7 ms·

Biophysicist here. Excellent questions – these are the kind of points peer reviewers would raise (though typically in far more esoteric and passive aggressive w

Biophysicist here. Excellent questions – these are the kind of points peer reviewers would raise (though typically in far more esoteric and passive aggressive ways...). (1) could be addressed in experiments where the algae-consumers in question are studied in monoculture (purified and grown in test tubes) with virus added artificially. This experimental design excludes the possibility that any middle man is present; if uptake is still observed, it must be direct. (2) Measure viral replication, perhaps in a similar monoculture experiment as above. If the viruses are infecting (exploiting) the Halteria, they will have non-negligible replication (they are stealing the Halteria's resources to advance their own replication). Viral replication could be assayed by qPCR (counting viral genomes) or similar assays. (3) This would require biochemical studies to determine the mechanism of uptake of viral particles. Typically, viruses are taken up (endocytosed) by cells as a result of interaction with receptors on the surface of target cells (prominently CCR5 in HIV, Ace2 for the COVID-19 causing virus). Of course, what biological systems are `trying` to do begs that we anthromorphize Halteria (or at least evolution), but one could conduct an evolutionary analysis to see if Halteria have progressively evolved receptors that improve viral uptake efficiency. As an aside, the discovery of virovores hints excitingly (albeit remotely) at the possibility of creating virus sink cells/technologies that could eliminate viral particles in humans. An important question will be whether viruses, which evolve far faster than eukaryotes like Halderia (let alone than humans), can turn the tides in the evolutionary arms race and become the exploiters of the Halderia. Perhaps it's reassuring that we exist (mostly) symbiotically with our microbiota, despite their far faster evolution.

