Katy-Jane writes:

Hi all,

I recently came across TWiN after getting caught up with TWiP and TWiV, and I thought I’d write in to let you know how much I enjoy it! 

My knowledge of neuroscience is very basic. I teach a couple of lectures on the nervous system in freshman/sophomore level anatomy & physiology classes. Additionally, my mum suffered a severe stroke 4 years ago. She has made a remarkable recovery and if you did not know her previously, you would not be able to tell, other than she now suffers from aphasia. It has led to some interesting communication mishaps, and all of us have had to hone our artistic “skills!”

I love the dynamics between the various TWiN hosts, and with you guys I really feel like I am sitting at a bar just enjoying a conversation. I will admit that some of the material is over my head, but what I really enjoy is the critical evaluation of the papers. You sometimes comment that you are being “reviewer 3,” but I actually find that part interesting. I am not the best at critically evaluating scientific research, so hopefully by hearing you guys’ thoughts on it, I will learn better what to look for. 

Thanks again for yet another great podcast.

Katy-Jane Shanak

Adjunct Faculty in Veterinary & Dairy Sciences

Northcentral Technical College

Wausau, WI

Brenda writes:

Hello Vincent, 

Looked back in my e-mails to figure out when I started watching TWIV and the earliest reference I can find is mid-May last year. 

Now microbe.tv in its various podcasts on science topics is my station of choice.   I just watched my first TWIN (20).  I plan to go back and watch from number 1.

I do see that you mostly manage to have female representation in most podcasts – which I suspect is no mean feat, given the likelihood that they are rather in the minority in the world of neurologists.  I would be interested to know if there are any statistics about that.

I thought I would send you this as a possible lead into a podcast on how it impacts what neurologists study, how it is reported and so on.  I have not read the full article as it requires subscription and anyway, Microbe.TV will be first on my list for £s, as I value the non-specialist angles that Rich Condit so ably supplies for TWIV. 

https://www.newscientist.com/article/2283801-neuroscientists-are-ignoring-the-differences-between-males-and-females/

Neuroscientists are ignoring the differences between males and females | New Scientist

Top neuroscience research papers are eight times more likely to only study male participants or samples compared with female-only studies, a review has found. In addition, only 4 per cent of …

www.newscientist.com

One point in Podcast 20 did catch my attention.  As a female I would like to point out that a permanent unpleasant odour is not a feature of female toilets. I suspect that this is related to the absence of urinals. I would suggest that perhaps research into the design of this piece of plumbing might reduce the problem somewhat.  That is not to say that there is no problem with odours in female toilets – colognes, perfumes and hairsprays being the main culprits in my experience – but they are generally short lived. 

Thank you again for all your podcasts. 

Brenda

Black Isle Scotland

Ingrid writes:

Dear TWiNers,

Aside from the question of how it works, I naively wonder if maybe the reason for the constant re- ‘mapping’ of olfactory and maybe other sensory input (other than visual) you discussed in the recent TWiN (#20 – Drifting Aromas) has to do with preventing a sort of ‘wearing out’ of the original neural locations through constantly pressing on the same “keys” in a way?

Could this popular science article I came across have any bearing on this?

https://www.quantamagazine.org/the-brain-rotates-memories-to-save-them-from-new-sensations-20210415/

It talks about olfactory memories being temporarily stored in the sensory receptor area of the brain itself (rather than immediately going into either “short or long-term memory storage” areas of the brain), but somehow in a ‘rotated’ manner – the analogy was to rotating a piece of writing by 90 degrees in order to write something different onto the same piece of paper – so as to not overlap and confuse a current sensation with the stored memory of that sensation (best as I can interpret though not quite understand the point of the paper!).

At first hearing, I disagreed with Jason about olfactory memories like ‘banana’ being so obviously inherently less likely to ‘drift’ compared to other memories (even though I do have some very strong smell-linked-to-emotional memories from my childhood that are stronger emotionally than the drier factual-seeming memory of the same event that I also have – but which might be a memory-of-a-memory, or even a constructed, false ‘memory’ from being told of the event over the years). 

If a subject didn’t smell a banana again after the first time for many years, maybe!

But otherwise, every time you smell a banana after the first time couldn’t your brain be CORRECTING any drift that has happened to the first olfactory memory?

In actual fact, the taste and probably smell of bananas changed for all Americans sometime in the late 60s when the previous commercial monoculture variety (called Big Mike) died off from disease and was replaced by a new and different-tasting variety (Cavendish – it’s a monoculture too, so very susceptible to the same fate as Big Mike). That’s apparently why artificially-flavored banana candies etc today taste so different from the real thing – aside from being cloying and artificial, the artificial flavor hasn’t been recalibrated from the Big Mike flavor. I never realized this until reading about it in recent years, but AFTER reading about it (hmm!) it seems to me that I do recall a different banana flavor from my childhood, ‘yellower’ and less bland than today’s bananas.  (As a side issue, I’ve been on a many-years-long quest to find my mother’s old bananabread recipe from the back of the graham flour box that was so much better than ANY bananabread I’ve had since, so sadly, aside from the missing flour-to-graham flour ratio, it might be the actual banana that made the difference.)

