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TWiM 87 Letters

Varun writes:

Greetings TWiM Profz,

As a person constantly associated with Clinical microbiology, I have seen the resistance grow up one by one. I couldn't agree more about the problem of using carbapenems, owing to MBL. In my personal experience, carbapenems have become almost "of no use". In last couple of months I have also begun seeing resistance to some last resorts, inc Tigecycline. And a couple of days ago, I have also seen a clear case of Colistin resistance. Tigecycline and colistin resistance is now well documented in literature, hence I'm not surprised. Your thoughts?

Clearly we are desperately in need of new battle options. One of the papers that I happened to have read recently in connection is Collateral sensitivity. I believe it is a TWiM able topic, at least a worthy discussion.

Use of Collateral Sensitivity Networks to Design Drug Cycling Protocols That Avoid Resistance Development. http://stm.sciencemag.org/content/5/204/204ra132.abstract

Thanks for everything that you do
TWiX Fan,

Varun C N

Dave writes:

Hi y'all! Haven't flirted with 40° recently, but San Joaquin Valley real humidity is higher than theoretical due to decorative and crop tree respiration, I think, despite severe drought. Air quality the worst, and better than it used to be. Ground level ozone cooks right up on still, sunny days, not to mention particulates with a breeze. So much for pleasantries I previously skipped.

Email writer on episode of Aug. 14 called attention to scrubs in hospitals, and cross contamination. My limited experience leads me to think those thoughts delightful, and heartily endorse it. Also, if a big place, imagine some of the hues!

Mostly moved to propose hypothesis re: the increase of scrubs worn promiscuously between hospital areas, but also in and out and home. Lack of locker rooms and time were mentioned, and deserve mention. Also, however, I believe many workers who are not surgeons have to buy and launder their own these days (the old binsfull tend to walk off, one by one, adding to facility cost). Why mess up street clothes, then?
Eh! I digressed from hypothesis. In current social environment, a certain pride in glorious, elevated status role in medical facility impels some of these garment decisions. I'm specially important, it hints, and busier than you. It extends easily to lab techs and nursing assistants. When observed in MDs specifically, however, it grabs the identity more simply than the longer white lab coat, and becomes a source of silent pride. This is concomitant with decline of physician/surgeon's role as social dignitary and repository of wisdom. Rather, dignity having been generally deflated (thank gawd) in recent culture, physicians/surgeons have become tradesmen. They also are finally no longer humiliated by mere lowly student status. They also really do have special skills and earnings to signify.

They are thus deflated by their own identity search, at base. They have abandoned role of interested, knowledgeable advisor, and slipped into that of mechanic or technologist of uncertain trustworthiness. This sociological trend has been proceeding for several decades.

Scrubs of identifiable hues, anyway, are a brilliant suggestion. So are locker rooms, and time in to-the-minute productivity demands to ceremonialize their use. They seem like a consciousness-raising device as well. Bottom line, the casual cross contamination is reminiscent of 19th century practice. It deserves attention.
Sorry. I shouldn't listen in middle of night, and submit to urge to share by writing.

All the best,
Dave


John writes:
Dear amphitropical podcasters,

In TWiM 84 Melanie Thomson said she needing to come up with an allergy test for maggots before letting them eat people. Do the FDA and IRBs impose similar requirements in America? Does approval of maggots for use in America make it easier to get approval in other countries?

John

P.S. I have attached a photo of three _Lucilia sericata_, the fly licensed for use in the USA, eating a dead slug.

[vr: maggot therapy http://en.wikipedia.org/wiki/Maggot_therapy]

Michael writes:

Hello All,

Thank you for all you do, I love to listen to all your podcasts as I am at the bench, I am a Medical Laboratory Scientist (new terminology for Medical Technologist).

In TWiM 85, when Michael described the Modified Hodge Test (MHT) near 53:30, he made two mistakes.

1) It was described that the lawn was of an E. coli that was resistant to carbapenems. That is not correct, it is actually sensitive to the carbapemens, and we do a streak of QC orgs and clinical isolates from the carbapenem disk (Meropenem or Ertapenem) out to the edge of the plate. If the isolate has certain carbapemenases, it does diffuse like Michael said, and allows the E. coli to grow closer to the disk.

2) Michael stated in essence that the MHT will detect MBLs. That is not correct. It detects KPC type carbapemases well in Enterobacteriaceae, but according to CLSI (Clinical Laboratory Standards Institute), it is only 11% sensitive for the New-Delhi metallo-β-lactamase.

I also attached a recent paper from JCM on a possible way to detect carbapemases using LC-MS/MS in about 75 minutes.

Please keep up all the good work, I just finished my first Master’s course, heading towards a degree in biotechnology, I decided to continue on with school largely because of your podcasts (I started listening to TWiV in 2009), but only part time because I believe there is a lot to learn in a clinical micro lab.