panabee 4y ago
great answers to great questions. 1. the parent raised questions in a neutral way. these questions seem essential for validating experimental design. why would peer reviewers present such questions in passive-aggressive ways, and how can we fix this? 2. could you kindly recommend services/consultancies to validate experimental designs? if not, would you be open to consulting and doing what you did here -- suggesting ways to control for key variables? experiments relate to cancer research. contact info in bio.
- KRAKRISMOTT 4y ago
  > 2. could you kindly recommend services/consultancies to validate experimental designs? if not, would you be open to consulting and doing what you did here -- suggesting ways to control for key variables? experiments relate to cancer research. contact info in bio. They are called CROs (contract research organizations). Pay them money and they will work on your experiments for you.
- stultissimus 4y ago
  > 1. the parent raised questions in a neutral way. these questions seem essential for validating experimental design. why would peer reviewers present such questions in passive-aggressive ways, and how can we fix this? Peer review is obviously a complex and controversial issue, but some key points (at least in life/medical sciences) include: A. Your reviewers are very often your competition. Reviewers are supposed to be subject matter experts in your area of research, and academic science is a small world. The other subject matter experts are exactly the people competing with you for grants, to finish projects first, for trainees, prizes, etc. (You can typically ask that specific people do/don't review your paper, but it's at the editor's discretion. Some fields are simply too small to take such preferences into account.) You can often identify your (supposedly anonymous) peer reviewers because they respond with a critique that your paper should cite some specific papers, and they are the common name on the bylines of those papers. B. Peer review is uncompensated work by academics, very often done for for-profit publishers. Hard to be thrilled with that paradigm (though some scientists feel it's a reasonable 'academic duty'). C. The mindset in peer review is often more about gatekeeping the journal hierarchy than about simply ensuring good experimental design. Publishing in top journals is often a career-making achievement. It is incredibly common for reviewers to ask for (often very time consuming) additional experiments based on their opinions about what is interesting, what a paper in the journal should look like, etc. There is a bias where reviewers don't want someone else to have an easier time publishing in X journal than they did. D. Not exactly a critique of peer review, but I think it's important to realize that peer review is not even intended to address one of the major problems in science – irreproducible results and/or scientific fraud. Reviewers have to take all data presented on face value. At best, peer review is simply a check against poor experimental design, errors in reasoning, and authors making claims stronger than what the data supports. > 2. could you kindly recommend services/consultancies to validate experimental designs? if not, would you be open to consulting and doing what you did here -- suggesting ways to control for key variables? experiments relate to cancer research. contact info in bio. As mentioned, CROs are the companies in this space, though I'm not familiar with any that focus specifically on vetting experimental design.
hanniabu 4y ago
> An important question will be whether viruses, which evolve far faster than eukaryotes like Halderia (let alone than humans), can turn the tides in the evolutionary arms race and become the exploiters of the Halderia. I'd assume that's the case, otherwise I feel like there would be more Halderia and/or less viruses
bee_rider 4y ago
Is “evolving faster” more like 3x-10x, or more like 100x-1000x… I guess what I’m wondering is, can we help the Halderia out somehow so it can keep pace, or is it just operating on a total different timescale than a virus.
- stultissimus 4y ago
  Mutation rate ranges many orders of magnitude. See a figure here (linking a tweet (not mine) to avoid journal paywall, but underlying paper is linked in the tweet): https://twitter.com/DrCJ_Houldcroft/status/1527243868739076096?s=20 https://twitter.com/DrCJ_Houldcroft/status/15272438687390760... Halderia would be 'lower eukaryotes'; we are 'higher eukaryotes'. The idea of 'helping the halderia out' by increasing mutation rate is kind of funny; that would almost certainly kill them (this is largely how radiation kills us). You would need to be able to reliably and specifically introduce favorable mutations (i.e. those that increase fitness), which is far beyond current capabilities.
  - bee_rider 4y ago
    Haha, ok. I was thinking by a totally inappropriate analogy — I mean, we “helped” dogs evolve in a direction that lets them work for us better, including things like defending our livestock from wolves and coyotes. But coyotes don’t evolve many orders of magnitude faster than dogs!
    - kuhewa 4y ago
      It isn't just mutation rate but generation time as well, even with the same mutation rate a virus that replicates several times a day would evolve faster. But there's certainly scope for us to artificially select for traits in virovorous organisms for our own purposes, we commonly do for crop plants to provide viral resistance or tolerance and viruses don't overcome them too quickly. Traditional methods have included x-ray mutagenesis where we crudely induce mutations in a lot of plants and see if any are useful afterward.
  - dogma1138 4y ago
manyteee5 4y ago
Anthromorphize means to attribute human characteristics to something not human. Surely you're not saying that "trying" is a uniquely human behavior?
- OJFord 4y ago
  Is there a similar word that means characteristic of kingdom animalia? I think the usage was clear and fair enough.
- effingwewt 4y ago
  *anthropomorphize.
OJFord 4y ago
3 - or simpler, look at the ratio of virus to non-virus that's 'consumed'? As a human I accidentally ingest a lot of 'bad bacteria', it's just dwarfed by the nutritious (or delicious..!) stuff. I think that's what GP's getting at - distinguishing 'accidental'/sife-effect consumption from intentional; not necessarily that it's great sentient or evolutionarily designed intent.
calvinmorrison 4y ago
Viruses - like mosquitos.. can anyone pontificate the downside to wiping viruses out
- acyou 4y ago
  Here's some pontificating: Viruses form a part of a control system for themselves and for higher and larger life forms. If any system becomes unstable, or if one organism starts dominating or growing out of control, the other organisms have an evolutionarily created self interest in bringing things back into balance. Viruses play a huge part in this self regulation mechanism. Eliminating viruses would have the unfortunate effect of decreasing overall system stability for biological systems at every level.
  - paulstovell 4y ago
    Fascinating!
- throwaway81523 4y ago
  Viruses like other microbes are important to the biology of larger organisms. E.g. https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000028 https://journals.plos.org/plosbiology/article?id=10.1371/jou...
deleted 4y ago
[deleted]
p-e-w 4y ago
> these are the kind of points peer reviewers would raise (though typically in far more esoteric and passive aggressive ways...) If you don't mind me asking, how do you deal with this kind of culture, where a normal process is being purposefully obstructed with such behavior from the reviewer? Do you ever call people out who sprinkle their "reviews" with such passive aggression? What is their defense? What highlights does your profession have that make it worth putting up with this?
- icelancer 4y ago
  I have an i10 index of 2, h index of 3, 71 total citations. Not that impressive, but just goes to show I have some experience in this area. So... > If you don't mind me asking, how do you deal with this kind of culture, where a normal process is being purposefully obstructed with such behavior from the reviewer? You just come to expect it. I realize this isn't the best answer or even a reasonable one, but it's how it is and there's really no controlling it. > Do you ever call people out who sprinkle their "reviews" with such passive aggression? No. Your field is dominated by experts who have a clique and run a crony network of influencers; getting mad at one of them is a great way to ensure you never hit tenure track / get punished on papers in the future (many journals are not blinded, or even if they are, it's fairly obvious who wrote a blinded paper given the subject matter in a niche field and/or timing attacks on the paper's submission + researcher's social media posts on the topics). Sometimes - most of the time in my field - you have no idea who the reviewers were. I think this is typical for most science fields. > What is their defense? They suffered by much worse hands; really, they're being nice. (That's what they tell themselves.) > What highlights does your profession have that make it worth putting up with this? Very few. I work for a for-profit company, so the research we publish helps bolster the company's image, can be used in marketing, and so forth. Going from zero to one feels amazing. One day you're a guy with a dream that you'll publish an influential paper someday and give back to science, the next you have that publication credit - maybe even lead author credit - and going from 1 to N is just nowhere as interesting as going 0 to 1... like most things in life. For some of us, science is in our blood, and it's our calling. Whether we like it or not. Most of the time, we don't. But we do it anyway.
  - 4y ago
mgsouth 4y ago
Virus sinks: did you see the recent paper published in Journal of Allergy and Clinical Immunology? [1] It cites lots of other studies showing that nasal epithelial cells create extracellular vesicles (blobs of stuff floating outside the cells) that have receptors for cold viri. Since the vesicles don't have DNA the virus can't replicate. Infected vesicles get swept up the rest of the immune system, so they're decoy Roach Motels for viruses. The study shows that when the nose gets colder fewer vesicles are created, and claims that's why cold and flu cases increase in the winter. [1] https://www.jacionline.org/article/S0091-6749(22)01423-3/fulltext https://www.jacionline.org/article/S0091-6749(22)01423-3/ful...

