arachnology - What species is this large-ish spider?

Last night I came across this spider outside my house (costal Southern California). It was bigger than any I'd seen before, about 2.5 or maybe 3 inch legspan, maybe just under an inch for the body length. It is a brown-gray color, the cephalothorax has two dark brown stripes, and some mean looking fangs. Can anyone identify it?

Cell Respiration and Oxidative Phosphorylation

The passage of protons through the F_O (membrane) portion of the molecule (driven by the electrochemical gradient of protons across the respiratory membrane) generates torque at the interface between the a and c subunits. This mean that the ring of 10 c subunits rotates relative to the a subunit. The γ subunit in the stalk rotates along with the ring of c subunits, while the ring of α and β subunits in F₁ is constrained to remain static with respect to the a subunit because of the interaction with the δ and b subunits (forming the peripheral stalk). So we have two portions of the molecule the "static" a-b₂-δ-α₃β₃ part and the rotating c₁₀-γ-ε part. The γ subunit rotates within the α₃β₃ part of F₁ and drives a three-step cycle of conformational changes (via intersubunit interactions) which are linked to the phosphorylation of ADP.

There is a useful animation here illustrating the three step catalytic cycle being driven by the rotation of the γ subunit.

(image from Aksimentiev et al. (2004)
Insights into the molecular mechanism of rotation in the F_O sector of ATP synthase. Biophys J. 86:1332-44)

neurotransmitter - Do SSRIs downregulate or upregulate the 5-HT3 receptor?

SSRI's theoretically increase Serotonin levels. Serotonin is an agonist to the 5HT-3 receptors. The 5HT-3a primarily associated with the upper gut and the 5HT-3b with the lower gut. I would guess that theoretically again, SSRI's would tend to increase nausea, emesis, and diarrhea. There may be other effects, but these are the ones I have researched.

The anti-emetics Dolasetron, Ondansetron, Granisetron, and Tropisetron are 5HT-3 antagonists.

evolution - What evolutionary pressures pushed Galápagos tortoises to mature so slowly and live so long?

This isn't so precisely focused on tortoises, but a general theory in evolutionary biology for why some animals live longer is K vs r selection theory.

The idea here is that animals will make a sort of evolutionary 'choice' and configure themselves to breed as numerously and quickly as they can. This is called 'r' selection, named after the constant that is proportional to the rate or speed of breeding. r selected animals adapt quickly to a rapidly changing environment and their lives are pretty cheap. Many insects that lay hundreds or thousands of eggs every few weeks are examples of r selection. They do not care for their offspring (and may even eat them!).

K selected animals breed to be highly competitive in the environment. They tend to be highly optimized for success and this often means they are larger, they live longer and require more investment as newborns.

By this theory the galapagos tortioises live longer because their environment changes very slowly and the tortoises are so optimized for that particular way of life that they have no predation or any competition at all. Islands like the Galapagos are studied in fact because they are so isolated by the water that new species rarely ever arrive. Such new arrivals may cause drastic changes in their ecosystems because islands are stable environments because migration happens so rarely.

There are other theories that emphasize other factors in the evolution of larger, longer lived animals, but I think r/K selection may describe the environmental pressure on the Galapagos tortoise.

genetics - Two brown-haired people have two children, P and Q. P has blond hair. Q has brown hair. What is the probability that Q is heterozygous?

Assumptions: Blonde hair is Homozygous Recessive and that the traits are strictly Mendelian.

The parental generation must be both heterozygotes as at least one child is Blonde (bb). So your cross is Bb x Bb.

Your square is going to look like this:

           _B_            _b_

_B_         BB           Bb



_b_         bB           bb

So of the question is:

What is the probability that Q is heterozygous?

The PhD is INCORRECT. They probably just made a simple Punnet Square in their head and forgot the caveat that you have to exclude "bb" because Q is not Blonde. The possible allele combinations for non-Blonde offspring from a Heterozygotic cross are only BB, bB, Bb.

Therefor the probability that Q is Heterozygous is indeed 2/3 (bB, Bb).

