Is Cas9 unique in it's ability to act in response to a specific DNA sequence? As a computer scientist, I'm interested in the ability of the Cas9 protein to function as an if-gate for DNA. It opens up so many questions for me. Right now the protein works as "if the sequence matches, cleave", but perhaps you could customize it to do "if the sequence matches, [do arbitrary action]". However, I'd feel very dumb if I got all excited about this and it tuned out "no... there are plenty of things that function as [if sequence matches], the real revolution of CRISPR/Cas9 is... [something else]". Is my fear qualified?

There are two classes of proteins that I can think of off the bat that are DNA sequence-specific. First are restriction enzymes, which recognize a specific (usually short) sequence of DNA and cleave it, sometimes through both strands at the same spot (blunt ends) and sometimes leaving an overhang or "sticky end".

The other class is transcription factors. Instead of altering the DNA, these proteins bind to a consensus sequence and act as a gathering point for the transcription machinery to bind and begin transcribing the following gene into RNA.

What makes the CRISPR/Cas discovery unique is that the binding sequence can essentially be an arbitrary sequence, defined by the scientist, allowing for cuts just about anywhere. Transcription factors and restriction enzymes depend on the local sequence of the DNA itself, so they only bind in certain spots.

There are other sequence-specific technologies available, such as TALEN, but they are basically a combination of a site-specific transcription factor and a fairly non-specific restriction enzyme or nuclease fragment engineered into it that cuts at a specific, user-defined site, depending on which subunits are used. CRISPR is a much more powerful (and easier to implement in vivo) technology, though, so while TALEN still has a place in the molecular biology toolbox, CRISPR is rapidly eclipsing it.


What is the intracellular chloride concentration in rat T-cells or thymocytes I'm modeling acid-base in T-cells as based on Grinstein J Gen Physiol 1984; 83: 341-369. I have an estimate of strong ion difference (SID), and Grinstein gives Na and K, but for SID to be true at 33 mM with K 147 mM and Na perhaps 20 mM Cl should be  (K + Na) - SID = 134 mM which is hard to believe but I could find no data on the subject.

Felber and Brand 1982 estimate the intracellular T-cell chloride concentration to be about 30 mmol, which seems to me to be on the high end for intracellular chloride in mammalian cells (though my experience is mostly with neurons, I'm not as confident of intracellular chloride concentrations in other cell types; for a neuron I'd expect <10mmol). Still, that leaves a big anion gap for your SID estimate.
I think it is more likely that your SID estimate is simply wrong. The number you report sounds like an extracellular SID; Kowalchuk et al 1988 suggest intracellular SID is about 4X extracellular for muscle, which sounds about right for your situation as well.
Most of the intracellular anion contribution is provided by negatively charged proteins, amino acids, lactate, etc, rather than strong ions like chloride. Many of these are nearly completely deprotonated at physiological pH, though (for a typical amino acid the first pKa is ~2).

Felber, S. M., & Brand, M. D. (1982). Factors determining the plasma-membrane potential of lymphocytes. Biochemical Journal, 204(2), 577-585.
Kowalchuk, J. M., Heigenhauser, G. J., Lindinger, M. I., Sutton, J. R., & Jones, N. L. (1988). Factors influencing hydrogen ion concentration in muscle after intense exercise. Journal of Applied Physiology, 65(5), 2080-2089.


Health effect of electromagnetic and acoustic waves on brain function What if any effects are there on brain function from prolonged exposure to electromagnetic or acoustic stimulation?

The question is extremely broad.
Electro Magnetic signals
Even this subquestion is very broad. Electro magnetic signals encompass a lot of phenomenon, some of them represent health risks, some of them don't. It is funny to wish to limit the health effect to brain in your question as to reduce the scope of the question given how variable are difference electro magnetic waves can have on matter overall.
Ionizing radiations
Ionizing radiations will obviously represent health risks. But even non-ionizing radiation can pose health risk.
Non Ionizing radiations
Microwave
You are probably aware that you should not put your cat in a microwave!
Retina damage
Intense light can cause photochemical damage to the retina. See here.
Intense infra-red
High intensity infra-red affect cells (see König et al. 1997)
Cell Phone
Overall, there is likely no impact of cell phone radiation on our health. If there were any, it would be minimal.
See this Veritasium video: Do Cell Phones Cause Brain Tumors?. You should also have a look at the skeptics.SE post Do mobile phones have anything to do with brain cancer?.
Cell phone towers
Likely has no health effect. See Do cellphone towers cause health issues?
Other electro magnetic signals
For more information, you should have a look at WHO > Electromagnetic fields and public health: radars and human health
Sound wave
Some sound can cause hearing loss. The frequency of this sound, the intensity and duration of exposure to the sound are all important in determining the degree of the hearing loss. Have a look at this article from the American Hearing Society for more information.


what is the principle behind Allele Frequency Net Database I just wanted to know what is the basic principle of Allele*Frequency Net Database. How are the frequencies present in them calculated??

Allele frequency is simply the frequency at which a specific allele is found in members of a population. Let's take the following example from the site you referenced:

The first column merely has the name of the allele, A*01. The second column is the population from which individuals were genotyped. Skipping ahead, the fifth column is the number of people genotyped from the population, 187 in this instance. Of those 187 people, 14.8% of them have at least one copy of the allele as stated in the third column. It's important to remember that each individual could potentially have two copies of the allele.

The fourth column gives the actual allele frequency, calculated by the number of A*01 alleles/number of total alleles (374, assuming no serious mutations). Of those 374 total alleles, 7.4% (0.074) of them are the A*01 allele, meaning 27-28 of the 187 total people had the allele. Since 14.8% of people had the allele, but the frequency of the allele was only 7.4%, we know that each person who has the allele only has one copy of it.


Is it possible to trace of the ancestry of a person by only using his/her genetic information? Is it possible to trace the descent of a person only using his/her genome sequence?

In short, yes, it is possible. There are companies that sequence part of your genome and then can trace it back to your ancestors. All human family trees can be traced back to their African origin 200 000 years ago, but the companies that sequence your genes do not do that. For example, 23andMe sequences only 1 million of your base pairs (single nucleotide polymorphisms (SNPs)). They trace your most recent heritage, which could lead to Europe, Africa, or Asia. They can basically trace which part of your chromosomes (and thus your ancestry) came from your mom or your dad:

  Unlike the sex chromosomes and the mitochondrial DNA, which are inherited as blocks, the 22 biparental chromosomes, known as autosomes, are scrambled during reproduction. Through a process known as recombination, each parent pulls his or her paired set of 22 autosomes into chunks, then reassembles a new single set using half the material from each pair. The two single sets of chromomes from each parent are combined into a new paired set when a sperm fertilizes an egg.

You can read more about 23andMe here. There are other companies that are specialized in tracing your ancestry: Genetic Genealogy, DNA Tribes, and Heirlines.


Feeling warm and cool breezes - how does it work? As you travel with your hand sticking out of a car the sensation you have is one of cooling: even though molecules are transferring energy to your hand, you interpret it as being colder. Now, at a certain speed your hand would actually melt down, and I'm assuming you'd be feeling warmth by the time that happened.

I'm wondering how this works: how can your body sense warmth and cold from a phenomenon that, physically speaking, is just about molecular collisions?

You have many different types of sensors in your skin; you probably feel the pressure of the air moving past your hand in addition to the temperature.

The temperature increase in your hand due to collisions isn't very significant, you have to be going at really high speeds to encounter that phenomenon (spacecraft reentry would be an extreme example, for example see this wikipedia page).

Temperature changes due to evaporation are probably most significant (this is why even warm air blown from a fan can feel cool, especially if you are perspirating), as well as the temperature of the outside air around your hand compared to the air inside the car.


Does difference in expected life duration between men and women have biological nature? It is known that men in most countries live less than women. I wonder whether it is due to different life conditions or because male and female organisms differ?

For example, I heard that testosterone may cause cardiovascular deceases. Is it true? Are there other biological mechanisms that can shorten men's lifespan?

There are several explanations. Probably these are all true to some degree and thus combine to give the general longer life expectancy of females.

Most of these statistics are from Annex 2 of the WHO Health Report 2004 (found through Wikipedia)

Males are more likely to get lung cancer, liver damage and other drug-related illnesses (implied would be that males are more often alcohol/tobacco/drug users).
Males also die more often as a result of work-related injury, especially as soldiers
Males are usually larger. There seems to be a small inverse correlation between size and life expectancy
Mitochondrial DNA is passes from mother to child. As such, mutations harmful for men are less effected by natural selection.
Men have one X chromosome, while women have 2. The y chromosome is very small and contains almost no genes. Thus if there is a genetic defect on the X chromosome the female might have a healthy X chromosome to compensate while the male does not have one. Among others this makes males more likely to have hemophilia or color blindness.


Are cortical columns restricted to somatosensory cortical sections? From this previous question, it seems like evidence for the minicolumn organisation of the neocortex seems to be primarily based off observations around the sensory parts of the cortex, such as the primary visual cortex and the barrel cortex. Have column-like organisation been observed in non-sensory regions of the neocortex?

Cortical columns (also called minicolumns) are not limited to the somatosensory cortex. As shown in this paper (which discusses how the miniucolumns change in response to aging), it is also present in the associative cortex.

However, it should be noted that "minicolumn" in this paper is defined as neurons that are close together and form a minimum spanning tree, as shown below.

Connectivity doesn't seem to be analysed, probably because connectivity information is really painful to collect, but I'm not sure given I'm an amateur when it comes to neuroscience.


Why isn't the phosphoglycerate kinase reaction of the glycolysis pathway irreversible? Step 7 of the glycolysis pathway is the conversion of 1,3-bisphosphoglycerate into 3-phosphoglycerate by the action of the enzyme phosphoglycerate kinase, resulting in the production of 2 ATP molecules (per glucose).

This reaction has a large negative value of ΔG (-18.5 kJ/mol). If reactions having large negative value of ΔG are classed as being irreversible, then why is Step 7 of Glycolysis reversible?

