity mentioned in the original publication. Also, it's possible that it's a modified category in the version sold at the last link. Hopefully this is enough information to get you started, if you want to hunt down the details.

Thursday, 17 May 2007

human biology - HSL Lightness vs Eye sensitivity

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:



  1. 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 $\gamma = 2.2$: $f(C) = C^{2.2}$.


  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.)


  3. 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.)


Wednesday, 16 May 2007

neuroscience - If a non-mammal is starved of oxygen for some time, how long would it take the animal's neurons to die?

Medically, recovery of brain function after 3 minutes of oxygen deprivation at body temperature is rare.



Further down here in 1 it indicates that at lower temperatures the time can be much longer. At 13C, the record is 80 minutes for people. Animals cooled to 0C have a record of recovery of three hours! Not sure how much like themselves they feel after that though...

Tuesday, 15 May 2007

botany - Any food crops that could grow in a desert provided that they get fertilizer and water

I am working on an idea to provide nearly unlimited amounts of water in desert regions. To make this commercially viable. I would use the water to irrigate desert sand and grow crops. Given my extremely limited understanding of biology, I cannot find an answer to the following question:



Are there any food crops (preferably high valuable/low maintenance ones), that can grow in a desert, given that I can just provide the seed, water and fertilizer and stop sandstorms.



My motivation for investigating this is the following map showing regions that are either already deserts or at risk of becoming deserts:
enter image description here



Source: http://en.wikipedia.org/wiki/Desertification

proteins - How to bind antibodies to study their properties?

Like any other protein, antibodies will aspecifically bind nitrocellulose or PVDF membranes, but any other protein present in your antibody preparation will also do.



Depending on the antibody class, more specific binding can be obtained with protein A or protein G, that recognize the Fc domain. It's usual to have protein A/G immobilized on a stationary phase like agarose.



If you know the antigen used to develop the antibody, you can also use the immunizing peptide crosslinked to CnBr activated sepharose as a probe to bind your antibodies.



Knowing something more about your antibody preparation and what exactly is the 'behavior' your want to study could help obtain better answers.

vision - Why do we squint?

Recently, I was having an eye exam and admitted to squinting my eyes to sharpen blurred edges. Later, while waiting for the dilation to set in, my brother (a would-be pharmacist fresh off an anatomy course) was telling me about how vision works.



As a non-scientist, here's as much as I gathered:



  • The pupil allows light into our eyes.

  • The lens bends and shifts to focus that light against our retina.

  • The retina translates this light-information into signals via the optic nerve.

  • Something about brains, and then sight!

So, my question is, if the lens being bent and shifted inside of our eye by muscles is how our eyes focus, why do those of us with poor vision squint? Surely it can't be that by narrowing my field of vision I'm consciously bending my lens.

Friday, 11 May 2007

microbiology - How to learn biomathematics?

MathsBio is quite a large field. It is an interdisciplinary branch having utility in a lot of branches in biology like biophysics, biomedical, genetics and molecular biology. Applied Mathematics is generally used in modelling and understanding biological phenomena where we have to deal with large amount of data, for example the use of graph theory for analysing biochemical networks. Systems biology is an emerging field which uses a lot of mathematics.



You should pick a book depending on the field in which you want to use mathematics, though having knowledge of elementary biology is necessary. I am suggesting some books which cover wide application of mathematics in biology.



Mathematical Biology: I. An Introduction by JD Murray



For systems biology:



Mathematical Modelling in Systems Biology: An Introduction by Brian Ingalls

Wednesday, 9 May 2007

neuroscience - If people with colorblindness lack one type of cone cells, shouldn't they be unable to recognize one particular color?

The 3 types of cone cells in normal humans allow them to view 3 types of colors and any color made from mixing and matching those 3.



So, 2 types of cone cells should only allow to view just 2 types of colors and any colors made from those two.



But that is clearly not the case.



https://en.wikipedia.org/wiki/Color_blindness#Red.E2.80.93green_color_blindness




Protanopes, deuteranopes, and tritanopes are dichromats; that is, they can match any color they see with some mixture of just two primary colors (whereas normally humans are trichromats and require three primary colors).




Also, from personal experience, I'm colorblind and can see and differentiate all 3 red, green, and blue. It's just the hues between red-green and green-blue I can't distinguish much...



How exactly do dichromats see all three colors when they lack one type of cone cell?

neuroscience - Do brain cells shrink during REM sleep or a lucid dream?

For those who have access, here's the full text.