Michael, MLS (ASCP)CM
http://jcm.asm.org/content/52/7/2500

 

 

TWiM 86 Letters

 

Suzanne writes (re Aphids):

The best way to get rid of aphids in the garden (the ants in my yard love to herd them onto my okra) is a sharp stream of water from the hose. Aphids wash right off! They don't tend to come back right away, either.

John writes:

While discussing the Siberian doomsday virus (TWiM 74 at 50:00) Michael wonders how the virus survived cosmic rays.

The only charged cosmic ray particles that can penetrate 30 meters of rock or ice are muons. Protons and electrons are absorbed.

I estimate half of muons get through, resulting in a dose of about 1 mSv per year.

Over 30,000 years the virus accumulates a dose around 30 Sv.

It takes 1,000 Sv or more to inactivate a virus. This value is similar for RNA, small DNA, and large DNA viruses. See reference below. So 30 Sv should just make the virus angry and ready to go on a rampage. Or maybe I'm thinking of the Incredible Hulk.

Radiation is even less effective on viruses in ice. The virus irradiation paper says so, and I had independently predicted the effect because most DNA damage is caused indirectly by hydroxyl radicals, which are less mobile in ice.

I look forward to papers about 300,000 year old viruses.

John

References:

Particle Data Group review of cosmic ray propagation:
http://pdg.lbl.gov/2011/reviews/rpp2011-rev-cosmic-rays.pdf

A 1971 paper titled "Inactivation of Thirty Viruses by Gamma Radiation" gives a dose threshold around .4 Mrad, which is similar to 4,000 Sv (gamma rays and muons both convert 1 rad = 1 rem = .01 Sv).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC377377/

I can only say WOW…

Geoffrey writes:

Doctors:

What a funny coincidence. I heard a letter of mine read in episode 78 then, two letters later, you read Matt's letter. The coincidence is that I asked almost exactly Matt's question to my allergist not 2 months before you read it on your podcast. My doctor didn't think that nasal mucosal colonization was a "thing" so a transplant was unlikely to have any real effect. I don't think that he noticed my vulcan-like raised eyebrow at that answer and we went on with the visit. I will be sending him a link to the letter and the episode of the podcast. If he decides to test an off-label use of mucosal biota on me, then I'll try to let you know how it works. Thanks for reading "both" my letters and thanks for the encouragement.

Don writes:

While reading "small things considered" it was mentioned that chloroform was used to sterilize the soil in an experiment on exoenzymes. From behind the "paywall" I was unable to find vapor concentrations, but wondered if this could be used in the treatment of sepsis. Chloroform was used as a general anesthetic, but with some cardiotoxicity. Is there any data on using chloroform to treat sepsis in lab animals? I suppose there would be some concern about massive demise of the bacteria triggering a cytokine storm, like t[he Herzheimer reaction when siphylis was first treated with penicillin.

Your podcasts are wonderful and do so much to foster scientific literacy.

Thanks again

Don Kingsley Jr. MD

Robin writes:

Tuberculosis

Pott's disease is tuberculosis of the spine causing vertebral body collapse and kyphosis.

Kyphosis is "curved", convexity backwards, as in the Hebrew "kefufa" referring to non-terminal forms of the letters
כנפ&צ

Anyone making a decision for respiratory isolation for tuberculosis should have been trained at least once to competence in the performance of a Ziehl-Nielsen stain. While a negative result does not change a clinical decision to commence respiratory isolation, a positive result instantly makes a whopping difference in the clinical picture.

There are things every physician should have learned to do, including a manual CBC in a Wintrobe haemocytometer, a spun haematocrit, a Wright's stain, a silver stallion sigmoidoscopy, a lumbar puncture, endotracheal intubation, etc. These are as basic as learning to ride a bicycle is for most people.

Surprisingly, most hospital labs do not even have the reagents for the Ziehl-Nielsen stain at hand. They should have single-use aliquots of the reagents in a freezer, so that even if the technician cannot do the stain, the physician caring for the patient should do it.

Oxygen dissociates from haemoglobin at various partial pressures. Foetal haemoglobin holds on to oxygen more avidly than in the adult because it has a lot less oxygen around. Deep sea fish haemoglobin is a champion in this regard.

Rebekah writes:

Hello TWiM team,

I am a Medical Laboratory Scientist and I work in Microbiology at a small Hospital in Michigan. I also teach Cilinical/Diagnostic Microbiology at a community college to future Medical Laboratory Technicians (which is the associate degree level of hospital laboratory bench technicians). I am already thinking of ways to incorporate some of your discussions on Microbiology for my students. I will especially recommend episode 52 which can show the students how far they really can take their careers.

I have been listening to TWiM since June 2014 and have just completed episode 66. I have fairly long drive to work and I also am in the habit of listening to books and pod casts while I am working alone on weekends; which is how I have gotten so far.