panabee 4y ago

great answers to great questions. 1. the parent raised questions in a neutral way. these questions seem essential for validating experimental design. why would peer reviewers present such questions in passive-aggressive ways, and how can we fix this? 2. could you kindly recommend services/consultancies to validate experimental designs? if not, would you be open to consulting and doing what you did here -- suggesting ways to control for key variables? experiments relate to cancer research. contact info in bio.

KRAKRISMOTT 4y ago
> 2. could you kindly recommend services/consultancies to validate experimental designs? if not, would you be open to consulting and doing what you did here -- suggesting ways to control for key variables? experiments relate to cancer research. contact info in bio. They are called CROs (contract research organizations). Pay them money and they will work on your experiments for you.
stultissimus 4y ago
> 1. the parent raised questions in a neutral way. these questions seem essential for validating experimental design. why would peer reviewers present such questions in passive-aggressive ways, and how can we fix this? Peer review is obviously a complex and controversial issue, but some key points (at least in life/medical sciences) include: A. Your reviewers are very often your competition. Reviewers are supposed to be subject matter experts in your area of research, and academic science is a small world. The other subject matter experts are exactly the people competing with you for grants, to finish projects first, for trainees, prizes, etc. (You can typically ask that specific people do/don't review your paper, but it's at the editor's discretion. Some fields are simply too small to take such preferences into account.) You can often identify your (supposedly anonymous) peer reviewers because they respond with a critique that your paper should cite some specific papers, and they are the common name on the bylines of those papers. B. Peer review is uncompensated work by academics, very often done for for-profit publishers. Hard to be thrilled with that paradigm (though some scientists feel it's a reasonable 'academic duty'). C. The mindset in peer review is often more about gatekeeping the journal hierarchy than about simply ensuring good experimental design. Publishing in top journals is often a career-making achievement. It is incredibly common for reviewers to ask for (often very time consuming) additional experiments based on their opinions about what is interesting, what a paper in the journal should look like, etc. There is a bias where reviewers don't want someone else to have an easier time publishing in X journal than they did. D. Not exactly a critique of peer review, but I think it's important to realize that peer review is not even intended to address one of the major problems in science – irreproducible results and/or scientific fraud. Reviewers have to take all data presented on face value. At best, peer review is simply a check against poor experimental design, errors in reasoning, and authors making claims stronger than what the data supports. > 2. could you kindly recommend services/consultancies to validate experimental designs? if not, would you be open to consulting and doing what you did here -- suggesting ways to control for key variables? experiments relate to cancer research. contact info in bio. As mentioned, CROs are the companies in this space, though I'm not familiar with any that focus specifically on vetting experimental design.

hanniabu 4y ago

> An important question will be whether viruses, which evolve far faster than eukaryotes like Halderia (let alone than humans), can turn the tides in the evolutionary arms race and become the exploiters of the Halderia. I'd assume that's the case, otherwise I feel like there would be more Halderia and/or less viruses

bee_rider 4y ago

Is “evolving faster” more like 3x-10x, or more like 100x-1000x… I guess what I’m wondering is, can we help the Halderia out somehow so it can keep pace, or is it just operating on a total different timescale than a virus.

stultissimus 4y ago
Mutation rate ranges many orders of magnitude. See a figure here (linking a tweet (not mine) to avoid journal paywall, but underlying paper is linked in the tweet): https://twitter.com/DrCJ_Houldcroft/status/1527243868739076096?s=20 https://twitter.com/DrCJ_Houldcroft/status/15272438687390760... Halderia would be 'lower eukaryotes'; we are 'higher eukaryotes'. The idea of 'helping the halderia out' by increasing mutation rate is kind of funny; that would almost certainly kill them (this is largely how radiation kills us). You would need to be able to reliably and specifically introduce favorable mutations (i.e. those that increase fitness), which is far beyond current capabilities.
- bee_rider 4y ago
  Haha, ok. I was thinking by a totally inappropriate analogy — I mean, we “helped” dogs evolve in a direction that lets them work for us better, including things like defending our livestock from wolves and coyotes. But coyotes don’t evolve many orders of magnitude faster than dogs!
  - kuhewa 4y ago
    It isn't just mutation rate but generation time as well, even with the same mutation rate a virus that replicates several times a day would evolve faster. But there's certainly scope for us to artificially select for traits in virovorous organisms for our own purposes, we commonly do for crop plants to provide viral resistance or tolerance and viruses don't overcome them too quickly. Traditional methods have included x-ray mutagenesis where we crudely induce mutations in a lot of plants and see if any are useful afterward.
- dogma1138 4y ago