Since even with relatively few olfactory receptors (compared to other animals) we can distinguish so many different shades of smell in wines, rose varieties, bananas, etc I imagine most things we think of as one discrete ‘smell’ like ‘banana’ probably comprise many different chemical odors in one soup of odors. Re that car-to-truck shift that Vivianne alluded to – it must also happen with smells, so the shift in identified smell from “banana” to “pineapple” for example is probably a continuum, without an obvious jump from one to another.

Question: I have been searching and searching for a popular science article I thought I recently read about how olfactory (receptors? signals? neurons?) have now been found to be ubiquitous throughout the brain or nervous system aside from smell and pheromone reception areas and may indicate a previously unknown and important signalling method in the brain. Am I crazy? Did I construct this memory? If you happen to know better than I do what I am babbling about I would appreciate any link or reference, I just told a friend I would send her a link to this article that now I can’t find anywhere. Also of course wondering if it would have any relevance to your recent TWiN.

For me, listening to TWiN is like trying to follow a deep discussion in a language I only have a rudimentary understanding of, like Swedish or French. I come away with an excited feeling of maybe having learned something, but on the other hand I can’t usually describe it to someone else so the ‘learning’ is probably an illusion! However I really enjoy listening to you scientists working on interpreting new data and trying to make sense out of it, that’s probably what is actually exciting, just listening in on the process of scientific discovery about the universe around and inside us.

Thanks for that and everything else you do,

–Ingrid

Berkeley CA – perfect weather here, and somehow for once NOT the bottom of the funnel for of all of CA’s smoke. (Sorry, Jason, I wish you didn’t have to be receiving it either!)

Dave writes;

Good day Twinnowers of neuroscientific knowledge,

In Twin 012 Ori said “adeno-associated viruses that over express these genes or RNAi constructs to reduce the expression of these genes.”

Is this kind of procedure where a specific gene is introduced into cells using viral vectors doable in the same sense as

“Yeah, we can build a channel tunnel”

or as

“Yeah, we can fly a plane from here to Paris”

or perhaps as

“Yeah, I can call my friend in Paris on the phone”?

How much time, and perhaps money, would it take to create a viral vector that introduces RNAi for a segment after one had the nucleic acid sequence in question.  I expect that large segments will be more costly than shorter ones.  Also, some viruses will infect certain types of cells more than others, which would be good if they were infecting the cells under study, and bad if they were preferentially infecting cells that were not.

So what is the current context?  Do you guys do this, or would you have to contract out?

Dr. Dave Jackson

Dave writes:

Good day Vectors of TWINfestation, 

I have a polio question, which I hope is appropriate for Neuroscience.  You guys have the shortest email list in the TWIXiverse, so I have some hope of hearing the answer while I still remember why I asked the question. 

As I understand the history, polio was originally thought to be a respiratory infection due to an unfortunate choice of animal model.  Even after the mode of transmission was correctly identified, only non-pharmacological interventions were available. 

For decades, communities had to adopt policies to reduce the spread.  I believe hand-washing was encouraged with public education programs aimed both at school children and adults.  Presumably, there were other interventions that, in retrospect, were not as effective.  I believe many public swimming pools were closed.  Some communities did not allow non-residents to enter.  My point is that there were decades of public education programs, some more influential than others, and behavioral interventions, some more effective than others.  Can our experience with polio inform our decisions regarding interventions and public education with respect to Covid, which, like polio, we did not understand and could not explain its pathogenesis? 

Thank you for all that you do, 

Dr. Dave Jackson

Margie writes:

Greetings TWiN friends!

I am so excited to have a real reason to email you! (I have been trying to come up with an excuse since TWiN 10 when you didn’t have any letters & requested emails. — Come to think, do I get bonus points for non-Covid19 questions??? LOL.)

Background: I have multiple sclerosis (so a bit of familiarity with neuro-degeneration). I was an elementary school teacher & then an elementary school librarian. I am now medically retired.

Fair warning in advance— I am very good at unintentionally making short stories long. So apologies for the length!

Today (Wednesday 10/28/20), there was a report shared that caused quite a hopeful stir in my MS Gym FB group. 

Here’s the link shared for the report made on a local TV news show. I’ll also add screenshots of the transcript. 

(https://wgntv.com/news/medical-watch/breakthrough-research-shows-hope-for-reversing-damage-in-neurological-disease/?fbclid=IwAR1fB7FrnfP9esWcrzQOpOO68_RnViUUHpltCBzmCaUTUxsQNmFjrclIuSg)

Obviously, that report could be sensationalized, so I searched for the more specifics. 