The free energy change that you quote for the phosphoglycerate kinase (PGK) forward reaction is, of course, the standard free energy change (ΔG0') for the overall reaction. The standard free energy change is defined for all reactants at a concentration of 1M. Note that this value includes the formation of ATP -  the free energy of hydrolysis of 1,3-BPG would be much larger, and some of that energy is 'captured' in the ATP product.

The actual free energy change for the PGK reaction, ΔG,  will differ from this value because of the fact that the actual reactant concentrations are very far from the idealised 1M. You can find a Table here which compares, for each step in glycolysis, the standard free energy change with a true free energy change, calculated on the basis of cellular conditions in erythrocytes (also shown). You will see that for the PGK step the actual free energy change is 0.09 kJ mol-1 rather than the -18.9 kJ mol-1 that you quote in your question.

You can also see from the Table that there are only two reactions in the glycolytic pathway with large negative values for ΔG: those catalysed by phosphofructokinase and by pyruvate kinase. These are of course the two steps that are bypassed in gluconeogenesis because they are essentially irreversible.

So - your reasoning was correct, but it was based on the wrong ΔG values.

added much later

As pointed out in the comments, the 1st step in glycolysis also has a large negative value for ΔG and is also bypassed. Not sure how I forgot to include that!


How does the structure of the pancreatic acinar cell relates to its function? So the pancreatic acinar cell synthesizes, stores and secretes digestive enzyme precursors called zymogens e.g. pepsinogen.

The structure of the acinar cell shows that there is an apical and basal side. The basal half of the cell is almost entirely filled with rough endoplasmic reticulum which can be shown with pyronin stain showing up pink due to the rRNA of ribosomes. The nucleus is also on the basal side which explains why rER is there too, since the nuclear envelop is connected with the ER membrane. Zymogen granules are on the apical region. Any thoughts as to why there is this polarity in cell?

The secretion pushes the cell organelles to the basal part.

(although the fat cells have no polarity, their organelles have been pushed to one side of the cell:

Comparing to adipose cells, the acinar cells secrete their specific proteins on one specific end of the cell, this is why in contrast with fat cells they have well defined polarity.


Cortical projections from layers 2/3 back to 4? As all excititory neurons in layer 4 are stellate - they have no apical dendrites that could project to layers 2/3. However, I have seen some diagrams showing axonal projections from layers 2/3 back to 4, but then I see other diagrams that don't show it.

Is there enough evidence to show axon projections from 2/3 to 4? If so why do so many diagrams leave them out?

Excitatory neurons in layer 4 are not all stellate in all cortical areas, for example see Smith and Populin, 2001 who show clearly that in auditory cortex most excitatory cells in layer 4 are pyramidal. There are also many cortical areas that have no clear "layer 4" and also do not contain spiny stellate cells.

In general, intracortical circuitry is not fully understood. Although your question shows understanding of this next point, let me highlight it anyways because it is a point that is often forgotten: neither axons nor dendrites are constrained to the layers containing soma. Therefore, it is possible for a cell of "layer A" to contact a cell of "layer B" even if the "layer A" cell has no axons in "layer B" and the cell of "layer B" has no dendrites in "layer A": they could have axons and dendrites in "layer C", for example.

One approach has been taken by some such as Binzegger et al., 2004 is to estimate intralaminar cortical connectivity based on co-occurrence within a given layer of axons and dendrites. This approach is an approximation, of course, because there is no guarantee that axons contact dendrites randomly within a given layer. For example, axons could preferentially contact the dendrites of inhibitory rather than excitatory cells, and this would fundamentally influence the circuit dynamics.

The result from Binzegger et al (their Figure 1 is a fairly clear summary figure, if you want to start there) is that, although there are some predominant patterns of connectivity, there is no pure feed-forward circuit: all of the connections are at least partially reciprocal. For the example you gave, layer 2/3 to layer 4, the number of connections from layer 2/3 to layer 4 is estimated to be about half as many as the number of connections from layer 4 to layer 2/3.

Figure from Binzegger et al, 2004; Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License

However, it is also possible that these connections preferentially target inhibitory cells rather than excitatory cells in layer 4: see Thomson et al., 2002.

It is likely that the variety in sources/diagrams you are familiar with is simply because people take different approaches to complex systems (and different approaches may be warranted in different situations). Some people choose to highlight the most salient features, perhaps the strongest layer-to-layer connections, in the hope that this produces an understandable, though simplified, model. Other people choose to highlight the vast complexity, emphasizing all of the smaller details that may actually be important.

For an analogy, a chef is likely to just deal with olive oil. They don't care that olive oil is actually a collection of several fatty acids: it's just olive oil to them, and the importance to them is that olive oil is distinct from another vegetable oil. A biochemist, however, might be interested in the specific fatty acids and might point out that those specific fatty acids are found in all sorts of other oils. Neither one is likely to convince the other that they have the better answer for all purposes.

Neither approach is strictly incorrect or better than the other, until better understanding makes one of the approaches obsolete.

References:

Binzegger, T., Douglas, R. J., & Martin, K. A. (2004). A quantitative map of the circuit of cat primary visual cortex. Journal of Neuroscience, 24(39), 8441-8453.

Smith, P. H., & Populin, L. C. (2001). Fundamental differences between the thalamocortical recipient layers of the cat auditory and visual cortices. Journal of Comparative Neurology, 436(4), 508-519.

Thomson, A. M., West, D. C., Wang, Y., & Bannister, A. P. (2002). Synaptic connections and small circuits involving excitatory and inhibitory neurons in layers 2–5 of adult rat and cat neocortex: triple intracellular recordings and biocytin labelling in vitro. Cerebral cortex, 12(9), 936-953.


Ancestral Allele and Hapmap I notice on dbSNP rs6352 has an ancestral allele of G - http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs6352

The hapmap in humans for this allele is very rare, the homozygous version practically not existing at all http://hapmap.ncbi.nlm.nih.gov/cgi-perl/snp_details_phase3?name=rs6352&source=hapmap3r3_B36&tmpl=snp_details_phase3

My understanding has been that the ancestral allele refers to the common gene that an ancestor in all humans once shared. Now, I thought the ancestral allele was usually the most frequent in a population, but I can see this was most likely a wrong assumption.

Was it a wrong assumption, or was this example above just a rare exception? Is deviation from ancestral alleles nearly worthless as a metric to investigate possible mutated alleles that may be leading to disease? I realize the proper answer may be too long, but just a brief summary would be appreciated.

Many thanks.

It is kind of confusing.  Here's the sequence, from the ncbi link

GGACATTTAAMGAGGTACGTG

So M is "A or C"

Its a missense mutation, the amino acid called for is either an N or a K.

GGACATTTAAAGAGGTACGTG = K amino acid

GGACATTTAACGAGGTACGTG = N amino acid

GGACATTTAAGGAGGTACGTG = K amino acid

GGACATTTAATGAGGTACGTG = N amino acid

When you blastx it, the top hits are all the K allele, across a few species.

When you blast the DNA, the non-human hits in nr all have a G, not an A or C.  So I guess that's why they are calling that the ancestral allele.  The human hits to nr all have A, so the K amino acid is conserved.


DNA extraction kit for microbial mats, rocks, and soil in a remote area I am hoping to perform a metagenomics study of samples from a lava tube. It will be in a remote area (with no large scientific equipment) and I would need to bring all scientific equipment myself. For the sequencing, I plan to use either the Field Sequencing Kit or the Rapid PCR Barcoding Kit from Oxford MinION. However, I am unsure how to extract DNA before using the Oxford Minion kits (and in a manner, of course, that complements it).
Are there DNA extraction kits that can followed up Oxford MinION kits and can be performed without heavy equipment for the following sample types?
a) microbial mat
b) soil
c) lava rock
Thank you for sharing your advice!

Those are some pretty tough samples to get high-quality DNA from, even in a lab. Your best option is probably to place samples in a nucleic acid preservation buffer and carry them out for extraction later.
That said, there are some potential solutions. Akonni has some kits that don't use any centrifugation and they claim they'll work on soil and stool, so they might be good enough for your applications. They kind of seem like they're based on the same principle as this kit-free protocol (this protocol is for Plasmid DNA, but I'm sure it could be adapted for Genomic DNA with a little R&D on your part). In either case you'd probably want to look into a portable bead-beater to disrupt/lyse your samples. This will shorten your DNA fragments through shearing, but it's probably necessary to get good extractions from any of these materials.
A few companies also make portable centrifuges that run on 12V car plug adapters, assuming you'll have a vehicle somewhere within walking distance. That could open your options up to using a Powersoil kit or even something like a phenol-chloroform extraction, which you might not need a bead-beater for. (Note: you absolutely would need a properly fit-tested, full-face respirator with the appropriate chemical filters to do phenol-chloroform work without a proper fume hood, plus a way to haul out your waste).
If it were me, I'd still probably use a preservation buffer and do the extractions and analysis back at the lab.


Island model vs. stepping stone model Wright's Island model and Kimura's stepping stone model are classic explanations for migration/gene flow o individuals between subpopulations within the field of population genetics.

My question concerns the quantity Nm, the (effective) number of migrants per generation.

In the Island model, where all demes are exchanging migrants at a given time, individuals migrate with a frequency of m, as seen in Wright's approximation for $F_{ST}$

$F_{ST} = \frac{1}{4Nm + 1}$

In Kimura's stepping stone model, individuals can only migrate to an immediately neighbouring subpopulation with a frequency of $\frac{m}{2}$.

My question is:

In the stepping stone model, are there still only $Nm$ individuals migrating, or is it now $\frac{Nm}{2}$?

My thinking is that an individual can either move left or right, each with a frequency of $\frac{m}{2}$, for a total of $\frac{m}{2}$ + $\frac{m}{2}$ = $m$, so that there are still $Nm$ total migrants. Am I correct in my thinking or should it really be  $\frac{Nm}{2}$?

It all depends upon how $m$ is defined and that might vary from a paper to another. The rest, I find, is very much just a question of logic.

In the infinite island model (the model from which Wright's approximation was computed), the total number of migrants is of course, infinite (if $m≠0$). With $d$ demes (or islands), the total number of migrants is $dNm$ if $m$ is defined as the migration rate between any two patches.