As I was listening to episode 66’s discussion of C. diff I really had to laugh at how you found the wording “forms to the shape of the container” so funny! That is the exact criteria we use here at the hospital to determine whether or not a stool sample is suitable for C. diff testing. When I got to work I found the episode online and had my coworker listen this part of the discussion. We both thought the TWiM Team would really get a kick out of this too: If there is a stool sample that a tech is unsure whether it is diarrhea or not a stick test is performed. A wooden applicator stick is put it into the stool about ¾ of an inch. The container is tilted 45 degrees. If the applicator stick falls at an angle greater than or equal to 90 degrees than the stool sample is suitable for testing. This is the way it is stated in our procedure manual! It is hard to imagine, but we get a variety of stool samples and sometimes it is hard to determine if testing should be performed, which is why the criteria is defined in this way. I can’t wait to hear you have a good laugh at the expense of our stick test.

Keep up the good work. I love listening to this pod cast. Once I get caught up on TWiM I am going to start TWiP, and then TWiV. I am saving Virology for last because it has the most episodes and it is the subject I know the least about, but I am looking forward to knowing more. Thank you again for all the hard work and effort that goes in the creating these pod casts they are truly a benefit to the scientific community and the general population.

Rebekah MLS (ASCP)CM

Trudy writes:

Dear TWiMmers,

I just ran across this commentary in Nature and thought you might find it of interest since many of your discussions involve the microbiome/microbiota.

http://www.nature.com/news/microbiology-microbiome-science-needs-a-healthy-dose-of-scepticism-1.15730?WT.ec_id=NATURE-20140821

Kind Regards,

Trudy

 

TWiM 85 Letters

Tom writes:

Hi TWIM, TWIV and TWIP Argonauts,

Your three wonderful podcasts are the nutrient media for growing my scientific knowledge. I have been downloading them from ITunes for a couple of years, and although as a mere amateur I sometimes struggle to keep up with the content, I've never listened to a single one that did not teach me something significant that I can understand. The work load to keep up is heavy, but I've never fallen behind more than a few weeks (well, I"m a couple months behind on TWIP). I even listen to them for an hour or so at night before I fall asleep, and the mellifluous guidance of Dr. Racaniello helps me knit up the ravelled sleeve.

This morning while on the treadmill at the gym, I listened to another, very different kind of science podcast: the UK Guardian's This Week In Science, for June 20, 2014:http://www.theguardian.com/science/audio/2014/jun/20/science-weekly-podcast-longitude-prize-2014. It was entirely devoted to a very interesting discussion of the six possible challenges for the 2014 UK Longitude Prize (celebrating 300 years since the original prize for the invention of the chronometer to determine longitude at sea), including one that was based on the rise of worldwide antimicrobial resistance, so familiar to your listeners. The public was asked to vote to select one of the six possible challenges for the 10,000,000 pound sterling prize, and yesterday the result was announced. The voters picked the challenge to create a cheap, accurate, rapid and easy-to-use point of care test kit for bacterial infections.

I was particularly interested in the discussion between the UK's Chief Medical Officer Dame Sally Davies and Dr. Emily Grossman, educator, broadcaster and expert in molecular biology. It seems that finding a cheap, quick and easy way for GP's and other medical practitioners in out of the way places, like desert communities, is needed to enable them to on the site determine whether an illness is viral or bacterial. This would allow them to stop treating with antibiotics, which continuous and increasing use, of course contributes to the resistance problem. I understand there has been some recent progress in developing a better laboratory test for this purpose, but the quick, cheap, easy black box is still elusive.

I thought you might be interested in this, and maybe some of your listeners, too. I should think there may be a potential winner of the prize among them. So far as I know, competition is not limited to UK persons, and I think there is going to be a five year period allowed for entry and submission of a solution. I hadn't been aware of this prize, and it seems a great way to encourage and stimulate discovery and innovation outside of the academic and corporate institutions.

Thank you again for the great work all of you do to make the world a little more scientifically literate.

The weather in Sausalito, just north of the Golden Gate Bridge, at 3:00 p.m. is typical for our summers: Wind from the west, gusting at 20 knots; clear, with fog ready to roll in over the hills behind us; temperature in the seventies Fahrenheit; barometer 29.92; humidity 55%. In one word, spectacular.

Robin writes:

Mentees

"One of the mentees of my former graduate student"
(Tammy Wagner
UNC Wilmington NC)

Mentor - protege.

http://www.thefreedictionary.com/_/dict.aspx?word=protege

Scrubs

A separate distinctive colour should be reserved for surgical scrubs. No entry or exit from restricted areas wearing scrubs should be permitted. Each area requiring scrubs should use a distinctive colour and enforce the same policy. No distinctive coloured scrubs should be permitted in areas that do not require them.