It's not uncommon for PhD students - who are often deep into their own research - to gloss over details and possibly give incorrect answers because the information hasn't been relevant to them for years (most traits aren't Mendelian, strictly recessive or dominant, and rarely involve a single allele), so give them some slack unless they were being a jerk about it. =)

neuroscience - Are there any types of cancer that cause neurons to divide?

I think that most mature cells do not divide in all tissues. If organism need to repair tissues, it uses tissue cell precursors -- stem cells.

In case of neurons, these are neuroblasts. Neuroblasts can divide and can repair brains under some circumstances (I don't know under which).

There is a cancer grown from neuroblasts, called neuroblastoma.

I think it is very unprobable to have tumor from neurons, because division gens are turned of in mature cells. Can't state it is not occurring in practice.

evolution - Why are there exactly four nucleobases in DNA?

Here is a possible answer given by this paper:

http://www.ncbi.nlm.nih.gov/pubmed/16794952
or
http://www.math.unl.edu/~bdeng1/Papers/DengDNAreplication.pdf

It gives a Darwinian explanation to the question. It approaches the problem from Claude Shannon's theory for communication. It treats DNA replication conceptually and mathematically the same as a data transmission. It concludes that the system of four bases, not two, not six, replicates the most genetic information at the shortest amount of time.

The communicational analogy goes like this. If you have two data transmission systems, one can transmit, say, 1 MB per second, and the other can do 2 MB per second but cost less than twice as much. The answer is obvious you will buy the second service for a higher rate per cost. As a data service, it does not care what information you consume -- it can be spam, video, audio, etc. All that matters is the transmission rate. As for DNA replication, it is like a data transmission channel when one base is replicated a time along the mother DNA template. It too does not care whether the process is for a bacterium genome, or a plant, or an animal genome. The pay-off is in information and the cost is in time. Unlike your abiotic communication varieties, time is both the sender and the receiver of all messages of life, and different life forms or species are merely time's cell phones. So if one system can replicate more information in a unit time than another, the faster one will win the evolutionary arm race. A prey operating on a slow replicator system will not be able to compete with nor to adapt to a predator operating on a fast one.

Now because the A-T pair has only two weak hydrogen bonds but the C-G pair has three, A and T take a shorter time to complete duplication than the C and G do. Although the replication time is short in some fraction of nano second, but the time adds up quickly for genomes with base pairs in the billions. So having the C-G pair may slow down the replication, but the gain is in information. One base pair gives you 1 bit per base information. Two pairs gives you 2 bits per base information. But, having more base pairs may eventually run into a diminished return in information replication rate if the new bases take too long a time to replicate. Hence the consideration for the optimal rate of replication measured in information bits per base per time. Without information there would be no diversity, no complexity. Without replication in information there would be no life.

Using a simple transmission/replication rate calculation by Shannon you can calculate the mean rate for the AT-system, the CG-system, the ATCG-system, and for some hypothetical 6-bases, 2n-bases system whose new bases take progressively longer time to replicate. The analysis shows the ATCG-system has the optimal replication rate if the CG bases take 1.65 to 3 times longer to replicate than the AT bases. That is, a base-2 system replicates its bases faster but does not carry more information to have a higher bit rate. Likewise, a base-6 system has a greater per-base information but replicate slower on average to end up with a suboptimal bit rate.

According to a comparison from the paper, the base-4 system is about 40% faster than the A–T only system, and 133% faster than the G–C only system. Assume life on Earth started about 4 billion years ago, then the A-T only system would set back evolution by 1 billion years, the G–C system would do so by 2.3 billion years. For a hypothetical base-6 system, it would do so by 80 million years. In other words, life is where it should be because the base-4 system is able to transmit information through the time bottleneck at the optimal bit rate.

In conclusion, life is to replicate the most information with the shortest time, and the base-4 system does it the best. If ever there were other systems they would have lost the informatic competition to the base-4 system from the get-go. Darwin's principle works at life's most basic and most important level.

There are other explanations, all non-Darwinian. Most are based on the base's molecular structures. But these types of explanation border on circular argument -- using observations to explain themselves. They also face this catch-22 problem since there is no way to exhaust all possible bases for replication. However, such lines of exploration are fruitful regardless because more knowledge the better. But without taking information and its replication into consideration it is hard to imagine a sensible answer to the question.

synthetic biology - Has anyone ever sucessfully translated xRNA or yRNA?