Under a linear stepping stone model with only 1 step (because there exist more complex stepping stones models), with $d$ demes (or stones), the total number of migrants is $dNm$ (minus small approximation for the extremities of the world) if $m$ is defined as the migration rate from one deme to an adjacent deme. Half of $dNm$ are migrating toward the left and half of them are migrating toward the right.

  I thought that may be the case. Was SimBit designed assuming NmNm or Nm2Nm2?

In SimBit, you can use multiple modes to enter migration information. You can specify the migration rate from any patch to any other patch (mode A).

You can use island where you specify the probability of not migrating (which might arguably be a little unintuitive). If the probability of not migrating is $x$, and there are $d$ demes, then the number of migrants from one deme which patch size is $N$ to a single other deme of interest is $\frac{N(1-x)}{d}$. The number of migrants from this deme to any other deme is $N(1-x)$ and the total number of migrants in the whole (meta)population is $dN(1-x)$.

The mode LSS (Linear Stepping Stone), is a little complex as it is very flexible. You can specify the migration rate from a focal patch to any other patch considering they are place in a linear order. SimBit LSS indeed allows for stepping several stones apart if you want. If for example you input LSS 3 0.1 0.8 0.1 2 it means that the probably to migrate from any patch to a given adjacent patch is 0.1. The probability of migrating is 0.2 and the probability of not migrating is 0.8. With such model, the number of individuals exiting a given patch is $0.2N$ ($0.1N$ on each side) for a patch of size $N$. Assuming all patches have the same size, the total number of migrants for a (meta)population of $d$ patches is $0.2dN$.

Of course, if you allow for patch size to vary with carrying capacity or for migration rate to be affected by population mean fitness, then this expected number of migrants will vary among generations.


Can anyone help me identify this insect? I'm trying to identify the insect below that I found in Edmonton, Alberta, Canada. Any help would be appreciated.

This a long-horned caddisfly (gallery), which belongs to the superfamily Leptoceridae, though, due to a combination of the quality of your image, as well as limited available resources online, I'm currently not able to confidently suggest a genus or species. At any rate, here are a few pictures of various caddisfly that resemble the characteristics of your posted insect.

Unkown genus & species

Ceraclea dissimilis

Ceraclea sp.

Ceraclea slossonae

From where the majority of what I believe to be the closest matches mostly all belong to the genus Ceraclea, I am currently leaning towards that, however, I will continue to search for further validation.


What are reasons we know insects evolved on land rather than water I am reading up on the evolution of insects, and insects supposedly evolved on land rather than water. How do people know?What evidence is there that insects evolved on land and not water?

The sister group of hexapods (Insects plus Collembola, Protura, and Diplura) are thought to be Remipedes. Remipedes are cave-dwelling aquatic pancrustaceans. The most recent common ancestor of Hexapoda and Remipedia was likely aquatic. But somewhere along the pathway to becoming modern hexapods, after they split from the lineage leading to modern remipedes, the ancestors of modern hexapods developed tracheal respiratory systems that function on land. So the evidence comes from the fact that the extant lineages of insects, close to their most recent common ancestor, including Collembola, Protura, Diplura, Archeaognatha, and Zygentoma are all terrestrial.


Query regarding calculation of survival analysis According to this tutorial, for table to find the survival estimates, the square root of the 6th column is multiplied with the 4th column, which is Survival probability. The value that should come for the 7th column for the 2nd row is 0.052((square root of 0.003)*0.950=0.052) but in the tutorial it is given 0.049. Am I making any mistake with the calculation?
Many of the values in the table does not match with the calculations given.

"0.003" is rounded up; the exact value is 1/380, which is 0.00263157894... (and some more decimal places).

If you calculate the table entries to a few more decimal places, you get 0.04873397172 (and so on), which rounds up to 0.049.


Does the hepatic portal system form capillary beds? Does the hepatic portal system form capillary beds?  If so, is the capillary bed coordinated with that of arterial capillaries?

What review paper might I look in?

In anatomy, a "portal circulation" is simply when you have a capillary bed that is interposed between two venous circulations BEFORE blood flows back to the heart. There are a couple of places in the body where this occurs, including the liver (hepatic portal system) and the pituitary (hypophyseal portal system).

To answer your question... yes, the hepatic portal circulation drains into the liver sinusoids, which is one large capillary circulation.

The hepatic arteries and portal vein give off branches that make up the portal triad which delivers blood (both arterial and venous blood) to the functional units of the liver which are the hepatic lobules.

The hepatic portal system drains into the liver and forms a highly fenestrated network of capillary beds within the liver parenchyma. In the case of the hepatic portal circulation, the flow through the liver sinusoids is considered this capillary bed. In humans, the flow of blood that makes up the hepatic portal circulation is mostly venous blood from the gastrointestinal tract.  This allows blood to flow through the liver for clearance of substances like drugs and hormones before those substances reach the peripheral circulation. Specifically, arterial blood flows to the majority of the stomach, small intestine and colon from the celiac, superior and inferior mesenteric arteries. This arterial blood flows through the capillary beds in the mesenteric circulation (i.e. the capillary beds around the intestinal enterocytes) and then into the major veins that drain the intestinal tract. There are two major veins that drain the intestinal tract, the superior and inferior mesenteric veins. The inferior mesenteric vein drains into the splenic vein and then the splenic vein and superior mesenteric veins merge to form the portal vein of the liver. Once blood flows into the portal vein it flows through the hepatic sinusoids (another capillary bed) before flowing out of the hepatic veins into the inferior vena cava, and then back into the heart.

The figure below is a picture of the intestinal veins from Gray's Anatomy  (wikipedia) that form the hepatic portal vein, the superior and inferior mesenteric as well as the splenic vein. In the figure the older term lienal vein is used instead of splenic vein. The latin word for spleen is lineal.

The picture below is a schematic of the hepatic lobule that receives its blood from a portal triad. In the center of the lobule is the "central vein". The blood flows from the portal triad to the central vein, and then the central veins coalesce to form the hepatic veins (which then drain into the inferior vena cava). The picture below is available from this website, along with some other text and picture for more information.

And another nice picture from wikipedia on "hepatic lobules".
.

As for a "freely available review" that you asked for, I can't find any with better pictures from PubMed that what is already in this answer.


What is the evolutionary advantage of having pubic hair? Only humans have pubic hair. What is the evolutionary advantage in having it?

Many consider pubic hair to be a sort of protection or warmth, however this can only hold true for the vagina, since pubic hair doesn't offer any additional protective advantages to the male urethra. The most prevailing theory is that simply it is one of the odor producing parts of the body and humans (like most life forms in general) are simply aroused by strong smells. Also most odour producing parts are usually accompanied by hair in order to "catch" pheromones. It is notable that those odours are not the direct product of glandular secretions, as those secrations are in fact odorless. It is their combination with bacteria that gives every person a unique smell. This unique smell gives a lot of important information to the canditate sexual partner. Here is an interesting study about odour importance in sexual reproduction as well as the role of MHC(Major Histocompatibility Complex)

If you are interested you can read further for for the Importance of smell in sexual production


Reasoning behind CO2 mouse euthanasia precharge prohibition I have been at two universities now and the first permitted the precharging of a cage with co2 before a mouse is put in, but the second does not. I was wondering what the reasoning is behind the ban on precharging a cage with Co2.

When I think about this, it seems that it would be less stressful for the mice to fall unconscious very quickly rather than a slow and gradual suffocation. Is there some shock associated with the precharged cage that makes this more stressful in some way?

Quoting from guidelines to CARBON DIOXIDE EUTHANASIA OF RODENTS from University of Pennsylvania >>

  Do not “pre‐fill” the euthanasia chamber with CO2.  Start with room air then slowly fill the chamber with CO2 over several minutes
  (OLAW).  CO2 is heavier than room air, thus the chamber may need to be
  “purged” between groups of cages.

  “Because inspiration of high
  concentrations of CO2 is both aversive and painful, a recommended
  procedure is to place animals into a chamber that contains room air
  and then to gradually introduce CO2.” (ACLAM)
  CO2 first renders the animal anesthetized and then, with adequate exposure time, will result in death by CO2 narcosis.  Animals should
  be left for additional time within the euthanasia chamber, after
  spontaneous movements have ceased, with CO2 continuing to flow.

  “Animals should be left in the container until clinical death has been
  ensured.” (NIH)

Also, according to an article in The Scientist by Kerry Grens >>

It's been realized that at high concentrations, CO2 causes creatures torment. After reaching mucosal surfaces, it transforms into carbonic acid, which stings. Also, in people, even low fixations can be upsetting, bringing about shortness of breath.Therefore, explaining why high levels of CO2 is actually more painful for the rodents.


I really need some help with a plant identification I am trying to identify this flower. It was spotted in an Australian Botanic Gardens. I have been advised that the plant was approx 1.8m high and the flowers approx 2cm wide. Any help greatly appreciated.

That's an Apocynaceae, from the species Strophanthus speciosus. Its common name here in Australia is corkscrew flower or poison rope.

It's not native to Australia, though: it's native to Africa.

You can easily identify it by the flower:

Flowers of Strophanthus speciosus in the Royal Botanic Gardens Victoria, Melbourne (source of the image)


What class of histone deacetylase (HDAC) inhibitor is sodium valproate (VPA)? VPA is a known HDAC inhibitor. But I cannot find what class it is.

What class is it?

And is there any method of finding an answer better than floundering with Google?

This is explained at the WP page for HDAC. There are five classes:

hydroxamic acids (or hydroxamates), such as trichostatin A
cyclic tetrapeptides (such as trapoxin B), and the depsipeptides
benzamides
electrophilic ketones
the aliphatic acid compounds such as phenylbutyrate and valproic acid

and valproate is in the final class, aliphatic acids.


What is the use of male plants in nature? If pollination is done by insects like bees and through the air, then what is the use of male plants in nature?

Pollen, spermatozoid, ovules and bees

The pollen is a coarse substance containing the spermatozoids. Males plant creates these pollens. As bees visit the flowers, the pollen get stuck on their body. When the bee covered with pollen visits female plant, then the pollen may randomly stick onto the female organ. The spermatozoid grow into a tube within this organ and goes to fertilize the ovule.

