CharonY

Yeah, he was (never seen in him in person, just interviews) and certainly one of the greatest voice actors.

Not sure why but this little tidbit stuck with me: in "What's opera, doc" Arthur Bryan was Elmer's voice ( "Ritt der Walkueren" is forever linked to "Kill the Wabbit" in my brain) . Two years after release Bryan died and was buried in Valhalla Memorial Cemetery.

I have no idea what a video would do as data would be static (e.g. final titer or growth rate). A gradient on a plate would not tell you much either, as up to lethal temperatures all you would see is that the colonies are smaller as they start growing more slowly. But I can tell what you are going to expect. Depending on the bacteria, you will see increase in growth rate up to their optimum temperature and then a decline and finally death. In other words, you won't see nice inhibition zones as for antibiotics. For many environmental bacteria the optimum is around 30C. For those living on warm blooded organisms the temperature is unsurprisingly close to body temperature (e.g. ca. 37C for most mammals, but ~40-42C in many birds). Whether they are pathogenic or not is of secondary relevance. However, some of these bacteria also have heat resistance genes, often acquired by mobile genetic elements which allow them to survive for several minutes in temperatures up to 80C. While there is not a lot of evidence that those provide any benefits during infections (in case of pathogens), they were increasingly found in food-borne bacteria, where they survive sterilization efforts.

That's interesting, in my lab we were taking sensitive wild-type strains and try to figure out which 'regular' metabolic functions are required to proliferate under sub-lethal concentrations.

Good points, though I would add that in contrast to resistance, susceptibility is a rather difficult concept. For the most part it is more the absence of a resistance mechanisms than a proper trait in itself. Beyond that, the ability to deal with antibiotic stress is highly dependent on factors such as nutritional status. I.e. a strain on minimal medium will be much more susceptible than in rich medium. Mutations associated with higher susceptibility will likely also result in lower viability and/or competitiveness.

That is absolutely correct. There is much overlap on many of the mechanisms involved (e.g. nutritional acquisition, surface attachment etc.), though a rule of thumb is that if it is detrimental to the host we start thinking of something as an infection. As usual in biology, the boundaries are not fixed, and due to certain conditions (immune system issues, tissue injuries, but potentially also nutritional shifts etc.) otherwise benign bacteria may actually colonize areas where they start to do harm (i.e. they become opportunistic pathogens). To me, it is always interesting that in medicine we have these seemingly clear boundaries and treatment options, whereas the buggers themselves do not particularly care about them. There is this huge overlap between commensalism, beneficial symbiosis an parasitism with vastly different outcomes, but often fundamentally related mechanisms. That being said, it is important to recognize differences when they matter, such as when thinking about treating infections.

It would ultimately depend on the mechanisms involved in the condition. But I do not think that we know enough about it to make a prediction. Which basically means that one would need an empirical study to look at it.

You could entertain yourself by educating yourself about what an infection is, and how antibotics resistances work. And apparently you also do not know what a non-infectious bacterium is, which indicates you probably do not know the difference between pathogens and non-pathogens. Of course you are repeating yourself, you simply have no information to improve your posts. You are also not reading what folks are telling you, as you just keep repeating and presenting your limited understanding of microbes. I am not sure what else to do than telling you that your basic premise flies into the face of basic microbiology there is simply not much to add. Before I stop this futile exercise: what, do you imagine is a mechanism of antibiotics sensitivity? And how about you tell me at least one method of resistance?

Yeah, I lost my nerd license to my wife, so I know how it feels.

And part of it is also not understanding language. Being infected and being colonized are two different types of events and have specific requirements. And could talk about cases where the difference between benign and harmful bacteria start to blur but that is a different discussion (though quite an interesting one).

I think you'll have to return your nerd license and re-apply.