I've recently been researching the subject of size-expanded nucleobases in alternative genetic sets. Many papers describe the, at least, partial success in replicating xDNA and yDNA, as well as transcribing them, as suggested here.

At the same time, studies on polymerase replication and transcription of oligonucleotide sequences reveal that chemical entities other than the typical nucleoside triphosphates can be tolerated to varying degrees.

My question is can the cell's molecular machinery, including ribosomes and tRNA, possibly lead to translation of xRNA or yRNA? Would the translation product yield the traditional 20 amino acids? Have this ever been attempted?

References to original papers would be appreciated. Thanks!

human genetics - Is there any difference in terms of personal healthcare between complete DNA sequencing and SNPs genotyping?

This difference would have the greatest impact on treatment for cancer, in which a treatment protocol is based on genes deleted, amplified, altered in the tumor vs the reference genome for that patient.

In terms of health risks based on SNP genotypes, the data are far from complete. Sure, some level of risk can be assigned to a variant (SNP), say at certain markers within the FTO gene and risk of obesity. However, the complete list of risk alleles for this and numerous other complex traits is not fully described. Furthermore, the impact of environmental factors (EF), or lifestyle choices, on those genetic variants is only beginning to gain wider attention. For example, a risk allele may not show itself as risk until the EF, such as amount of physical activity or percent energy from dietary polyunsaturated fat, passes a certain threshold. Such gene-environment interactions are thought to contribute to the variance in traits (phenotypes), but to what degree is not known.

Added in edit 15 May 2012: Epistasis, or gene-gene interactions, also are important but far from being cataloged for humans. A situation could arise where one allele elevates risk for a certain condition, but compensatory alleles elsewhere in the genome decrease that risk. We don't know the full extent of epistasis in humans.

Thus, in terms of personal healthcare outside of something like cancer and monogenetic disorders, there may be little that is gained from genotyping or complete genome sequencing, little that is compared to other advice you already know. I carry risk alleles for certain conditions, but there is not really any advice one can give me that is specific for those alleles that I have, where that advice is different than or goes beyond general advice health care providers already have dispensed.

neurobiology - How do we get used to smells?

As Ben Brocka mentioned, what you're describing is Habituation, which Wikipedia defines as:

Habituation is a decrease in an elicited behavior resulting from the repeated presentation of an eliciting stimulus (a simple form of learning.

More specifically, it's technically called Neural adaptation. To quote Wikipedia again:

Neural adaptation or sensory adaptation is a change over time in the responsiveness of the sensory system to a constant stimulus. It is usually experienced as a change in the stimulus. For example, if one rests one's hand on a table, one immediately feels the table's surface on one's skin. Within a few seconds, however, one ceases to feel the table's surface. The sensory neurons stimulated by the table's surface respond immediately, but then respond less and less until they may not respond at all; this is neural adaptation

As this was explained to me in Psychology 101, this is the same phenomenon which allows us to not feel our shoes shortly after putting them on. It's also what enables people to perform really dirty, smelly jobs like sewer maintenance and garbage collection.

The process works exactly as you described, and many people can instantly relate to it: The longer you are exposed to a given stimulus (like a smell) the less you continue to react to the stimulus. The stimulus becomes more "normal" to you, and you start to think of it less. As soon as the stimulus is removed, the effect begins to reverse. The Characteristics of Habituation section of the Wikipedia article covers this.

protein folding - A question regarding evolution

Since we only have one planet that we know of with life, it's a bit difficult to make good estimates on the probability of various events in the history of life. To make a good estimate, you'd want to have thousands of planets very similar to earth to compare. Since we don't have access to that kind of data, one proxy which you can look at is how long did it take for some event to happen in earth's history. In a vacuum you'd expect things that took longer to happen to be rarer. From this point of view, it seems likely that the development of multi-cellular life from simpler life forms is a low probability event because it took 3 billion years of simpler life forms before it happened.