In short, bees are ...

In other words, you need females for the ovaries, males for the spermatozoids and bees for the delivery services.

Note that bees don't do this delivery services just to be nice with plants. They do so because they get nectar (substance full of sugar) in the flowers.

Reality is more complex and more diverse

Note also, that reality is more complex and more diverse than what I explained. Not all plant species are pollinated by bees. Not all plant species have flowers. Most plant species are hermaphrodite (have male and female flowers or even have male and female organ within the same flower).


What does 'virus prototype strain' mean? Does the term 'prototype virus strain' mean the first virus isolated and without mutations?

A prototype virus may or may not be the first isolated virus of a group. It's essentially the same as a "reference" virus -- in fact, the International Committee on Taxonomy of Viruses
(ICTV) uses the terms interchangeably, as in the  Hepeviridae Study Group which has a column entitled "Prototype/Reference Strain".

In many cases the reference virus is the first isolate, but it isn't necessarily the case. The ICTV is the official body that determines reference strains, and they may choose a different virus as the reference/prototype. For example the first isolate may turn out to be unusual or an outlier in same way, so that a more typical strain may be chosen as a reference or prototype (I don't know offhand of examples of this though).

"Prototype" is often used in a broader sense as well, where a group of viruses can act as prototypes for a still broader group.  For example, "The genomic structure of Pencillium chrysogenum virus (PcV), the prototype of the genus Chrysovirus ... " (pdf link) uses "prototype" to refer to all the viruses in the Pencillium chrysogenum group, as compared to the broader genus.


Can plants directly use sulfuric acid? In the explanation of the sulfur cycle, it is often said that sulfur moves from the atmosphere to the ground by acid rain in the form of sulfuric acid. Can plants directly use sulfuric acid to assimilate sulfur?

Plants have sulfate transporters which they use to assimilate sulfur. Since sulfate is the conjugate base of sulfuric acid, this could be construed as a "yes" for your question. Sulfuric acid would be present in its conjugate base form at physiological pH values.

However, it would be unwise to water your plants with sulfuric acid, as many plants have an optimal pH range which will quickly cause death when sulfuric acid lowers the pH of the soil below that range. As a result, areas afflicted by acid rain may require treatment with alkaline limestone to resolve this issue.


which exact mechanism triggers the first cell differentiation after n divisions? I would like to understand which mechanism triggers the first cell differentiation after n divisions.

I read previous articles on SE and Wikipedia articles on cellular differentiation and embryogenesis but still fail to understand what exactly makes it so that starting from a given division cells suddenly start to be different.

Wikipedia claims that

  In the first hours after fertilization, this cell divides into
  identical cells. In humans, approximately four days after
  fertilization and after several cycles of cell division, these cells
  begin to specialize, forming a hollow sphere of cells, called a
  blastocyst

but do not explain why they begin to specialize.

I could imagine

that a cell has a "counter" on the number of divisions which triggers differentiation after a given amount of divisions
or a chemical substance (either cell-borne or external) forces a change in the division

but why some cells would become "cell A" and some others "cell B"?

I am fairly sure that the biochemical mechanisms which regulate the life of a grown up mechanism can explain cellular differentiation (through hormones for instance) -- I am however interested by this specific moment, this n-th division where identical cells become differentiated.

The first differentiation in human embryogenesis is from early blastomeres into trophoblast, which forms the outer layer of the blastocyst, and inner cell mass (ICM). It may be unsurprising then that cells on the inside of the 8-16 cell stage morula
differentiate into ICM whereas those on the outside differentiate into trophoblast. However it is currently unclear whether this is a causal relationship (the inside-outside model) or whether blastocyst patterning is set-up earlier in cleavage (such as in the apicobasal polarity model) or if it is some combination of the two.

You were correct in imagining that tissue patterning is determined by chemical substances: a very broad class called morphogens. Cells don't necessarily count how many times they have divided but cell division can certainly affect morphogen concentration and localisation. I suppose in some sense you could describe this as a clock. I wouldn't though, especially because mammalian cleavage is asynchronous.

One line of studies showed that a transcription factor called Tead4 specifies trophoblast$^{ref}$. It was then shown that Tead4 can be regulated by cell-cell contact (mediated by Hippo signalling) $^{ref}$. They hypothesised that the magnitude of cell-cell contact could provide a mechanism by which Tead4 localisation could be controlled in presumptive trophoblast and ICM. This could explain why the cells have different fates because inner cells are completely surrounded (more cell junctions) whereas outer cells are largely exposed to the medium. Note that I only provided that as an example of a possible mechanism. It is not confirmed and, as with any model, the real picture is incredibly more complex and likely involves many factors.

I'm reluctant to go into too much detail on this because you're asking about a complex process that is still under active study and I'm unclear as to how much information you actually want. A book could be written on this subject alone, and many review papers have been published. Here's a recent one:

Development: Do Mouse Embryos Play Dice?

I suggest you read that and then if you have further, more specific questions, we can try and answer them for you.


How do I view the simulated protein structure along with ligand in VMD? I did a simulation of a protein-ligand complex, and it has stabilized after 5 ns. I have got the respective pdb files for every ns, but when I try to view in VMD (Visual Molecular Dynamics), I cannot see the ligand. How do I select the heteroatom in the graphical representation window? My complex has 1129 + 50(ligand atoms) but while loading it just shows the protein molecule(1129).

After you load the molecule in VMD, from the menu bar select Graphics->Representations... In the box labeled Selected Atoms, type "hetero" and hit enter. You should now see only your ligand (and whatever other non-protein/DNA atoms that happen to be in your PDB file). Hit the Create Rep button, enter "protein" in the Selected Atoms box and hit enter (you can see a list of all the possible selection words in the Selections tab). You will now have a separate representation for your protein and your heteroatoms, and you can modify them with the other settings in the Graphical Representations dialog in order to make them visually distinct from one another.

If this doesn't fix your problem, open up your PDB file in a text editor and check to make sure that there are lines that start with ATOM or HETATM that correspond to the atoms in your ligand. If they aren't there, your problem isn't with VMD but with one of your prior manipulations.


Problems with analysis of small RNAseq data - Adapter trimming I have always faced a problem while analyzing small RNAseq data, at the step of adapter trimming.

Overview of small RNAseq (Illumina)

RNA is size fractionated using columns or PAGE
3' and 5' adapter ligation
cDNA synthesis
PCR amplification
Sequencing

The length of the reads is dependent on the machine and recent ones like HiSeq can provide ~200bp.

The problem, however, is with reads smaller than the max read length of the machine and this is common with small RNAs such as miRNAs (especially if the concatemer of smallRNA and the complete 3'adapter is bigger than the max read length).

The first step of analysis is trimming of the 3' adapter (Illumina Truseq: TCGTATGCCGTCTTCTGCTTGT).

Several algorithms are available to do this job and what they precisely do is to check for overlaps between the adapter sequence and 3'end of the reads and then clip the aligned region.

Now the problem is this

You can't be really sure of very small alignments because they may not really be originating from the adapters, which means that you should specify a lower limit of alignment for clipping. I usually set it as 5 (intuitively).

But if a small piece of sequence really came from the adapter then it will remain and there is no way to clip it without any doubt.

The real problem comes during aligning the reads to the reference sequence. Aligners like bowtie (which i prefer to use), generally have user defined argument for number of allowed mismatches. Bowtie generally doesn't perform very well if you allow a lots of mismatches.

Subsequently, you might lose a really valuable read.

Alternative

To avoid this problem I sometimes trim the reads to around 25nt (for miRNA profiling). This creates a new problem:

You can't really distinguish whether the read came from a pre-miRNA (a longer RNA) or from mature-miRNA (smaller RNA that arises by processing of pre-miRNA)

Does anyone have an experience or an idea about how to solve this problem?

I would first recommend you ask this question biostar as the subject matter you are inquiring about is much more relevant there.

That having been said, you have another option which is to use an aligner that soft clips 3' ends of reads specifically to account for adapter (or polyA, or whatever) contamination that might have flew under your radar.

STAR is such an aligner. If you search their mailing list archives for "clip", you should find several posts related to your question.


Why is it possible to make yoghourt with lactose-free milk? The function of the Lactobacillus bulgaricus and Streptococcus thermophilus  cultures is to ferment lactose to produce lactic acid. The increase in lactic acid decreases pH and causes the milk to clot, or form the soft gel that is characteristic of yogurt.

In lactose-free milk, all the lactose was transformed in glucose and galactose using lactase. Is it possible for those bacteria to ferment glucose and galactose instead of lactose? Or is this based on other biological reactions?

Conversion of lactose to galactose and glucose is a part of the bacterial metabolism of lactose. So digested lactose would work.

In fact, it should work for all kinds of 6-carbon sugars as lactic acid is produced from pyruvate (end product of glycolysis). See Wikipedia:lactic acid fermentation.


What is this plant with distinctive leaves? Location: Vienna, Austria

Leaf size: two big thumbnails

Plant height: large thumb

I assumed it might have come from the seeds of some fruit I ate.  I consulted these websites:

https://www.baumkunde.de/baumbestimmung/

http://www.blattbestimmung.de/blattform-herzfoermig

but found nothing. Perhaps it is neither shrub nor tree.

Edit:
This is how it looks now, ten days later:

Seedlings are often tricky to determine, but I think this may be the common weed Chenopodium album (from the family Amaranthaceae). This is common across Europe, and the leaf shape, growth pattern and the silverly underside seen on the top leaf in your picture fits well.

Here are pictures of a seeding and a larger plant:

(from flickr.com)

(from https://plants.ces.ncsu.edu)


Are progenies factually half-clones of the parents? Given that a "clone" (if anything, in the context of human cloning) is taken to be, as far as I have understood, a specimen possessing the same genome as his "father/mother", aren't all "non-cloned" organisms born out of inter-individual, heterosexual reproduction (i.e. "standard" sons and daughters), effectively "half-clones", under that same definition?*

Are "normal" sons and daughters "half-clones", as a matter of fact?