This needs to be enforced through federal regulations. Many horsespittles will be reluctant to annoy their surgeons, the geese that lay so many of the golden eggs for them.

John writes:

Dear pH-balanced hosts:

It was 22 C in the air, but more importantly the pH was 10 under my feet.(*) I was at the shore of Mono Lake wondering why thermophile acidophile extremophiles get all the publicity. See TWiV 195 "They did it in the hot tub", for example.

What sort of microbes live in cool to cold alkaline lakes?

I know algae grows there, because that is the larval diet of the alkali flies that breed in huge numbers. Unfortunately I was too early for peak fly season.

* According to published figures. I didn't measure, and when I last measured pH of a lake I don't recall the equipment going to 10.

vr: https://microbewiki.kenyon.edu/index.php/Alkaline_Lake lists microbes found in such lakes

Jim writes:

I'm biased towards single-topic discussions because they provide hooks, and are easier to file and retrieve from a blog that is now a living encyclopedia book with the amazing and imaginative tile of "Podcast Encyclopedia." I've stuffed a few TWIV, TWIM and TWIP's into titles that pointed at a key topic, then let listeners discover the related material. All of your episodes, including UrbanAg, are astounding non-fiction, with too many hooks to use as a title and because of that I leave them out.... Probably just lazy.

My solution is to suggest single-topic podcasts; easy to say, of course.

Just thought I'd make the pitch for single-mindedness in case anyone wants to suggest another approach.

Also wanted to ask about all the presentations at each ASM conference and how some have better attendance. Does high attendance suggest importance? If so, is there a way to list or get the topics (links, refs) for each? Might be useful notes for a podcast.

9k people. Must be a madhouse. What a challenge for a robotics class: create a group of drones you could disperse for simultaneous attendance at all the presentations you want to cover...

Regards,

Jim
Smithfield, V

PS I just wrote and asked about popularity of talks at the conference, but it looks like you can see that from the live archive, so disregard that... However, none of them can be downloaded, so I wrote the ASM contact and put a vote in for making things downloadable.


Don writes:

Dear TWiMers,

I listened with interest to your discussion of the ASM annual meeting.

As a food microbiologist I feel compelled to point out that an expert panel recommends not-rewashing bagged salad (http://ucce.ucdavis.edu/files/datastore/234-851.pdf). Of course as microbiologists you may be better than the general public about cross-contamination in the kitchen ;)

If you ever want to chat with a food microbiologist on the podcast I'm available. I co-host a microbial food safety podcast here: foodsafetytalk.com.

I also have a strong ASM connection. I've been an editor for Applied and Environmental Microbiology for almost 10 years and I was elected a AAM fellow this year, although I had to leave the annual meeting before the induction ceremony because I'm also the President of the International Association for Food Protection and we had a board meeting that week.

- Don

=====================================
Donald W. Schaffner, Ph.D.
Distinguished Professor and Extension Specialist

Food Science Building, Room 207
Rutgers, The State University of New Jersey
65 Dudley Road
New Brunswick, NJ 08901-8520

 

TWiM 83 Letters

Matt writes:

Hello TWiM team,

It was great seeing some of you at ASM last week in Boston either in passing between sessions or at the live TWiV episode. I have a few questions about the ASM meeting:
What was something that you all took away from ASM that was particularly interesting, inspiring, or changed your views about a topic?

Second, from episode 78 (a bacterium grows in Brooklyn). There was discussion at some point about the hypoxic environment of the hemolymph impacting the growth of the fungus. That raises a question: I thought that the hemolymph was the ‘blood’ equivalent for insects and I presumed it would be oxygen rich. That made me think about oxygen utilization by bacteria in an animal’s blood stream: blood in animals is oxygen rich, but is mostly bound by hemoglobin. Are bacteria that end up going septic able to utilize that oxygen bound by hemoglobin or must they be able to survive in a ‘hypoxic’ state?

I can’t remember talking about this in my bacteriology classes and my notes and a quick search around the web didn’t turn up a clear answer.

As always, it is a pleasure to listen and learn from all of the TWiX podcasts.
Cheers,
Matt Sammons

Washington State University
Washington/Idaho/Utah Regional Program
College of Veterinary Medicine
Class of 2016

John writes:

Dear recently evolved hosts:

It is 28 degrees C in Grand Junction, Colorado.

At episode 75 time 1:18:10 Vincent suggests that icky stuff that came
out of us probably can't hurt us because it was already in us.
Coincidentally, one of my oldest memories is watching a baby trying to
eat the contents of its diaper and asking my father what happened if
you did that. I suggest listening to an interesting podcast called
"This Week In Parasitism" where the hosts describe parasite life
cycles that depend on recycling waste.

I have two comments on episode 74 time 8:00-10:00.