Another way to get information on probabilities is to look at widely separated branches of the tree of life. Since wings evolved separately in birds, bats, insects, and pterosaurs, the probability of wings evolving in a planet with a similar atmosphere and multicellular animals is likely pretty high. Similarly, you can argue that the development of human level intelligence is relatively low probability because it has only developed once in the history of the planet in one lineage that very nearly died out. Dinosaurs never developed human level intelligence, nor did rodents, or mollusks, or arthropods. On the other hand, it seems that a lower level of intelligence at say the dog level is relatively high probability (since it has evolved separately in mollusks, birds, mammals, etc.).

synthetic biology - What can cause incompatible sticky ends to be ligated?

Actual question

I have reason to believe (details see below) that in a ligation I carried out, an EcoRI sticky end (EcoRI: G'AATT_C) and an XmaI sticky end (XmaI: C'CCGG_G) were somehow ligated together, a process during which at least the EcoRI site was lost: the plasmid had a BamHI site very near the XmaI site, and a BamHI/EcoRI digest produced only one band compared to three bands in the undigested control (three conformations of circular plasmid).

How could ends as incompatible as EcoRI and XmaI be ligated?

Detailed Background or: Why I believe incompatible sites were ligated

This is chronologically further to: What are common causes of unexpected ligation products?. Briefly: I digested two plasmids, one with EcoRI and XmaI (p1), the other with EcoRI and AgeI (p2) [XmaI and AgeI produce compatible sticky ends], then carried out a ligation between a 1.4kb insert isolated from p2 (structure EcoRI-1.4kb-AgeI) into the 3.4kb backbone isolated from p1 (structure XmaI-20bp-BamHI-3.4kb-EcoRI). After transformation, I tested the ligation product by digest with EcoRI and BamHI, which should produce again 3.4kb + 1.4kb. The gel was poor quality but allowed the conclusion that there were different ligation products.

Repeating the EcoRI/BamHI digest and gel more carefully showed there were only two variants: Variant A (8 colonies) produced the two expected bands 3.4kb and 1.4kb. Variant B (4 colonies) only produced a clear 3.4kb band, nothing else visible in the lane: in other words, it only carried either an EcoRI or a BamHI site and was in total smaller than variant A (confirmed by undigested controls). Thus, I conclude that B was simply the same 3.4kb backbone, re-ligated without the 1.4kb insert. Since the BamHI site was untouched in the backbone during the preparatory EcoRI/XmaI digestion, I assume that the EcoRI site was not recovered during the ligation of variant B.

(The ligation was carried out overnight at 16 deg C, using Promega T4 DNA ligase and buffer and a molar ratio of 3:1 insert:vector at a total volume of 20uL. The E.coli for transformation were Invitrogen OneShot Stbl3 and have been routinely and successfully used in the lab for a long time. The analytical digestion used Promega EcoRI and BamHI in Buffer Multi-Core, which Promega claims offers 75-100% efficiency for both enzymes. Incubation was 1.5h at 37°C.)

endocrinology - Are serotonin levels in humans affected by light?

I'm reading this Wikipedia article on light therapy and noticed a peculiar statement:

The production of the hormone melatonin, a sleep regulator, is
inhibited by light and permitted by darkness as registered by
photosensitive ganglion cells in the retina. To some degree, the
reverse is true for serotonin, which has been linked to mood
disorders.

If I read this correctly, when melatonin is suppressed, serotonin is released? This makes some sense. I'm interested if there is any scientific backing to serotonin being affected by light levels.

evolution - What's the Evolutionary Purpose of Religion?

In terms of genetic evolution, religion itself cannot really be considered to have an evolutionary advantage or disadvantage, as it is not anchored in any genes. This means that it is not an evolutionary trait and hence the principles of evolution do not apply to it. However, religion is a product of underlying capabilities of the brain (for example imaginative capacity?), and these are genetic and evolutionarily advantageous. Aside from this, asking for the 'evolutionary purpose' of anything is the wrong way to approach the topic, as things do not evolve to have a purpose but they simply evolve and stick around unless they produce a net disadvantage compared to a competing version of the same trait.

You could look at religion from a memetic point of view however, i.e. as an idea which competes with other ideas. The idea of religion has many aspects to it that would help it to 'survive', i.e. not be forgotten. These include the drive to tell other people about it, ease of understanding, the claim of exclusivity, addressing many social cravings, and filling in gaps of knowledge for which explanations are desired.

mitochondria - Why do brain cells use shuttles that pass electrons from NADH to FAD?