Well, as usual it is about what kind of cuts you are making. The conservatives complain that the overall cuts are not enough i.e. they were not massive. However, those that are affected by cuts are going to complain about those that are made. I understand that you were making a joke, but as a whole nuance has gone out of the window, it seems. Too often such statements are taken at face value for the sake of soundbites, influencing serious decisions. It remains a fact that as a whole the budget does not seem significantly different than what the previous government proposed, which could mean that there is not a whole lot that can be cut. And among things that are cut, one needs to look at long-and short term costs. Cutting public health funds, for example could save money now, but if, say disease monitoring and prevention is compromised, you may look at a huge bill in the future. Other investments, such as better food programs for low-income children, have been associated with surprisingly significant savings later on due to reduction in welfare costs. As a whole, however, I would say that the Canadian election has shown less divisiveness than what we see in other countries. The largest number of votes went to the centre-right and centre-left parties whereas the further right PPC failed. Contrast it to the rise of far-right parties of Europe, or look at the state of the conservatism in US, which basically has to bow to a TV personality, I think it is still in a decent shape. Of course there have always been the conflict between say Western and Atlantic Canada, or the fact that the Prairies are often overlooked (or feel like they are), which certainly causes resentments. These have recently been massively fueled by social media and other new ways of communication, but again, in comparison as a whole Canada is holding it together somewhat well.

So, what's up, doc?

This refers back to the basic issue that you simply fail to understand basic microbiology. An infection is caused by a pathogen, a specific bacterium able to cause a disease. If you put a non pathogenic strain out there that happens to be sensitive, how does it result in the rise of a sensitive pathogen? Is it an existing pathogen that somehow loses its resistance in presence of a sensitive strain (there are no realistic scenarios where that could mechanistically happen, but it may not be obvious if you do not understand what antibiotics resistance actually is), or is it because the sensitive strain does the infection? That is the only possible route based on your own description, if a sensitive strain outcompetes other bacteria, including pathogens, what is there but those new strains to infect? However, a truely benign strain would not be infectious. Of course, if you actually sprayed folks with high titers, they may actually become dangerous. And of course nothing prevents those magic strains to actually acquire resistances (remember, Hypervalent iodine trying to tell you about acquired traits?). And of course as everyone is also trying to tell you, it is impossible to replace microbiota with an artificial strain short of disinfecting every living being and the complete environment on top, which basically would collapse the whole ecosystem. It is just so monumentally, mindboggling silly, but apparently there is not way in to make you see that (as it would require to learn a bit about bacteria and other microbes in the first place).

But here is the thing, while he did run on such a platform, but apparently in the 2018-19 fiscal year the PC government spent more than the proposed budget by Wynne (sure you could make the argument that they would have blown that one, too) and even according to conservative think tanks such as the Frasier institute they were massively overspending (and now promise to balance after the next election). And I would again note that debt is not fundamentally bad, depending on interest rates and how it is spent (e.g. if they help generate surplus in the future). But since that is a difficult subject with many nuances that probably needs an expert, we may as well skip it for now. I think that both provinces suffer from the strong reliance on natural resources, their debt seems to be tightly coupled to resource prices which basically means that if debt is the critical element, government actions will be dictated by external forces. I do not think that this is a sustainable model for the future.

That part (especially regarding antioxidants) is quite incorrect. For starters, it is true that the immune system does not react to very small molecules (say metal ions) but it is not that they only react to cells (which would exclude viruses in any case). Rather they react mostly to antigens, which are generally somewhat large(ish) molecules. These can be proteins or lipopolysaccharides, for example. The immune system does play a role in combating toxins, too (especially the humoral immunity). For example, antidotes against venom are generally antibodies raised against a particular venom. Antioxidants themselves do not calm cells down, rather they react with free radicals. While there is data out there that suggests that antioixidants may actually increase immune functions (some suggest that they stabilize immune cells and/or prevent their aging) there is fairly little in terms of hard evidence that a diet rich in antioxidants has a significant impact on overall health (or at least whether the benefits are really from the antioxidants, but rather due to other aspects of such a diet).

Very simple. Go and read up on mechanisms of antibiotics resistance it would also help to look at, say bacterial replication. After you read it, think a little bit what selective breeding of a weaker strain would actually mean. Specifically how can you ensure that there will be susceptible pathogens to infect people with? You also seem to have a problem in realizing the difference between pathogens (who infect folks) and the regular microbiota (who mostly don't). Obviously, if you create sensitive harmless strain, you seem to believe that it somehow can spread to pathogens. The issue is that you do not quite understand how little you understand about microbes and that seemingly prevents you from noticing the why, fundamentally, the idea makes no sense. It was shown that just highlighting the mechanisms that you fail to understand is insufficient to make you see the issues. The only alternative is to provide a short lecture on microbial genetics but since that would most likely fall on deaf ears, I am not sure how to proceed. There is simply no foundation to build on that I can see. Many points have already been made regarding how resistances arise and spread as well as that it is almost impossible to fully replace existing microbiota (and the fact that we all carry resistant strains with us already). Or that we have far more reservoirs than you believe and so on.