1. I was confused by the discussion of which species have
endosymbionts. I don't think you were using a consistent definition.

Both cows and humans depend on symbiotic gut bacteria. Those bacteria
like their hosts, but remain potentially free living forms. They are
not obligate symbionts. (Is facultative symbiont a proper term?) In
contrast, mitochondria are obligate endosymbionts.

2. Youth as a species is not an excuse for not having symbionts or
other characteristics. Each of us, human, insect, or microbe,
belongs to a billion year old lineage, but not a billion year old
species. Individual insect species are of comparable age to humans as
a species. We could (and almost certainly did) inherit gut bacteria
from our ancestors, the same way extant termite species inherited
their bacteria from extinct ancestors.

I mention termites because coevolution of termites and their symbiotic
bacteria has been studied and parallel phylogenies reconstructed. I
am far away from my book collection but I recall this was explained in
_Evolution of the Insects_ by David Grimaldi and Michael Engel, which
is worth a read in any case.

http://www.amazon.com/Evolution-Insects-Cambridge-Series/dp/0521821495

Jim writes:

Greetings Micro Monarchs:

Here in Vancouver, it is a wonderful spring afternoon; partially cloudy and 16 C.

I know Dr. R is a bit sensitive about sensationalizing science to scare the public but I must respond with a listener pick , based on the horror scenario of TWIM #78's fatal insect fungus sprouting out of human heads.

My pick is the audio play FUNGUS AMOUNG US by Steve Nubie & narrated by the supremely sinister sounding actor, Malcolm McDowell, and available at audible.com

This gem is right on target, mixing a mad scientist with bad science for some good clean fungus.

Still waiting for the first episode of TWIF.

Regards,

Jim

John writes:

Dear microbial incubators,

It is 40 C in Death Valley and I confess to writing from here in an attempt to win the weather report.‎ I am listening to TWiM during a long road trip.‎ Understanding takes some effort but I haven't crashed yet.

Regarding recent discussion of supplementing antibiotics with bacteria: Is it possible to engineer strains of E. coli ‎and other gut bacteria that are resistant to standard antibiotics? Then ones microflora could survive antibiotics. The resistance would have to be a kind that is rare in the wild but that hospitals are accustomed to dealing with. This would reduce the consequences of trading resistance genes with pathogens.

Warmly,
John

 

 

TWiM 82 Letters

Follow-up on TWiM #81:

Dave writes:

Friends, please forgive brevity of pleasantry; sleep is overdue (internet Player FM re-podcast excellent soporific).

Fear presumptuous correction of trivia you already know, but, re: stress and arterial plaques, some points. Stress is not just perceptual/emotive response to psychological irritants like commuting. The popular usage has been misleading us. It is bodily response to stressors including many non-psychological events, including physical exercise. Therefore, sudden BP changes in even "moderate" exercise, at least when not begun with modulated warmup, is a stressor to arteries and their plaques. Regular exercise benefits longevity in many documented ways, but burst of exercise can also rupture (burst) plaque deposits (as well as initiating arterial damage for initiation of plaque site), releasing gruel into circulation and setting off the big trouble as it clogs the smaller vessels. (With bad luck, even well modulated exercise might do it.)
Arterial plaques, Vinnie, unless my ignorance has overtaken me, are distinctly macroscopic. You can definitely see them. Resident bacteria and biofilms are fascinating news to ignorant self, certainly microscopic, and must have distinct role in plaque derived sudden circulatory injuries. The whole topic sounds thrillingly promising.

So maybe Vince doesn't need a driver, and Michelle had better watch out how she exercises. And we should all hope for fortunate expression of our genes. And for magical cold iron transport, or whatever.

PS Re: pre-, proto-, or prokaryotes vis a vis eukaryotes -- awhile back, in a perverse moment, I skimmed an interview with a Bible literal believer who is biology professor (Dept. Chair? !) at Regency or Liberty University (who can keep em straight), arguing for a 6000 y/o earth and denying evolution "dogma", which he illustrated by nonsense about pro-evolution bias being built into modern bio by sly usages of language such as "pro" and "eu". Since "pro" means "before," he said, the bias is a built in acceptance that they came before "true" cells, thus adding years to the story of life and denying the Biblical true age of life, the earth, and everything, including the evolution of species in any meaningful way..

I betcha the pre and proto discussion mentioned by the letter writer has some place in this teapot tempestuousness. I'd guess "protokaryotes" protects against the suggestion that those cells may have temporal precedence, but are merely simpler versions of the fully formed thing. Or something.

On which note, as long as PhD candidates aren't misled about jobs, the more educated the better. Staff scientist is one good idea. So is Forest Ranger. So is RN. So is high school teacher, or teaching college. Etc. Besides, faculty need students.

Admiringly,
Dave
Fresno

Tarwin writes:

As always thanks for the podcasts.