A progeny is not a half clone of its parents.

Each cell expresses both maternal and paternal genes. There are no parts of the body or even a cell for that matter that is identical to one of the parents.
When haploid gametes form, chromosomes are randomly segregated. So the gamete receives either paternal and maternal chromosomes (grandparents of the progeny) randomly. This technically means that the gamete is not an exact half of the parent's genome.
During gameteogenesis (production of sperm/ovum), genetic recombination happens between nonsister chromatids of homologous chromosomes (meiotic crossover). This mechanism creates a small shuffle in the haploid genome that the gamete is carrying.


Extract protein sequences from a GBK(GenBank) file without scripting How to extract protein sequences from a GBK(GenBank) file without scripting?
I know that writting a script using BioPerl or Biopython can do this, but it is not elegant and daunting to beginners and biology persons. Any thing like

$ SOME_PKG_MANAGER install PKG
$ CMD ab.1234.gbk > ab.1234.faa

My colleagues and I have recently published a toolbox of command-line utilities that are modeled after GNU Textutils (e.g. grep, cut, tr, uniq) called FAST: Fast Analysis of Sequences  (cite).

To install FAST you can use:

perl -MCPAN -e 'install FAST'

Or install the current development version from github. The FAST install comes with a cookbook, sample dataset and all utilities have man pages. The cookbook is also available on the github wiki.

To convert the features annotated in a genbank file to fastA sequences you can use gbfcut. Below are examples of using gbfcut:

To convert all annotated features of a genbank file to fastA format:

gbfcut genbank-file

Output only tRNA features:

gbfcut -k tRNA genbank-file

Output all feature sequences with a "note" qualifier containing "telomere":

gbfcut -q note=telomere genebank-file


How did the moray eel evolve a pharyngeal jaw? I am referring to the retractable second set of jaws in the moray eel.

How can one imagine such an evolutionary step to have occurred? Just by chance an eel grew a second internal jaw and it was luckily attached to some muscles which made it useful for swallowing prey?

well considering jaws originally evolved from the first set of gill arches and eels still have gill arches, so it's not that much of a stretch. Most fish gill arches already have muscle attachments that aid in swallowing and breathing. Many bony fish already have  pharyngeal teeth to aid in swallowing (they teeth prevent the prey from being pushed back out of the mouth by water pressure. Moray eels have a much more direct mechanism becasue they live in burrows and can't fold the gill arches out to generate suction and pull food down the mouth as other fish do. So instead the muscles pull the arches backwards and the shape pulls them together pulling food down the gullet.

it has actually happened independently in cichlids and something similar happened in Snakes and Mosasaurs


A question about the intersection of evolution and thermodynamics From this 2014 article in Quanta magazine by Natalie Wolchover there is a quote from a physicist with an intriguing idea about evolution:

“You start with a random clump of atoms, and if you shine light on it for long enough, it should not be so surprising that you get a plant.”

Jeremy England's idea is that the attributes associated with life have a lot to do with absorbing and dissipating energy. He insists he is not saying Darwin is wrong, and that his thermodynamics-based idea in some sense subsumes Darwinian evolution.

(The Quanta article links to a recent paper of England's which is somewhat technical, but deals with bacterial replication and thermodynamics. I include the link to give a sense of his ideas in his own words.)

My question is  whether his idea, taking it at face value, might furnish a better explanation of something already explained in Darwinian terms or fail to account for some detail of current evolutionary theory?

So if someone had a lot of examples of different aspects of evolution s/he might be able to say, "Here is a situation in which the thermodynamics do not work out as England suggests but which is explained in evolutionary terms," or conversely, "Here is something contrary to evolutionists' expectations that seems to be pretty well explained by the thermodynamics." I suspect that there are several candidates and England's paper gives a hint in one direction.

Thanks for any insights.

Some helpful reading:

Thermodynamics, Enrico Fermi (1936) [Dover reprint].
Understanding Thermodynamics, Ness (1969) [Dover reprint].
What is Life?, Schrodinger (1944).
Entropy Production..., Crooks (2008).
Schneider and Kay, Life as a manifestation of the Second Law of Thermodynamics, Math. and Computer Modeling 19 (6-8): 25-48 (1995).

The last paper is a very readable and non-technical introduction to this topic. If one works through the equations in Chapter 7 of Ness and ref. 4 the idea should be quite clear. Basically, systems (both nonliving and living) which are at some remove from equilibrium devise ways to dissipate energy that involve a decrease in entropy, increasing the entropy of the surrounding system.

Getting long for a comment

I can only comment that evolution does not proceed towards thermodynamic optimum. Adaptation is thermodynamic optimization but evolution is directionless. Otherwise the extant species would not suffer from tradeoffs (which they have even in their usual habitat). Establishment of a self replicating cell may be thermodynamically driven and given the conditions, irreversible; macroscopic evolution is like die roll where some states are randomly⁺ selected and eliminated.

⁺Not really random but a complex non-linear function which seems unpredictable

You can imagine a chamber with particles exhibiting brownian motion. Assume that particles have a random size distribution (lets say they are crystals of different topologies). Now if you keep a separator with few holes wide enough for a just one particle of a given size to pass. Then you'll end up getting only few particles of a narrower size distribution on the other side. This no way ensures that these were the most thermodynamically stable particles.


Do Alicyclobacilli produce carbon dioxide? Do Alicyclobacilli, especially guaiacol producing ones, still produce carbon dioxide? Alicyclobacillus spp. are well known spoilage organisms in the fruit juice industry. Apparently there is no "blowing up" of the packaging (often caused by carbon dioxide production) which makes it difficult to visibly detect a potential contamination. Thus the question, do Alicyclobacilli produce carbon dioxide at all?

Alicyclobacilli are strictly aerobic and thus take up oxygen and secrete carbon dioxide, as opposed to the (facultative) anaerobic yeasts and bacilli that usually cause spoilage. So yes, alicyclobacilli produce CO2. But why doesn't the packaging swell? Compare the number of gas molecules in the simplest reactions for aerobic and anaerobic metabolism:

Aerobic metabolism: $C_6H_{12}O_6 + \underline{6 O_2} \Rightarrow \underline{6 CO_2} + 6 H_2O + 38 ATP$

Anaerobic metabolism: $C_6H_{12}O_6 \Rightarrow 2 Ethanol + \underline{2 CO_2} + 2 ATP$

Aerobes take in as much gas molecules as they excrete, while anaerobes (the ones producing ethanol at least) only make gas.


Finding phylogenetic distance between sequences? I'm working on a piece of software that does comparative genomic analysis; and I found out in homology methods for functional annotation, it's preferable to pick the high scoring homolog from a distant sequence (i.e. not closely related to the query sequence in the phylogenetic tree).  My question is: why? and also could NCBI taxid for each taxon be used for approximating this distance? if not, then is there a simple way of making this binary decision (close, not close) when given two sequences.

No, because it is really not a binary decision. There are attempts to associate percent pairwise difference with taxonomic ranks (particularly species), but this is problematic because every independent lineage can vary according to its own rate. You could use sequences from different families, or orders, or even phyla, but these two can depend on whether specialists in the field are lumpers, or splitters. For example, all ants are in the same family, and Formicidae is over 100 million years old, while birds that may have diverged from a common ancestor within the last 10 million years are in a different family. You can use pairwise distance OR higher-level taxonomy as a proxy. But it would be crude. Why not program your software to make hard decisions about homology, and then find the closest most distant homologue in terms of pairwise differences?


Advantage of opponent color? Opponent process is a color theory that states that the human visual system interprets information about color by processing signals from cones and rods in an antagonistic manner (source).

What is the advantage of opponent color against RGB color? For example, in object recognition or edge detection?

Can we say that it provides some level of invariance to changes in brightness?

RGB color is a more direct representation of the "raw input" received by the (human) eye, since the three types of cone cell have responsivity spectra that roughly correspond to red, green, and blue light:

Opponent color decomposes color into three "dimensions" of opposing properties: dark or light, yellow or blue, and red or green.  This provides some brightness invariance, since changing the intensity of light will change the brightness but not the yellow/blue or red/green balance of the color, even though the stimulation level of all three types of cone cell will change.

One could speculate that opponent color perception is more "meaningful" in real-world environments.  The dark/light axis represents the overall amount of light, the yellow/blue axis indicates which end of the visible spectrum is predominant, and the red/green axis provides a finer distinction for low-frequency light.


Activated carrier molecules and their relationship to enzymes I am reading Molecular Biology of the Cell, and one thing I don't quite get is the difference between an enzyme and an activated carrier molecule. I understand that enzymes lower the activation energy for a reaction, and in that sense speed up the rate at which a reaction occurs. I also understand that activated carrier molecules act as a source of energy that can drive unfavorable reactions (like anabolic reactions) forward. But I still don't quite grasp the exact difference. I was wondering if someone could shed some light on this.

I will focus on the meaning of ‘activated carrier molecule’ as descriptions of enzymes abound. In order to do that I need to introduce two other ideas first. I apologize to the purists for tailoring this to the level of the question.
1. Gibbs Free Energy in Biochemical Considerations
There are different ways of considering energy, and in chemistry one may be used to considering bond energy in relation to a particular molecule. However in biochemistry (which is what this question is concerned with) the focus is on the energetics of overall processes. For example “Are the reactions involved in the synthesis of glucose from pyruvate energetically favourable?" or “How can the synthesis of glucose from pyruvate occur if the overall reaction is not energetically favourable?” Likewise for individual reactions, such as the formation of peptide bonds between amino acids.
For considerations of this sort the thermodynamical concept (Gibbs) Free Energy (G) is most useful. This is because the change in free energy (ΔG) during a reaction (or other change of state) indicates whether a reaction can occur spontaneously. To quote from a useful section in Berg et al.

A reaction can occur spontaneously only if ΔG is negative.

