CharonY

I can see no scientific basis for the any of the assertions. The similarities provided in the examples are crude at best and certainly share no structural similarities. Certainly speculations material.

How about a shorter term after election (as evaluation time so to say), followed by a longer one after that?

Everything ajb said. Note that the hard part is AFTER getting the PhD. Neither passion nor degree will guarantee you a career. It is more that once you realized what it entails, without passion there is no good reason to go through all the post-degree madness.

Technically all human cell lines are considered to be potential risks (and hence BSL2), mainly due to presence of viruses. The well-known HeLa carries HPV, for example. However, the actual risk are relatively low. They viruses are generally only found in low concentrations (if at all) and a small droplet is not likely to do much. In fact, if you work long enough with them and are not careful there is a big chance that you inhaled more during pipetting (when not working under a biosafety bench), centrifugation, or other aerosol-generated processes (which you should not, but with many people working in a lab you never know). Lab safety is all about preparing for the worst, and it is good that you are aware of potential risks. But again, the likelihood of immediate consequences thereof are minuscule. You should report the event, however, to have it documented regardless.

Without looking at those and reference chromatograms (values are too arbitrary to be looked at without reference points) and a look on reproducibility one cannot say too much about it. The peaks could e.g. be contaminations, especially if they show up at the same time. But again, not enough info to troubleshoot.

I have issues with that. It assumes there is some kind of homeostasis within our body and/or cells. However, aging is progressive (think of cell maturation, for example). There is no phase that I could think of where there is a homeostatic condition resulting in "normal gene expression" (I also have no clue what that is) and hence, no aging (for a while, at least). This simply does not agree what we know about cell development and aging, for example (i.e. progressive mitochondrial damage; telomere length and telomerase activity, etc.). With an erroneous premise, further deliberations are not likely to be accurate.

A classic setup was three oil baths and an undergrad.

Indeed. Although I do think that they may actually have physiological consequences of sorts. For example, such stretches may affect DNA dynamics and in a subtle way alter gene expression strengths. Although this is more likely of relevance for single-celled organisms and the evolutionary consequences are likely to be of more relevance.

Well, the question is what the physiological consequences of these are. Large genomes offer an enormous "habitat" for mobile genetic elements (or, one could argue that they became so large because of them). As the size and structure are somewhat less under selective pressure than in bacteria they may offer quite a different landscape for evolutionary changes. Early analyses of the human genome estimated something close to 45% of the human genome consist of transposable elements (and much higher levels were found in plants). However, their mechanism of replication is quite specific and chances are that an alien virus would not be able to do much.

1. Only the first methionine is recognized as starting codon (in bacteria, formyl-metionine is actually incorporated at the onset of translation). Further AUG are treated (for the most part) as regular methionine. A simplified way to visualize this is that the ribosome is formed at the ribosome binding area of the mRNA, the mRNA is then pulled through until the start codon is recognized. From there the elongation of the protein is processed normally, until it is terminated. In some cases (mostly viral genomes) genes can be stacked. In this cases a second ribosome binding site can be found within a larger coding area so that the initiations starts further downstream. 2. The implications can be quite deep. To understand some of them, one has to know that the genetic code is realized by the presence of tRNA that carry a specific aa with a respective anticodon, which recognizes the particular sequence on the mRNA. So mechanistically each codon requires the presence of their respective tRNA. I.e. a tRNA carrying the respective anticodon, coupled with a given amino acid (phenylalanine in this case). Some implications: - protein synthesis can be controlled by tRNA levels. One particular tRNA may be present in low concentrations, for whatever reasons, and genes carrying their codons may not become (fully) translated. - mutations within each codon can result in different amino acids (not so much an issue in this example), likewise, mutations in the genes coding for the respective tRNAs will result in different effects (as these are different genes) - on a similar note, different bases (uracil vs cytosine in this example) have different propensity to mutate in presence of different agents, so mutation rates may differ

Yes, something else is likely to be needed, but not necessarily of viral origin. I was thinking if intracellular parasites in general. Bacteria are an interesting example (think in terms of mitochondrial-nuclear gene transfer). The precise mechanisms are afaik unknown, however.