Weather jumping between 20 / 30 (celsius, depending if I'm in San Francisco or Palo Alto).

Very quick idea / question. Do you think there could be a link between hypoferremia (anemia) and defence against bacteria in relation to it being a conserved trait in humans?

Regards,

Tarwin

Rick writes (re:zombie plants):

Interesting that you focused more on the behavior of the zombie more than that of the vampire.

My question is: what is the mechanism providing the awareness that you would assume would be necessary to comprehend the behavior of the creature being influenced or zombificated.

Does the virus have a telescope to see what's going on at our human scale of existence?

Another great show. Thanks.

Alice writes:

An interesting study regarding the development of the microbiome of infants - would be a fascinating discussion, I think, following your discussions of evidence for bacterial species in brain and urine.

http://www.nytimes.com/2014/05/22/health/study-sees-bigger-role-for-placenta-in-newborns-health.html?_r=0

Might be a good pair with the lung data.

http://www.scientificamerican.com/podcast/episode/lung-microbes-keep-mice-breathing-easy/

Geoffrey writes:

Doctors:

I believe that you missed the most important question in this episode. Can the N-formylated peptides that were found to induce pain in some bacterial infections be used in cooking? I smell a whole host of potential patents in the spicy foods marketplace.

Thanks, as always, for the show.

Shane writes:

Hi TWiM hosts,

I have been a long time listener to TWIM, TWIP and TWIV, but have never written to TWIM before.

I really enjoyed your episode Twim #79, in particular the story about using Listeria as an immunotherapy for Cancer. I am not very familiar with Listeria and my knowledge of the immune system is limited to what I have heard on TWIV and Vincent's Coursera course so this story prompted me for clarification on a few points.

1. If you can use the surface antigen from the tumor to stimulate an immune response against the tumors why don't the tumors themselves already stimulate the required immune response. If the immune system isn't responding to the antigen on the tumor why would it respond to the antigen secreted by the listeria, does the antigen have to be in the cytosol of a cell to be detected?

2. If the listeria has a mutated internalin which won't allow it to attach and get into cells, how is it getting into the cytosol to stimulate the immune response or is it just secreting the antigen in the extra-cellular space? Or is it only picked up and eaten by macrophages?

3. If the the listeria is using these Actin rockets to propel itself from cell to cell, how does it get out of the existing cell, does the actin propel it through the membrane to it just breaks through the both the current cell and the destination cells membrane, or does it use the actin to get to the cell membrane and then use the internalin to get out of the cell and get into the next cell?

Thanks for your amazing efforts on the best science podcasts on the internet, keep up the great work.

 

TWiM 81 Letters

Ravi writes:

TWiM & TWiV team,
Keep up the excellent work! I am an electronics engineer who has never studied biological sciences, but now in my 50's, I find your podcasts fascinating. I listen to episodes while working out - a good combination of mental & physical exercise ... thank you!

If you haven't already, please read this article in Scientific American, Dec 2013:
http://www.scientificamerican.com/article/fungal-infection-accident-of-evolution-may-thrive-in-our-bodies/?page=1

What I found interesting:
(1) Fungi have much larger genomes than bacteria or viruses, and this combined with sexual reproduction, gives them a larger arsenal for rapid adaptation.
(2) In the wild, the biggest predators for this fungus are amoebas, therefore it has developed protection mechanisms. If fungus ends up in humans, marcophages look very much like amoebas, and the fungus hitches a ride inside the macrophage, protected from the immune system until it can replicate and do damage.

Maybe you can do a show on virulent fungi? TWiF? Elio should be interested …

Anne writes:

Here's an article which describes a TB drug that can be tweaked to target multiple disease-causing bacteria, and also ward off resistance by targeting multiple pathways in organisms.

http://news.illinois.edu/news/14/0417TBdrug_EricOldfield.html

[here is the paper: http://www.ncbi.nlm.nih.gov/pubmed/24568559]

Geoffrey writes:

Doctors:

I have a suggestion for a slightly out-of-the-way article that would be interesting to hear you analyze. I may be wrong but this article seems a little "primitive" and almost designed to continue an "alien origin" scenario. Despite that, this appears to be a genuine phenomenon in need of some specificity.

Personally, I'd love to learn that it is a stratospheric life form that got swept down to earth but I suspect that it is much more likely to be an oceanic life form swept up by a typhoon.

"Morphological and Molecular Analysis Calls for a Reappraisal of the Red Rain Cells of Kerala", Rajkumar Ganagappa, Mark J. Burchell, Stuart I Hogg, Current Microbiology (2014) 68: 192-198.
http://www.ncbi.nlm.nih.gov/pubmed/24071812

Geoffrey writes:
Doctors:

Regarding episode 72, I have to confess that it was one of those episodes that went, mostly, right over my head. Fortunately, I was saved by a listener's question regarding using beer as a vaccine medium against yeast infections. At least I know a little about beer.