So in the reaction sequence just mentioned, the overall synthesis of glucose from pyruvate (gluconeogenesis) has a positive ΔG and is energetically unfavourable, whereas that of the reverse process (glycolysis) is energetically favourable. And likewise peptide bond formation, not surprisingly, has a positive ΔG and is not energetically favourable.
2. How are Energetically Unfavourable Reactions Accomplished in Living Cells?
The question posed in the heading arises from the fact that gluconeogenesis and peptide bond formation occur in living cells, even though taken alone the core reactions that represent the processes are energetically unfavourable. The answer is given in the title of [section 14.1.1. of Berg et al.]

A Thermodynamically Unfavourable Reaction can be driven by a Favourable Reaction

As already stated, it is the ΔG of the overall process that is important, so if a reaction with a positive ΔG is ‘coupled‘ to one of negative ΔG of greater magnitude, the overall reaction can proceed. For example:
A → B           ΔG =  20 kJ/mol (unfavourable)
C → D           ΔG = –30 kJ/mol (favourable)
A + C → B + D   ΔG = –10 kJ/mol (favourable)

If reaction C → D proceeds alone, the free energy is liberated as biochemically useless heat. If it is coupled to reaction  A → B it drives the latter with the balance being lost as heat.
3. The Role of Activated Carrier Molecules in Energy Coupling
Clearly, any coupled reaction can cause water to run uphill, as it were. But in order to continue one needs to regenerate the starting molecules for the favourable reaction. It is more efficient to specialize this regeneration process by using a limited range of specialist reactions with a negative free energy change. One description of the substrates (reacting molecules) of such specialized favourable reactions is “activated carrier molecules”. Alberts et al. define them as:

Small diffusible molecules in cells that store easily-exchangeable energy in the form of one or more energy-rich covalent bonds. Examples are ATP and NADPH.

Berg et al. also use the term, but describe it in terms of the following examples:

ATP as an activated carrier of phosphoryl groups, because phosphoryl transfer from ATP is an exergonic process (i.e. has a negative ΔG)
Nicotinamide adenine dinucleotide (NAD+) is a major electron carrier in the oxidation of fuel molecules. (Although in this case it is the half reaction involving the oxidation of the reduced form, NADH — or NADPH as mentioned by Alberts et al. — that has a negative ΔG).
Coenzyme A… is a carrier of acyl groups (but it is the transfer of the acyl group of acyl-CoA molecules — e.g. acetyl CoA — with the generation of CoA that has a negative ΔG).

Examples of the participation of such molecules in metabolism can be found in the volume referenced, however I would emphasize that it is the specific reactions of these molecules involving the groups (or electrons) that they carry that is important.
And what about Enzymes?
As the poster stated “enzymes lower the activation energy for a reaction”. They are (generally) large proteins catalysts that have no effect on the ΔG, and they are unchanged at the end of the reaction.
Of course they are important for biochemical reactions, they participate in them, and provide binding sites to bring the substrates and activated carriers in juxtaposition so that they can react. But they couldn’t be more different from the small activated carriers.


Randomness in living systems The point of my question is not to talk about events that are uncontrolled by living organisms. My question is about controlled randomness, or I'd like to say adaptive random process. Process that are random because it was selected in order to be random.

The first thing that pop in my mind when thinking of "adaptive random process" in biology is Fair Meiosis. Do you have other examples of "adaptive random process"? An individual might display a random behaviour in order to avoid that others to predict its future behaviour. Is there any evidence for such things? Do you know any other evidence on what I called "adaptive random process"?

In an evolution mutations are often random and lead to differences in phenotype that can be adaptive under certain pressures.  A lot of times mutation is a random process, but here are three cases I can think of off of the top of my head where I would say the organism is 'trying' to do it:

HIV is a retrovirus, which means in its viral form its genome is single stranded RNA, which is then converted into double stranded DNA within the host.  That conversion is carried out by a virally encoded reverse transcriptase.  This enzyme has a much higher error rate when making the RNA into DNA because it cannot proofread like our DNA polymerases.  This means that HIV mutates incredibly fast.  Many of these mutants are not very fit, but since there is so much selective pressure against staying the same due to attack from the immune system, some mutants will be much more fit if they can avoid that attack.  Its a numbers game, and by making lots of random mutants HIV is very good at it.

A related, but different case is found in the diversity generating retroelements of certain bacteriophages.  These are double stranded DNA viruses that infect bacteria.  The bacteria these viruses infect could mutate to escape the viruses by losing a certain receptor that the virus binds to.  It was observed however that the the virus would mutate incredibly quickly to bind to a different receptor, a lot faster than would be expected for a DNA virus.  Also, it was found that these viruses contained reverse transcriptases, which is bizarre, since there is no reverse transcription step in a dsDNA viral life-cycle (so we thought).  To make a long story short, this virus will transcribe the DNA that codes for its binding proteins into RNA, then use its reverse transcriptase to turn that RNA BACK into DNA, but uses a sophisticated targeting strategy so that it only mutates the region that is used for binding to the bacteria.  It will only mutate adenine residues, leaving the C's, T's and G's alone.  This is a much more clever system than HIV, because this virus uses site-specific mutations on its binding feet, and doesn't mutate its core proteins, the mutation of which would probably just lead to viruses that couldnt replicate.  Here a reference for the interested: http://www.nature.com/nature/journal/v431/n7007/abs/nature02833.html

Just so you dont think this is reserved to viruses, we do this as well with our immune system.  In order to recognize antigens in attacking pathogens, our immune cells have two methods for making diverse, random, receptors.  First is V(D)J recombination, where the multiple diverse copies of the V, D and J regions of antibodies and receptors are combined at random to make one set.  Wiki says theres 3x10^11 possible combinations here.  After that, theres also somatic hypermutation during the proliferation of B cells.  In this process, the random mutation rate is hugely increased in the region of the B cell receptor gene, specifically for making slightly different versions of the already 'OK' receptor to make it a great receptor.

General theme: raising your mutation rate, either across the board(HIV) or specifically (DGRE and SHM) is a good way to intentionally add randomness for a beneficial purpose (to the extent that you can attribute 'intent' to a viral particle).


What is a selective constraint? I encountered the term selective constraint in Huber et al. 2015, page 4 (last paragraph) in:

  If invariable  sites are included in the   analysis, then both the methods of
  Kim   and Stephan (2002)  and Nielsen et  al. (2005)  may be  sensitive
  to    assumptions regarding selective constraint  and mutation rates.

but the context does not quite help.

What it the definition of selective constraint?

Does it has to do with lethal mutations in non-coding regions? Does it has to do with selection interference?...

It is selective pressure that determines and limits the number of neutral/beneficial mutations that can take place. The more constrained a locus is under selection, the easier it is to generate deleterious mutations and the harder it is to generate beneficial ones; this can be reflected in low substitution rates at such loci in populations with time.

One widely used method to measure this is to compute the Ka/Ks ratio to infer if a locus is selectively constrained or not.


Glucose 6-phosphate dehydrogenase: reaction mechanism I have searched the internet for the reaction mechanism of G6PD but couldn't find it, so I am asking whether anyone here knows its mechanism and whether they could recommend some sources that give detailed info about enzyme mechanisms generally.

I would be grateful for this because it seems difficult to find enzyme mechanisms on the internet.

Disclaimer

I am not an enzymologist and this answer is based on work published in 1998, and the latest paper I consulted was 2000. Hence I cannot exclude the possibility that more recent work has modified the model shown here.

General Approaches

The general approach to elucidating the mechanism of action of enzymes has been as follows.

Historically, and before a structure is (or was) available:

Hypotheses of possible types of mechanisms would be made on the basis of the known mechanisms of non-enzymic chemical reactions.
Experiments with inhibitors might suggest what class of residues of the enzyme might participate in the reaction.
Experiments would be performed to get indirect evidence for the residues involved, e.g. by examining the effect of pH in relation to the pKa.

More recently, with structure determination less difficult and more common:

The structure would be determined and an attempt to identify the active site made on the basis of the position of a bound pseudo-substrate or inhibitor.
Residues near the substrate that might participate in the reaction would, thus, be identified.
A hypothesis of the role of these residues would be made in relation to the known chemistry (as in historical 2, above).
Experiments would be performed to test the participation of the residues — often by modifying them — and their proposed role.

Proposed Mechanism for Glucose 6-phosphate dehydrogenase

The structure of glucose 6-phosphate dehydrogenase (G6PD) was published in 1994 by Rowland et al. in Structure 2:1073-1087. To test their hypothesis of the mechanism, Cosgrove and coworkers constructed performed site-directed mutagenesis on G6PD and determined the structure of the mutated protein. On the basis of this they published a paper in Biochemistry 1998 37:2759–67 in which they proposed the reaction mechanism shown below.

The Nδ1 atom of His-240 is hydrogen bonded to the Oδ1 atom of Asp-177, forming a catalytic dyad. The Nε2 of His-240 is poised to act as a general base by abstracting a proton from the C1-OH of G6P, allowing transfer of the C1-hydride to the C4 position of the nicotinamide ring of NAD(P)+.

They summarize this as follows:

  “The results support a mechanism in which His-240 acts as the general
  base that abstracts the proton from the C1-hydroxyl group of glucose
  6-phosphate, and the carboxylate group of Asp-177 stabilizes the
  positive charge that forms on His-240 in the transition state. The
  results also confirm the postulated role of His-178 in binding the
  phosphate moiety of glucose 6-phosphate.”

Suggested reading and search approach

The classic text on enzyme mechanism is Alan Fersht’s Enzyme Structure and Mechanism published in 1984. This is clearly based on a limited range of enzymes, so its importance is not in finding the mechanism for a particular enzyme, but for understanding the principles involved. (You can pick up a second-hand copy very cheaply). Fersht has a more recent (2017) book in the same area — Structure and Mechanism in Protein Science but this is much more expensive. You can view the contents on Amazon.

Other suggestions are welcomed as comments.

My approach to searching for an answer here is worth mentioning as the question indicates the poster failed in his attempt. First I just did a Google search “reaction mechanism, glucose 6-phosphate dehydrogenase”. This wasn’t very useful, but alerted me to the fact that Google was prioritizing pages related to G6PD deficiency, a clinical condition on which much had been written. To avoid this I decided to focus specifically on structure, assuming that some of the papers would be proposing mechanisms. I tried three of the following four approaches (while idly waiting for a computer program to run).