Basic text books are your friend. Either general biology (such as Campbell) or specialized genetics books (Lewin for example).

The article describes retrotransposons as a source of horizontal gene transfer, something that has e.g. also been described in Drosophila. The actual mechanism is still unknown, but hypotheses include parasites as vectors (including e.g. bacteria). Wolbachia is an example (again, with Drosophila). Retroviral transfer is a more classic route (though not the subject of the paper in question), but would not be considered terribly novel, I would think.

I am not quite sure what the question is, but hemosiderin occurrence is linked to ferritin, in fact it appears a metabolized form of ferritin. As such it is a means to reduce intracellular free iron. The source of the iron does not play a major role in this regard, i.e. neither the ferritin molecules nor the responsible regulators do not know where the rise in iron content comes from. The reason why it is being linked to Hb degradation in certain textbooks is that hemosiderins are often found in macrophages and in these cases a plausible source is the degradation of red blood cells. However, it is only one example to describe the situation where hemosiderin may be observed and is not the biochemical pathway leading to its formation per se (nor its biological role, for that matter).

Also one should be asking whether e.g. you envision an academic or private sector career. Fundamental research is mostly in the academic area. But usually there are only few pure research positions there.

Yes, most animals have reduced anabolic amino acid pathways. Apparently there was no selective pressure to maintain the respective genes and subsequently we lost the ability to synthesize them.

That is interesting. If they manage to deliver on that we may reconsider our current instrument road map. It would take some convincing, though, as some early adopters were badly disappointed.

The shotgun approach is not dependent on restriction enzymes, although they can be used. More often than not mechanical disruption is used to obtain less biased fragments. Even if you can sequence over a specific area with repeats (i.e. have sufficient read length) base calling (identification of the correct base) can be an issue as repeats tend to generate results with resolution. IIRC PacBio has pretty much abandoned strobe sequencing (in favor of the RS system with a few kb read length). I am not sure whether they go a grip on the accuracy issue, though.

The stability of a peptide also depends on its tertiary structure. If the peptide is not denatured, proteases may not be able to access the cleavage sites. Also it depends a bit on how you assess whether there was proteolysis or not (e.g. searching for fragments or indirectly via activity assays). Peptides may retain biology activity to some extent, even after cleavage. I have not read the paper but looking at the sequence there are quite a few cysteins (allowing for disulphide bonds). Moreover they generally do not ionize well and yield low signals in MS, which may limit identification of fragments. But in addition we see a number of hydrophobic residues, such as tryptophane and tyrosine, so my guess (without any close analysis) is really that tertiary structure may inhibit cleavage.

Actually no. A properly constructed study looks at relationship and does not set out to find a particular one. As such studies are not supposed to have intentions. Of course there may be researchers biased towards a particular outcome, but the idea of a good design is to prevent any influence in that regard. I think Hemenway made a good point about the overestimation of the effects, especially as they managed to reproduce the results but added a control to demonstrate that there is likely a severe flaw in it. This is a point that Hemenway specifically addressed by asking whether the assailant was wounded. The resulting numbers were a clear overestimation.

Ah, well maybe on the website. The studies (papers) themselves are a bit better and usually the conclusions are also formulated in a much more careful way. To me it does not actually mean that the authors were biased towards the outcome, but they would rather not acknowledge a faulty methodology in their study. There are a few correlation studies that looked into whether right-to-carry laws have any influence on crime rates. The consensus appears to be that the data does not support any correlation between RTC laws and crime (in some cases an inverse correlation was observed). (Aneja et al AMERICAN LAW AND ECONOMICS REVIEW Volume: 13 Issue: 2 Pages: 565-632 DOI: 10.1093/aler/ahr009 Published: FAL 2011)

I am not quite sure what you mean. I assumed you initially provided the link from the Kleck study? But as I mentioned, it appears to be a statistical error due to the low numbers problem. There are further studies that apparently look at specific relationships and also may have corrected for this error (it does not appear to be a finger pointing issue or manipulated data at this level). But I would have to read a bit more, when I got some more time (there a lot of them around, judging from abstracts the effects seems to have vanished in newer studies). I should add that many of these studies may suffer from certain issues in the estimation methodologies and models. That is also addressed in a number of studies.