First of all, I don't have any set answers for your querent. I do have some information that might help set the stage.

Yeasts are indeed used in the production of beer but comparing the basic beer yeast (Saccharomyces) with an infectious yeast like, say, Candida is lot like comparing the stomping power of the hyrax versus an elephant. They may be related but they're different beasts. That said, it might be possible and even practical to infect a beer wort with infectious yeasts and have them proliferate. If you could figure out some way to engineer a non-infectious version of that yeast, then I suppose that it might be possible to prime the immune system against infectious strains of that yeast. My guess is that the process is a lot tricker than with, say, polio or people would already be doing it. In addition, it would likely change the taste of the beer which might or might not be a good thing. Fermentation with non-Saccharomyces yeasts is being studied and does have some beneficial properties.

Then there is the question of actually getting the non-infectious infectious yeast or some significant immune-response-inducing part of it into the final product. If you lysed the yeasts and the appropriate vaccinating portions were soluble and smaller than the filter size, then that could work if you didn't denature it with the heating process first.

There might, however, be a simpler way. Europeans and Americans prefer their beer clear and non-yeasty so they heat it up and filter it. There is, however, a class of ancient beers called opaque or sour beers. These are simple beers which are not filtered (hence both yeasty and carbohydraty - a full meal at lunch time). They are also produced by the combined actions of yeasts and lactic acid bacteria (hence the sourness). For the most part, these beer are living beers, made in the home, and drunk within a day or two. They are best-known in Africa.

If the non-infectious infectious yeast could be supplied in a dormant state able to withstand, for instance, the hot african sun, (perhaps in a spray-dried sugar-yeast mix) then the yeast could be added to this sour beer, proliferate, and be drunk live to induce the immune response. Any taste differences would be much less noticeable in this product and it would fit in well and easily with the daily food consumption of some areas of the world.

Of course, if you could get it into a dormant state in sugar, then it might just be easier to distribute it in lollipops.

Interesting idea that probably won't work but it does lead to some interesting possibilities for integrating other medicinal microbes into diets.

Dalton writes:

Heard you mention that you had a competitor by the name of Goggles Optional, so being obsessive about science, I looked them up and tried listening to a few of their podcasts. It's reminiscent of TWIS and no real competition to your in depth science podcasting! Actually, it's a bit aggravating.


Juan writes:
Hi, I have some comments regarding your dislike of some choice of words in the microbiology and molecular fields. This discussion should be able to fit both twiv and twim.

First you say that the term prokaryote is wrong, but i think the meaning that it has widely attached to the word is wrong. Usually people think of the word to mean without nucleus, and usually we think of these organisms coming before the eukaryotes (that is another discussion altogether) but i don't find this is correct.

there are two stems pre- and pro- , both of them can be meant to mean before, but in a different way. pre- would mean to me something that happens before the appearance of anything, so cells that appeared before eukaryotes would be prekaryotes. Now, prokaryote would mean to me protokaryote, which people may have chosen to shorten to prokaryote. This fits best with the description of these organisms, since they have a nucleiod or protonucleus, some sort of organization that is not quite a nucleus but it is there. so I think prokaryote fits best if it is explained right.

The other is your dislike to the expression "a protein is expressed in the X", you say that we shouldn't say this but instead the protein is translated and that a only a gene can be expressed, and i think this is wrong as well. A gene is transcribed, a protein is translated. What i mean by wrong is that the word expressed according to (http://dictionary.reference.com/browse/express) can signify to manifest. Following this, a gene is expressed when the DNA is copied and the specific bases of the gene are put together, an mRNA is expressed when the gene is transcribed by RNAPol, and a protein can be expressed when it is translated and when it has reached its final destination.

One other comment is how we are thought about bacteria. It is regarding the fact that bacteria are thought of archaic life forms, and while the first lifeforms might have resembled more single celled organisms, both the lineage that gave rise to humans is as old as that of bacteria since we should have the same primordial ancestor, unless there were independent primordial life forms formations. Everyone should be taught that any extant organism is as "modern" as any since all organisms have to adapt to the changing and current environment. So we can say that current bacteria are the best expression of their lineage, and not that being unicellular organisms they chose to not continue to innovate biologically.

A latest topic of discussion has been the state of science, and it occurred to me that while most people in science say that cutting down the number of PhDs and restructuring, it seems contradictory the fact that there are very active programs of highschoolers and minorities into science with the excuse that we need more scientists, what are your thoughts on this?

Thanks for your discussions, I'm always looking forward for each episode of the Twimvps and also urban agriculture.