Actually no, it a commonly used term in global cycles to describe reservoirs which accumulate and store a given compound (carbon in this case). Any sufficiently large body can act as a carbon sink (regardless of rain) as CO2 exchange with the atmosphere only happens at the surface. If the water is cold, more CO2 is dissolved than released, if it heats up again more CO2 is emitted (ignoring biological fixation for now). As such, deep cold bodies of water can act as a net carbon sink. The paper by Li et al. (i.e. the one referenced by OP) have found that dissolved inorganic carbon also be sequestered into enodrheic basins. A important mechanism that was observed is that CO2 from soil is being dissolved in the highly saline (and alkaline) water into groundwater aquifers and transported to a terminal lake. The salinity is an important element here as the higher alkalinity allows increased CO2 solubility. They found that source water (i.e. rain snow melt etc.) were basically carbon free, but the groundwater was high in dissolved carbon. That showed that during the transport of water to the basins, they dissolved singificant amount of carbon along the way (i.e. we have mechanism often described as carbon pump into the mentioned carbon sink). Carbon dating experiments showed that the dissolved carbon most of it was fairly young, resulting from soil respiration. Similar mechanisms have been proposed for other terminal lakes and I found a follow-up paper that escaped my notice earlier: Li et al. Nature Geoscience volume 10, pages501–506 (2017)

Well, it looks like that Canada is headed for a Liberal minority government. Edit: cross-posted.

Bacteria also freely mutate on their own. That would be bacteriophages and they are already in use. Phage therapy has been used since the Soviet Union. However, they have a lot of limitations, including the fact that they are highly targeted and have narrow uses. But there are more issues, which is why antibiotics have become so successful when they were available. They are getting now a revival because of the rise of resistances. However you generally would not want just to try resistance, as there would be no point to it. If phages were to reverse resistance in some strains, there would still be selective pressure to acquire resistance. So in order to suppress you would need to flood the patient with more phages and more antibiotics, which is not really a good therapy.

What is a 'twitter'?

I should also clarify why I said it was bad. To be precise, it is also dangerous. While there are strains out there that are considered to be safe, we do not actually know if we put them in high concentration somewhere where they should not, e.g. due to inhalation. Opportunistic pathogenesis can arise under these conditions, which is really bad news.

There is not a huge difference as far as lab strains go. Due to the fairly permissive situation in the lab the strains are not competitive. What you would need to do is recreate a bacterial community for almost any possible surface and reservoir. How would that happen? Unless you spread AB-sensitive pathogens around (and get arrested for bioterrorism). Sensitivity is not a particular trait that spreads around. Nope, everywhere where you can find antibiotics you select for those bugs. These include wastewater, manure and basically everywhere they end up, ranging from soil to water sources. This is why the current situation has become so dire. It again implies something that is competitive. In a given environment. Unless you want to smear everything with a biofilm, which again is a horrible idea. If only because you cannot prevent the strains put out not to acquire or become resistant. Look, you need to know the basics of resistances. Some of which require a simple point mutation. You cannot breed that away, bacteria are not cattle. Even if we only think about more complex systems, such as efflux pumps, what is going to happen is that the existing traits will spread including through your artificial population (assuming they manage to persist a significant time frame), creating a brand new reservoir of resistances. It is simply a bad and unrealistic idea.

I think there are burgeoning studies trying to find neural correlates of psychopathy. The issue with these (typically neuroimaging) studies is that there is a high risk of spurious association of findings with a pre-defined conditions. That being said, there are a number differences in found in folks considered to be psychopaths. If those structures are indeed relevant to the condition, it is likely that the reaction to relevant signaling molecules may also be altered. For example, resistance to oxytocin could be related to psychopathy-related traits. Actually, I believe I may have seen studies looking into that, but cannot really recall any details off the top of my head.