Google search on “glucose 6-phosphate dehydrogenase, structure”. This did not appear to give me a direct hit, but brought up the three other sources I went on to try.
The Wikipedia entry on glucose 6-phosphate dehydrogenase. Half way down the page is a section on structure with a diagram of the substrate binding site, so I knew I was on track. The references on this page were not very useful, but the diagram indicated the structure was PDB 2BHL.
The Google search also brought up a Protopedia page, which I actually looked for directly. At first I was disappointed by the lack of information other than the structure, but the third of three references was a Cosgrove paper from 2000 which contained the words “catalytic diad” in its title. I went for that, and it led me back to their 1998 paper.
I could have tried the Protein Data Bank and searched for 2BHL (or just for the enzyme). 2BHL would have led me to a later paper in Acta Crystallographica, which does mention the 2000 Cosgrove paper in its introduction.


How to determine the height/bits in a sequence logo? I am trying to create a sequence logo, and I am completely confused by how to determine the height/bits for each column. So, for example I understand how to create the flat sequence logo: (add up all the letters, the letters should represent their ratio for that position) but not the normal sequence logo:.

I have been reading this paper "WebLogo: A Sequence Logo Generator" again and again and I can't figure out how to determine the bits/height for each given position.

Wikipedia has a page on sequence logo which discusses the calculation briefly.

The "bits" here are related to those used in Shannon entropy. This is an information-theoretic equivalent to the Boltzmann entropy from thermodynamics. This is a measure of how "disordered" the position is, or more precisely how specific the distribution is.

The general formula for the total entropy (expressed based on probabilities/fractions) is

$$ S = -k \sum_i p_i \cdot log( p_i ) $$

where $i$ ranges across all the various states (e.g. each nucleotide).

The difference between Shannon entropy and Boltzmann entropy (aside from the contexts where it's used) is the value of the constant (one for Shannon, Boltzmann's constant for Boltzmann entropy) and which logarithm used (the natural logarithm for Boltzmann entropy, and typically base-2 for Shannon entropy.) As it uses base-2 logarithms, the Shannon entropy is typically measured in units named "bits".

The wrinkle is that the entropy of a distribution isn't really what you want to display in a sequence logo. Instead, you want something that gets larger (not zero) when the sequence becomes more defined. As such, the values displayed are not the entropy itself, but the "entropy loss" from a completely random (maximal entropy) distribution.

That's how you get the total number of bits at a position (the total height). The height of the individual letters comes by taking the total height and multiplying it by the probability of each state. This might not have rigid theoretical justification (you can't attribute the entropy loss to individual nucleotides like that), but it fulfills the display purposes of making the more prevalent nucleotide identities larger in display size.

For example, if you have a position with 70% G and 30% C, then you have
$$ (4 \cdot -0.25 \cdot log_2(0.25)) - (-0.7 \cdot log_2( 0.7 ) + -0.3 \cdot log_2( 0.3 )) = 1.12$$ bits of total height. G gets a height of $1.12 *0.7 = 0.78$ bits, whereas C gets $1.12 *0.3 = 0.34$ bits.


Capture recapture for only two visit assuming a open population model I have a study system where I’m doing a capture recapture analysis. I mark fish in one year and I’m recapturing a subset of them the next year.

I only have 2 capture events. Since a lot of time has passed, relative to the fish, between the two episode of recapture, I cannot assume a closed population model. Is there an alternative?

What mark-recapture model would be best for this situation given that I want to compute a recapture probability?

In a classic closed population model, you can estimate population size with k=2 (where k is the number of events) but it's impossible to separate survival from recapture probability.

Seeing this formula you could expect to be able to estimate recapture probability dividing R by S but it would be an error since S = M*survival (ø) *probability of recapture (p) . Therefore it's imposible to separate p from ø when k<2.

Hope it helps !

Cheers


What is this strange mantis-like coral reef dwelling creature? On the first episode of BBC's Blue Planet II they visited a coral reef and showed some odd reef-dwelling creatures as part of their establishing shots, but did not name the creatures.

In particular creature that resembles a mantis:

I tried a Google reverse image search and it very 'helpfully' identified it as "Documentary film". So close, yet so far.

The specimen is indeed a mantis shrimp (to be specific, a peacock mantis shrimp).

These predators have highly sophisticated vision and, depending on the species, either spearlike limbs or clubs that move so fast the water can't keep up, causing dangerous cavitational effects that can even break glass.


Assessing beta diversity variations with time I'm just starting in the field of ecological statistical analysis and I have a few doubts regarding a dataset that I'm working on.
The dataset is composed of several samples collected at a single location during a few months multiple times per day.
From my data I have estimated the beta diversity (Bray-Curtis dissimilarity) and I'd like to know if there is a monotonic trend with time and how much of the diversity can be explained by the different sampling hours or days.
My questions are the following:
- Is the estimation of Mantel's Rho using Spearman correlation is a valid estimator for the linear temporal trend?
- To estimate the source of the diversity (days/hours) would it make sense to run a npmanova analysis (as I'm using R I'd run adonis in particular) using as explanatory variables the sampling hours and dates?

Rather than Mantel, I would suggest doing a procrustes analysis. I didn't know much about it (and still I don't) but a reviewer required it for a paper I submitted, so I used the implementation in vegan package. You can also give a look at this nice tutorial
The idea of procrustes is similar to Mantel's but it should perform better for this case.
I don't what to say about the second question, sorry!


Why does hypocalcaemia cause increased muscle contraction? Calcium is needed for  muscle contraction, so how does hypocalcaemia cause increased sustained contraction?

Consider the pathophysiology of tetany, which is the involuntary contraction of muscles caused by hypocalcemia.

From the tetany wikipedia page:

  Low ionized calcium levels in the extracellular fluid increase the permeability of neuronal membranes to sodium ion, causing a progressive depolarization, which increases the possibility of action potentials. This occurs because calcium ions interact with the exterior surface of sodium channels in the plasma membrane of nerve cells and hypocalcemia effectively increases resting potential (rendering the cells more excitable) since less positive charge is present extracellularly. When calcium ions are absent the voltage level required to open voltage gated sodium channels is significantly altered (less excitation is required).

So, when Ca2+ levels are low, action potentials are spontaneously generated, leading to muscle contraction.


What are the most important factors influencing a person’s gut microbes? You are your bacteria! The probiotics and the antibiotics...

There has been on going discussions about how our gut bacteria is important for a healthy lifestyle.

  Figure 1: Schematic diagram illustrating potential or known mechanisms
  whereby probiotic bacteria might impact on the microbiota. These
  mechanisms include (1) competition for dietary ingredients as growth
  substrates, (2) bioconversion of, for example, sugars into
  fermentation products with inhibitory properties, (3) production of
  growth substrates, for example, EPS or vitamins, for other bacteria,
  (4) direct antagonism by bacteriocins, (5) competitive exclusion for
  binding sites, (6) improved barrier function, (7) reduction of
  inflammation, thus altering intestinal properties for colonization and
  persistence within, and (8) stimulation of innate immune response (by
  unknown mechanisms). IEC: epithelial cells, DC: dendritic cells,
  T:T-cells. For further details, see main text.

Also, an online search provides numerous articles about diet aspect that alters our gut bacteria.

e.g.

1.A New Diet Quickly Alters Gut Bacteria-(not sure about the credibility and relevance to humans as the study is on mice)

2.Artificial Sweeteners Change How Our Gut Bacteria Work, Paving The Way To Diabetes And Obesity

3.Changing gut bacteria through diet affects brain function

As far as the GIT is concerned, health, lifestyle, eating habits and the environment a person is living may be at large influence and affect one's gut microbes.

Are there day to day encounters, in-depth examples and references that can prove the factors which influence our gut microbes the most?

Our Unique Microbial Identity (Gilbert 2015) suggests that the gut microbiome is shaped and stablized during infancy and tends to restore equilibrium if it is disturbed later in life. Antibiotics temporarily change the composition of the gut microbiome (by suppressing the growth of certain groups of bacteria more than others), but it tends to drift back to resemble its original (stable) community after treatment is stopped, likely due to the interdependency of individual strains as producers/consumers of particular compounds (i.e., some bacteria will eventually arrive to serve a particular role in the microbial community). A recent study in antibiotic treatment provides some empirical evidence of the long term effects of antibiotic treatment on the human gut microbiome.

The American Gut Project is currently open to the public for participation, and it has the goal of identifying exactly the factors you describe. They are accepting samples from individuals across the country, along with lifestyle information, including dietary habits. A related publication by the group provides a summary of the common gut bacteria implicated in a variety of diseases.

H. pylori infections are a common gut microbiome health issue. This bacteria is present in about half of gut microbiomes and are not generally harmful unless the stomach lining is already compromised (e.g., due to medication or diet). In those cases, they can become opportunistic pathogens that can persist for decades and cause peptic ulcers which can lead to a variety of difficult to diagnose ailments such as arthritis.


Does the lack of "mirror life" tell us anything about abiogenesis? My (extremely rudimentary) understanding of Biology is that many of the building blocks of life are chiral and that life on earth is entirely made up molecules with the same chirality.

Does this have any interesting repercussions for our understanding of abiogenesis?

EDIT:
Just to be clear I am interested in understanding how life developed from non-life (on Earth in particular and, more speculatively, in the universe broadly). For instance, the article linked in Matt's answer that it may be due to the polarization of light in our area of the galaxy is very interesting.

I see several (not necessarily exclusive) hypotheses (and probably am certainly missing some) about the asymmetry of the chirality of existing lifeforms of and was wondering if there was any sort of consensus (or at least informed speculation) on which was more likely or less.

Abiogenesis is an incredibly rare phenomena and so the opposite chiral life never developed.
Which every chiral form of life appeared first and this prevented the formation of the other chiral form of life.
There is some sort of selection principle that selects for the chirality we appear.
If simple versions of life and mirror life occur simultaneously it precludes or retards the development of complex lifeforms (A sort of anthropic principle).
``Mirror life" is not actually possible--there is some subtle phenomena that requires the chirality we have on Earth.
Something else...