Having read the paper, I can't give you a good answer. This study was performed in mice, not humans, and "sleep" was achieved in a few ways. Mice normally sleep most of the day, so it was easy to get mice sleeping normally. They also induced "sleep" through anesthesia (incidentally, they saw these same results in anesthetized mice, which I think is quite interesting). The state of "sleep" was confirmed mainly through the measurement of brain waves, in particular the delta wave. Delta waves correlate to deep sleep, and that's what they measured. Panels D and G from figure 1 (below) basically confirm just that - the mice were asleep - and that's all we know so far. More exciting research to be done!



Figure 1

Tuesday, 8 May 2007

human biology - Are (baseline) high blood levels of melatonin associated with either circadian rhythm or mood disorders?

(Exogenous) melatonin is administered at night for treatment of circadian rhythm disorders, but melatonin taken during the day is linked with depression.



I would like to know if high blood levels of (endogenous) melatonin (at a steady state, throughout the day) might be linked with mood or sleep disorders (or have any effect at all), or if the body's response to melatonin adjusts accordingly.



I think the answer to this SE question is related, but I can't find the source using a reverse image search.

Monday, 7 May 2007

evolution - How does natural selection favour large body mass and size (or so it seems)

I was walking through a park this afternoon and observed a few birds having fun flying around and it got me thinking why would natural selection favour birds with flesh at all if it hinders their flight.



We started first with single-cell and micro-organisms flourishing the ponds and then they evolved into massive dinosaurs. It therefore seems, there are some unique reasons for growing to such a large size.



However, I thought it's counter intuitive because the large body slows down locomotion, requires lots of food and energy upkeep, is a big flesh target for predators, makes hiding ineffective.



Although it is obvious that the flesh protects the internal organs, but it seems like a chicken and egg problem because without a massive body, perhaps then there is no need for the internal organs.



On a different perspective, perhaps those animals that evolved without flesh are called plants.



That sums up my naive train of thoughts.



So, any expert can shed some light?

Friday, 4 May 2007

human biology - What could account for an apparent loss of mass at death?

Snopes.com gives a discussion of possible issues with the original experiment. Evaporation or bowel or body movements for instance. I think the biggest complaint about the experiment is that it has not been reproducible and that the original experiment was flawed. MacDougall only took six measurements and he threw two of them out in his original work. The Wikipedia link you give cites a paper where sheep were found to gain weight at least for a time after death. Dogs are found to have no weight change.



MacDougall and his contemporaries were inclined to interpret their results such that animals simply do not have souls, or have different sorts of souls. But if you look at an average of all experiments cited, it could also be said that the average weight loss up on death averages to zero. 3/4 of an ounce of a human being (or a sheep) over the course of something like a death is not an easy measurement. You can't give them a drink of water, you worry that they are breathing too much and losing water. Its not an easy experiment, at least for human beings where you can't control the circumstances of death so well.



In any case this really needs to be measured better. In 90 years it doesn't seem that there's been a real rush to do it.



I just stumbled across this blog post that talks about an effort to measure a change in blood flow to the brain when in intense mental activity popularized in the late 19th century. The investigator Mosso claimed he measured a difference, but the result is disputed today. It could not have been more than a few grams. In any case a description of how difficult this measurement can be.

Tuesday, 1 May 2007

genetics - Does a large effective population size result in faster decay of linkage disequilibrium (LD)?

It is certainly possible as yes, rapid population growth will reduce LD. From Slatkin, 1994:




In a rapidly growing population, however, there will be little chance of finding significant nonrandom associations even between completely linked loci if the growth has been sufficiently rapid.




Or Nature Reviews, 2002




Przeworski... showed that population growth tends to decrease the extent of LD, especially for longer periods of growth. By contrast, population subdivision tends to increase the extent of LD, especially when a sample contains individuals from several strongly differentiated subpopulations.




See also box 1:




Rapid population growth decreases LD by reducing genetic drift.


bacteriology - Do sulfate reducing bacteria help during the formation of the mineral dolomite in low temperature environments?

Do sulfate reducing bacteria help during the formation of the mineral dolomite in low temperature environments?



Wikipedia says




The actual role of bacteria in the low-temperature formation of
dolomite remains to be demonstrated. The specific mechanism of
dolomitization, involving sulfate-reducing bacteria, has not yet been
demonstrated.




I wonder if someone has any updates on this. The reference given in the Wikipedia article is from 2000, from a source titled suspiciously "Journal of Conference Abstracts". Now it's 2013 and maybe someone else has found out something new.