In the absence of unanimous consensus and sources regarding the actual distribution of these shuttles,(wikipedia favours G3P shuttle abundance) let me try to explain the cause if the glycerol-phosphate shuttle is assumed to be prominent in brain cells. Several possible reasons might lead to this:-

1) The existing metabolic pathways are all intertwined to form a complex metabolic net. This means that invariably, the intermediates of any pathway are the products or intermediates of several other pathways. Therefore, the G3P shuttles require Glycerol-phosphate and Glycerol-phosphate dehydrogenase (I and II) which might be naturally abundant in brain owing to its use in strict lipid metabolic control in nervous tissue. This means that tapping the already high G3P for use as a shuttle compared to synthesising and operating a distinct metabolic shuttle is more profitable. Furthermore, operating Malate aspartate shuttle migh require intermediates whose high concentrations (required to maintain the shuttle) might negatively interfere with existing metabolic pathways like protein synthesis and regulation.

2) This shuttle has much faster operation time than Malate-Aspartate shuttle and hence is very useful in shuttling reducing equivalents fast in muscles and brain. Compared to the malate aspartate shuttle, it is shorter and hence faster and less prone to cessation due to unavailable intermediates or enzymatic disruption. Due to several enzymes working in Malate-aspartate shuttle, it has a narrower pH and temperature optima than the G3P shuttle which is shorter and depends on lesser intermediates, and hence is less prone to disruption.

3)The last and the most far-fetched (but relevant)reason is that the loss of one ATP may not cause much of a problem because of already high respiratory rate, high Oxygen delivery to brain and ability of the body to quickly transfer available energy sources to brain at the cost of other parts, at times of energy stress. This means that replacing the shuttle with a more energetically conserving one may not have a strong driving force for evolution to operate on, and therefore the presence of G3P may be because of something like phylogenetic inertia, that is, the prevalence of an ancestral character just because it is neutral and does not influence the fitness in a considerable manner. Therefore, the ancestral G3P shuttle would just not have been replaced here but this is very unlikely as G3P shuttle is prominent in 2 very high energy-demanding organs, muscles and brain.

Except the last outrageously far-fetched reason, all other reasons should be enough to explain its prominent presence (if it is true) in brain tissues.

Studying changes in DNA for causes of cancer

I tried to comment but what I wrote is too long, so here it is as an answer of sorts.

If I understand the question, you are asking: has anyone done a prospective study where they store the DNA of individuals and then later, when some of these individuals get cancer, have a look for mutations that are associated with that cancer. In fact this is done all of the time, but it isn't necessary to store any DNA because the cancer patients will have the normal sequence in all of their non cancerous tissues - only the cancer cells will have the relevant mutations. See here for a recent example of this type of study that made the news.

Your BBC link is to a story in which the genomes of people will be analysed to determine if there are genetic factors which predispose them to cancer (and other diseases), but these won't be the mutations that actually create the cancerous cells.

genetics - What is the role of hippo signalling in oral squamous cells

Mutations in the Hippo signalling pathway cause unusual organ growth in flies. After a good deal of intensive research, its been shown that Hippo genes are responsible for suppressing organ growth in development, increasing cell death and slowing proliferation.

Given this role, its not surprising that Hippo genes are also important in cancer. I'm not an expert in cancer, but a quick search turned up an association of cancer with the Yki (YAP in mammals) transcription activator, an oncogene from the Hippo Pathway. YAP suppression has been linked to cancerous growth. And its also been shown that YAP is amplified in oral squamous cell carcinoma cells. This last is circumstantial but consistent with what we know about YAP.

How much food can an average person eat, and which animal is that equivalent to?

When the average person overeats, how much food can he eat in a day? Which animal's average meal would that be equivalent to?

When documentaries are talking about animals feed, they usually say something like "The fish can eat 500kg of prawns in a day!" But when it comes to humans, they calculate in calories. Which animals are we closest to in terms of capacity?

Note: I think I can be slightly loose on the definition of overeating here. It can mean eating beyond the point of feeling full, or the human maximum stomach capacity.