manyteee5 4y ago

Anthromorphize means to attribute human characteristics to something not human. Surely you're not saying that "trying" is a uniquely human behavior?

OJFord 4y ago
Is there a similar word that means characteristic of kingdom animalia? I think the usage was clear and fair enough.
effingwewt 4y ago
*anthropomorphize.

OJFord 4y ago

3 - or simpler, look at the ratio of virus to non-virus that's 'consumed'? As a human I accidentally ingest a lot of 'bad bacteria', it's just dwarfed by the nutritious (or delicious..!) stuff. I think that's what GP's getting at - distinguishing 'accidental'/sife-effect consumption from intentional; not necessarily that it's great sentient or evolutionarily designed intent.

calvinmorrison 4y ago

Viruses - like mosquitos.. can anyone pontificate the downside to wiping viruses out

acyou 4y ago
Here's some pontificating: Viruses form a part of a control system for themselves and for higher and larger life forms. If any system becomes unstable, or if one organism starts dominating or growing out of control, the other organisms have an evolutionarily created self interest in bringing things back into balance. Viruses play a huge part in this self regulation mechanism. Eliminating viruses would have the unfortunate effect of decreasing overall system stability for biological systems at every level.
- paulstovell 4y ago
  Fascinating!
throwaway81523 4y ago
Viruses like other microbes are important to the biology of larger organisms. E.g. https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000028 https://journals.plos.org/plosbiology/article?id=10.1371/jou...

deleted 4y ago

[deleted]

p-e-w 4y ago

> these are the kind of points peer reviewers would raise (though typically in far more esoteric and passive aggressive ways...) If you don't mind me asking, how do you deal with this kind of culture, where a normal process is being purposefully obstructed with such behavior from the reviewer? Do you ever call people out who sprinkle their "reviews" with such passive aggression? What is their defense? What highlights does your profession have that make it worth putting up with this?

icelancer 4y ago
I have an i10 index of 2, h index of 3, 71 total citations. Not that impressive, but just goes to show I have some experience in this area. So... > If you don't mind me asking, how do you deal with this kind of culture, where a normal process is being purposefully obstructed with such behavior from the reviewer? You just come to expect it. I realize this isn't the best answer or even a reasonable one, but it's how it is and there's really no controlling it. > Do you ever call people out who sprinkle their "reviews" with such passive aggression? No. Your field is dominated by experts who have a clique and run a crony network of influencers; getting mad at one of them is a great way to ensure you never hit tenure track / get punished on papers in the future (many journals are not blinded, or even if they are, it's fairly obvious who wrote a blinded paper given the subject matter in a niche field and/or timing attacks on the paper's submission + researcher's social media posts on the topics). Sometimes - most of the time in my field - you have no idea who the reviewers were. I think this is typical for most science fields. > What is their defense? They suffered by much worse hands; really, they're being nice. (That's what they tell themselves.) > What highlights does your profession have that make it worth putting up with this? Very few. I work for a for-profit company, so the research we publish helps bolster the company's image, can be used in marketing, and so forth. Going from zero to one feels amazing. One day you're a guy with a dream that you'll publish an influential paper someday and give back to science, the next you have that publication credit - maybe even lead author credit - and going from 1 to N is just nowhere as interesting as going 0 to 1... like most things in life. For some of us, science is in our blood, and it's our calling. Whether we like it or not. Most of the time, we don't. But we do it anyway.
- 4y ago

mgsouth 4y ago

Virus sinks: did you see the recent paper published in Journal of Allergy and Clinical Immunology? [1] It cites lots of other studies showing that nasal epithelial cells create extracellular vesicles (blobs of stuff floating outside the cells) that have receptors for cold viri. Since the vesicles don't have DNA the virus can't replicate. Infected vesicles get swept up the rest of the immune system, so they're decoy Roach Motels for viruses. The study shows that when the nose gets colder fewer vesicles are created, and claims that's why cold and flu cases increase in the winter. [1] https://www.jacionline.org/article/S0091-6749(22)01423-3/fulltext https://www.jacionline.org/article/S0091-6749(22)01423-3/ful...