As far as I know, there isn't too much we know about why life is "left-handed". So far the prevailing hypothesis is that in space there may be a tendency for amino-acids to favor one chiral-state over another, and there's some very smart people who are testing this, as opposed to the 50:50 shot here on Earth.

To answer your question, however, the general consensus is that life came from non-living
material. Pan-spermia, intelligent design, and the rest are more fringe ideas, so the question is how life formed from non-life. One of the ideas is that the basic building blocks came from space (likely a comet or meteor), and if the idea that amino acids favor one chiral direction over another in space can help support that hypothesis.


Image Dataset for Cardiac cells for Mus musculus? I'm working on developing a transfer learning model to detect cells in a culture using microscopic images.
for that i require data set of images having microscopic images of various cell types. Is there any such database present? Any open source research work having  microscopic images of cardiac cells that can be used?

Sure help yourself with the broad institute image sets collection

Broad Bioimage Benchmark Collection - Annotated biological image sets for testing and validation:
https://data.broadinstitute.org/bbbc/image_sets.html

And the EMBL-EBI:
https://www.ebi.ac.uk/bioimage-archive/

No mouse cardica cells, but I am confident you can easily do transfer learning after training on those.


Why are successful human rock climbers so dissimilar to Hominidae primates who spend extended time periods climbing? In rock climbing, the sport considers the Ape Index when evaluating the factors critical for success.

However, the majority of successful climbers are lithe and slim with less than 8% body fat.  As one professional described it

  “I feel very pressured to be thinner for climbing. I’m very strong, but I will likely never be thin, and I think that it holds me back…I don’t have that classic thin, long-limbed climber body…”

However, this seems completely at odds with the primates that we see on documentaries and in zoos which appear to be heavy, muscular, powerful and with considerable upper body strength.

Professional human climbers, while strong, rarely have significant quantities of muscle (Bodybuilder-esque) on their skeleton. They seek a power to weight ratio through weight-loss.

What accounts for this difference in development?  How do primates move such heavy masses through the upper canopy and why have they not evolved slimmer, smaller or more lithe frames?

As a rock-climber myself I’ll attempt to answer:  The selection criteria for competitive rock-climbing is exclusively based on sustain non-resting, extremely challenging moves up a rock-face.  The two most challenging aspects are 1) ability to ‘crimp’ (climbing term) on micro-holds without slipping and 2) being able to keep that up without resting throughout the climb.  I personally have a real problem with the later, because of my weight.

Primates selection criteria is not isolated to non-resting climbs.  They don’t get penalized for sitting on the branch.


Identify this thin and strangely-shaped dragonfly, and understand why the shape looks so weird I took these photos around noon in mid August in Hsinchu county Taiwan. I've seen many dragonfly varieties but I've never seen anything like this before.
Its body is about 5 cm long and very thin compared to the ones shown in the related questions below. The midsection looks strangely shaped to me, as if it is bent upwards in the back and suddenly ends, and a very thin "tail section" was then added below it.

This dragonfly damselfly is from the species Pseudocopera ciliata. Dragon fly anatomy changes between species and there is not definitive answer for why it looks like that, the best guess i can give is that it may assist the female as she tries to find the hookup point for mating.
General Information
More Information(Pay-wall)
This is in Chinese but confirms presence in Taiwan: http://gaga.biodiv.tw/new23/s3-37.htm


Does 405 nm light set off phosphorescence in the eye? While playing with a blue/violet laser (5 mW, 405 nm) tonight, I noticed that on dark, non-fluorescing surfaces, the beam reflection was trailed by what looked like a dimmer reflection of the beam. The effect was most easily observed when I moved the laser in a circular motion. The apparent 2nd reflection was not produced by a side lobe of the laser diode, as it always trailed the main reflection, regardless of clockwise or counterclockwise rotation. Also when I stop moving the beam, the second 'reflection' quickly merged with the main beam reflection.

I doubt it is caused by phosphorescence of the material (cloth) I was lasering, as it also showed up when I pointed the laser at the floor, other sorts of cloth and painted walls.

So, do rods, cones, visual purple or other eye components phosphoresce when hit with deep blue light?

Instead of phosphorescence, a more parsimonious explanation is the perception of afterimages. Afterimages regularly appear after viewing a bright stimulus. They occur in the same location in the visual field as the original stimulus, but lack clarity. Afterimages depend on the intensity and contrast of the original stimulus (i.e., they are more pronounced with bright stimuli in a dark environment), the time of fixation (i.e., longer fixation generate more persistent afterimages), and retinal adaptation (i.e., dark environments enhance afterimages).

After images are almost always the complementary color (negative afterimage) to the original stimulus, but can very briefly be the same color (positive afterimage) when viewing an exceptionally bright stimulus. A stimulus consistently produces the same afterimage, which varies in size based on the distance between the person and the background. After images are often revived by blinking.

Afterimages are thought to derive mainly from photobleaching of the retina, although cerebral processes may contribute too.

Phosphorescence in the retina has to be induced by injecting phosphorescent markers (Wanek et al., 2013). As far as I know, the retina is not autophosphorescent.

References
- Gersztenkorn & Lee, Survey Ophthalmol, (2015): 1-35
- Wanek et al., Curr Eye Res (2012); 37(2): 132–137


Why is beta- D fructofuranose two different structures when in free form and as part of sucrose? This is the structure of fructose in free form:

The right moiety is the fructose as part of sucrose. The left one being glucose:

Both of the fructose are beta-D fructofuranose. But as it can be seen they both are clearly completely different structures. The anomeric hydroxyl group seems to be in an opposite position while the rest of the structure hasn't even changed shape.

Where am I getting this wrong. Thanks.

I'll try to explain this to you, but you should really look it up here: https://pubchem.ncbi.nlm.nih.gov/compound/beta-Levulose#section=3D-Conformer&fullscreen=true

This is the structure of beta-D-fructofuranose, as a 3D conformer. On paper, or as a 2D figure, we cannot visualize the -OH groups at positions 3 and 4.

They appear to be inside/outside the ring, but in reality, they're not really positioned that way. Both the -OH groups are oriented in an opposite manner, but in a plane perpendicular to that of the furan ring.

So when we flip it over to represent it in sucrose, the orientation of the -OH groups in the molecule flips too.

Think of it this way: if you have a piece of cardboard  (representing the ring) with a pin pierced into it (representing the -OH), and you flip the board over, the pointy side of the pin will face down too.

Moreover, if we represent it this way, the absolute configuration of the side chains at each of the carbons of fructose remain the same.
You could check that using their RS configurations.

For more on RS configurations, check out : https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_(Organic_Chemistry)/Chirality/Absolute_Configuration%2C_R-S_Sequence_Rules


What is this spider from Arizona? I live in Phoenix, Arizona, USA. Can you please identify this spider for me. Is it dangerous?

It's hard to judge from a single photo but it appears to be from the Family Theridiidae (cobweb spiders). Spiders in this family have long front (first legs)and much shorter third legs as the spider in your photo seems to have. But the perspective may be off. You don't mention the size which would help.

I enjoy photographing insects and spiders in my area. One thing I found when I was trying to identify spiders is colour and pattern can vary quite a bit from different locale. Sometimes two spiders of the same species could look like two completely different species.

So please bear this in mind. All I am is an arthropod enthusiast that has benefited from some more skilled and knowledgeable people helping me out. With that in mind, I wonder if your spider might be Phylloneta pictipes (syn. Theridion pictipes).

Source: http://bugguide.net/node/view/2209

I should've said but the two spiders above are the same species; male on the right and female on the left.

You can check out more spiders of this species at http://bugguide.net/node/view/49080/bgimage and see how they vary.


Do cancer cells give off specific chemical signatures? Do cancer cells give off specific chemical signatures?   Are these signatures different from normal cells?

The answer is it depends.  First, take a step back from the definitions of "cancer" versus "normal" cell and recognize that cells and tissues can undergo a variety of changes in their growth.  A solid cancer/tumor (as its usually defined) is something that grows and invades the surrounding tissue.   A spectrum of possible cell growth can be :

normal -> hypertrophy -> hyperplasia or dysplasia -> hamartoma -> benign tumor -> carcinoma in situ -> invasive cancer -> metastais

(this list is NOT suggesting these are the actual steps to cancer, but instead they are useful for the next paragraph):

The point of this list is that from a human perspective we can see something odd happening when we see a tumor, but the view from inside a cancer cell is basically "things are fine, I'm just doing my cell thing".

But, that said...when a tumor grows and cancer cells invade tissues a few things happen which can give rise to differences between cancer cells and normal tissues and which can be detected.
First, it needs energy, and cancer cells often switch to aerobic glycolysis (a phenomenon called the Warburg effect). As the link shows, a special form of labelled glucose can be used to detect this in the body.

Secondly, a tumor invades the surrounding tissue and generates new blood vessels, and so enzymes that break down extracellular matrix  are released.

Some tumors over-express and secrete markers (usually proteins) that can be detected.  The prostate specific antigen (PSA) and carcinoembryonic antigen are two examples.

Other things secreted by certain tumors may include volatiles that can be detected by dogs.

The challenge with any 'signature' detection is the sensitivity and specificity  which often limits the use of tests that show some early promise.

Cancer cells DO have specific changes to their DNA that can be used as very specific signatures for detection.  Tumor DNA is shed into the blood and possibly the urine.

Finally, tumor biology overlaps with many aspects of normal biology, including wound healing and pregnancy and this continues to make it challenging to identify tumor specific markers that have high sensitivity and specificity.


If everybody DNA is different then how blood can match even with matching blood group? We know that everybody's DNA pattern is different in the world. Then how can ´we transfer blood from one person to another person and this person can survive ?

A few components to my answer.

Red blood cells do not contain a nucleus, therefore, they do not harbour DNA.
The major determinant of blood compatibility is the blood antigen. There are only 4 types: O, A, B, AB. This is genetically encoded, and is expressed as a set of sugar coats on the blood cell membrane. However, the enzymes that encode for A or B should be identical from person to person.

I hope this gives you a preliminary answer to work off.