I would have to read through the website (despite the hideous color scheme), but are there peer-reviewed studies supporting the assertion of that website (especially as they do not present references in a convenient format), It should be noted that the Kellerman et al. paper is based on a regional sampling, a nationwide (comparative) study could probably provide more global insights. Edit: found a paper (Armed resistance to crime: The prevalence and nature of self-defense with a gun Kleck, G; Gertz, M: JOURNAL OF CRIMINAL LAW & CRIMINOLOGY Volume: 86 Issue: 1 Pages: 150-187 DOI: 10.2307/1144004 1995) The findings are apparently somewhat controversial. Kleck and Gertz estimated a number of 2.5 million defensive gun uses per year between 1988-1993 based on a telephone survey (with n=5000). This number was faced with scepticism as estimates of crimes committed firearms were estimated to be around 1.3 million per year. Hemenway and others have looked into this, and it appears that these kind of surveys may result in an overestimation of effects. They have, for instance, conducted a similar survey which yielded slightly lower but still roughly the same results. However, with follow-up questions they also estimated how many attackers were wounded or killed during these defensive actions The surprising result was that the the number was roughly the same as the total amount of gunshots (fatal or not) reported. Yet almost all of the reported number were due to accidents, suicide or criminal assault (i.e. not a defensive gun shot). Likewise, based on the survey data the authors estimated that 322,000 of the defensive cases were to thwart rape attempts. Again, a number higher than the total number of recorded rapes and rape attempts. A reason is that the survey tries to identify a rare event (defensive gun shot) and thus even small false positives can massively distort the estimates. (see Journal of Policy Analysis and Management, Vol. 16, No. 3, 463-469 (1997))

Best bet is to look at the websites of companies related to your field (maybe biotech or analytical labs, for example) or use job websites. Job fairs are also a good way to get industrial contacts.

If you are thinking with regards to an academic career, the outlook is bleak. The only real stable position is becoming a tenured professor (there are also positions in private and national labs, but they are so few that one should not plan on getting them), meaning that between teaching, getting funding and leading a lab you will have little time for actual research. However, less than 20% of all PhD holders will eventually get tenure. How to land a job? In the end it depends on a heap of luck (you can tweak chances to your favor, but not just by being a good scientist). It depends on whether you happen to work on a project that is a hot topic. It depends on whether your PI during your PhD/postdoc has the interest and power to further your career. In other words, many factors that are not in your power contribute to it. The reason is that there is a huge surplus in capable scientists, and nowadays it is almost impossible to distinguish yourself on your own. In short, degrees do not land you a job, contacts and networks do. Just to give an idea, after PhD you are going to become a postdoc, which, depending on the lab (and country) often involves working on several projects, leading grad students, some administrative work and sometimes teaching. Generally around 4 years are expected in biological sciences then you are supposed to find a faculty position. Problem is that most will not get it (as mentioned) and if you hang around for longer it actually reduces your net worth. Depending on area your likelihood of getting interviews drop after prolonged postdocs. So you technically have a somewhat narrow (though depending on your work often flexible) window to make a transition to faculty. After that (if you are really lucky and have networked like crazy) you may become an assistant prof (or equivalent) and you are tasked to lead a lab, teach classes, doing administrative work (on faculty level) and get funding in. At this stage getting money is usually one of the main criteria of actually keeping the job (i.e. getting tenure). The funding rate of the big agencies such as NIH are somewhere between 2-10%. So if you do not get money after 5 years you may get your tenured denied. At this stage you may be around 40 and out of a job. Chances of getting a new shot at tenure are low as the new generation(s) of academics are now on the tracks. In other words, if you want a stable and secure career with clear progression, academia is not for you. It is a highly competitive field and there is no clear path towards a career here. You really have to want that life, otherwise it is really not worth the stress.