It turns out that the news stir is caused because of a new publication from 26 Oct 2020 in Nature Immunology titled “A new neutrophil subset promotes CNS neuron survival and axon regeneration. “

Link to article: https://www.nature.com/articles/s41590-020-00813-0 

I’d like to suggest this as an article for you guys to discuss— especially as I have not yet found a way to read more than the summary. (Quite possibly I won’t understand it much without a lot of thinking & study, so not being able to access the whole paper might be a moot point anyway… which would make listening to you guys discuss it that much more useful & valuable to me!) (Ahem. Hint hint! 😃)

First question:

From what I read in the “Extended data” their in vivo experiments looked at the optic nerve. 

In TWiN 8 you guys discussed “Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice”

(https://www.sciencedirect.com/science/article/abs/pii/S0092867420302865?dgcid=rss_sd_all) — Which also looked at eye related neurons/cells. (Apologies for the simplification here & in future.)

The two papers look at different things (a protein vs white blood cell), but they seem parallel? 

Both seem to be looking at regeneration in nerve cells — but I can’t really tell if they’re looking at the same things or just similar things. Can you guys expound/explain it to me?

Also, both are looking at eye-related nerves. Is this because it’s easier/doable/simpler to get to & study optic nerves? 

Now let’s move on to questions where it will be even more apparent that my science is elementary school level. 

Third question:

Apparently, the Sas et all group also did experiments in vitro using human cell lines. 

Since I can’t read the paper, I can’t tell the order.  

Is it usual to first experiment in cells in vitro then move to animal studies? 

They talk about next steps. Obviously this would be different depending on what you’re actually studying …  but would you progress to a different animal or to a different type of cells?

(Just FYI here’s a website publication that talks a bit about the in vitro stuff.  https://www.eurekalert.org/pub_releases/2020-10/m-don101920.php )

Fifth question:

About authorship. 

From article website-

“Contributions

A.R.S., K.S.C., A.D.J., C.Y. and A.L.K. performed experiments and data analysis. R.M. oversaw RNA-seq analysis. B.M.S. wrote the manuscript and coedited it with the help of the other authors. B.M.S., R.J.G. and A.R.S. directed the studies.”

In school librarian world, the person who does the writing is the author. 

But the person who wrote the manuscript isn’t the first author listed. 

I’m guessing maybe the principle investigators are listed first in the author list?

How do they decide who gets to be “first author” anyway? And why is that so important? (I hear it emphasized often in the different microbeTV podcasts.) Is it something to do with the “publish or perish” part of university professorship?

Sixth question:

This is about peer review & publication. 

The article website lists dates for submission, acceptance, & publication. 

Obviously the time gap between submission & acceptance is the time when peer review is done. 

I was able to read the peer review comments. At the end there’s a place for “Author Rebuttal to Initial comments” but it is blank. 

The journal’s letter to the manuscript authors does say:

“We invite you to revise your manuscript. 

“* Include a “Response to referees” document detailing, point-by-point, how you addressed each referee comment. If no action was taken to address a point, you must provide a compelling argument. This response will be sent back to the referees along with the revised manuscript.”

I can’t see the actual article to read their response to referees. 

I wondering:

  • Is this a usual request?
  • What if you don’t have funds to do the experiments the referees request?
  • What if you just don’t want to do them?
  • Do journals refuse to publish manuscripts if the authors won’t address the referees questions? Can the authors get away with justifications of why they don’t do the referees requests? (I’m assuming comment about “Do not hesitate to contact us if there are specific requests from the reviewers that you believe are technically impossible or unlikely to yield a meaningful outcome” might be two of the reasons authors try to use to not do the requests?)
  • Are the referees requests usually things that really need to be done or often things designed to delay or impede competitors?

I really don’t have much knowledge (much less understanding) of the peer review process. If you could point me to someplace to learn about it, I’d be obliged. 

Last question:

There seems to be a lot of hype generated by the University of Ohio — where the authors work — about the discovery & its potential. 

Cynical me wonders if generating hype is about creating reputation to encourage funding. 

But perhaps this really is a big discovery?

It seems to me, however, that there’s a lot of steps & research that have to happen before it might actually be something that could have an impact on my life. 

Don’t get me wrong. I’d be absolutely delighted for my CNS to heal its damage. But even if this discovery proves to be pivotal…. it can’t be applied to my brain any time soon!

So what do you guys think? Big deal or not? Worth the hype? Or important & encouraging but not more so than other advances. (Like the papers discussed in TWiN 8)

Thanks very much for the podcasts. 

Yes, they are always over my head. Or at least completely out of my experience. I do enjoy getting glimpses into a world so different from my own.  (Meaning the world where you know & study how the brain – or other science works – vs the world where you study how to get kids to read for pleasure or do their homework!)

Thanks again. And keep on TWiN-ning!

😃,

Margie

P. S. 

I did consider sending this email to Immune – but I thought the emphasis on nerves & the similarity to the article in TWiN 8 made this the more appropriate choice. If not, please feel free to use the email there.