 

TWiM 80 Letters

Bob writes:

Dear TWIM hosts,

I enjoyed episode 76, "Genetic biopixels and a pathogenic sweet tooth". I really enjoyed hearing about the course that Dr. Schaechter teaches and in particular the work his students did in developing the biosensor. I would like to recommend a couple of papers that a classmate in my differential equations class told me about. They can be found at Biomed Central and are open source which is great. The first is "Solving a Hamiltonian Path Problem with a bacterial computer", Jordan Baumgardner et al, J Biol. Engineering 2009, 3:11. The second was also published in the same journal, "Engineering bacteria to solve the Burnt Pancake Problem", Karmella A. Haynes et al, J. Biol. Engineering 2008,2:8.

A Hamiltonian Path Problem involves finding a route in a directed graph that starts at a node ( the beginning node) and visits all of the nodes in the graph exactly one time. Companies like FedEx solve these kinds of problems daily in determining the most economical and efficient routes for their delivery persons. Solutions to these types of problems are very complex and computationally intensive. The authors used E. coli that contained a Hin/hixC recombination system from S. typhimurium to randomly shuffle DNA segments as the computing system. They represented nodes in the graph as linked halves of two different genes encoding red or green fluorescent proteins. The bacterial populations displayed phenotypes that reflected random ordering of the edges of the graph. A Hamiltonian path was reported by fluorescing both red and green, resulting in yellow colonies. The Burnt Pancake Problem involves sorting a stack of distinct objects into proper order and orientation using the minimum number of manipulations. This paper describes a proof-of-concept of "in vivo" computation. volunteer

I enjoy so much listening to all of the TWIV, TWIM and TWIP podcasts. Since I've been working on my math degree I don't really have anyone to talk biology, biochemistry, etc with and I miss it. I'm down to the last 2 course before I'm finished, "Real Analysis" and "Probability". I'm hoping that I can find a lab to volunteer to help out in and I've been looking but so far no one has been too keen on having a 70 year old guy hanging out in the lab. Oh well, I have had been able to take some interesting breadth classes and just finished BIoInformatics. It was a trip to actually do sequence analysis and construct heat maps and run blasts! Anyone working on a machine to reverse aging I'm a willing volunteer.

Weather in Orange CA this week has been hot and dry. Today was 98 F, 37 C, 4% humidity, dew point 4 F, winds 20 - 30 mph. We have more of the same predicted for tomorrow and into the weekend. To windy to sail, to hot to just lay around at the beach, and with the winds the surf sucks. So good time to hole up inside in the air-conditioning and enjoy some episodes of TWIM.

Dr. Robert Kelley (Bob)

Katie writes:

Dear TWiM team,

I am currently studying for my Biology degree second year exams in the UK and have listened to my first TWiM podcast today. Id like to quickly thank you as the zombie plant topic made perfect outside reading for my plant exam in a few days! I’m about to tackle the paper now.

I will continue listening for more interesting topics!

Thanks so much,
Katie.

Mark writes:
Hi folks!

I'm giving a final exam right now, then flying out to Boston for ASMCUE/ASM. Maybe I will see some of you there!

I adore this concept of parasites/pathogens/symbionts altering the behavior of their hosts. Sounds like you all do, too!

Elio had some interesting ideas about viruses and behavior.

I know that folks are short on time, but the SF writer David Brin has an old story about this, called "The Giving Plague." It's online here:

http://www.davidbrin.com/givingplague.html

Here you have a virus that causes altruistic behavior! It reminds me of the story (I'm sure it's not true) about the fellow who survives rabies. After he recovers, he is asked why he tried to bite people. He thinks for a moment and replies "It seemed like a good idea at the time."

Even though the virology may make you wince (I love SF, but the authors sometimes...well...play a little fast and loose with the actual world of science), I think you and your readers might enjoy Dave Brin's story.

I will be teaching a freshman writing course on symbioses and parasitism this Fall at my small liberal arts college, and you can rest assured I will be discussing this and related issues with them (including TWiP!). Happy for any suggestions or assistance out there!

As always, I so enjoy listening to your podcasts.

Best wishes,

Mark Martin

--
*******************************************************************
Mark O. Martin, Ph.D.
Associate Professor
Department of Biology
University of Puget Sound

Tim writes:

Dear Drs. Racaniello, Schaecter and Schmidt,

Thanks for the great episode on swabbing the environment around hospitals to check for prevalence of antibiotic resistant microbes. The idea of resistance spreading out from health care facilities seems very intuitive after hearing about it but I'd never thought of this before. It got me thinking about the number of other livestock farmers I know who have a family member that works in health care as well as helping on the farm. Could this be leading to increases in antibiotic resistant organisms in livestock or obviously vice versa?

I also found the practice of using antibiograms interesting. I had not known how doctors make decisions on which first course antibiotics to use. I will have to ask my veterinarian friends if there is an antibiogram equivalent in animal medicine.

Thanks again for another great episode and also for the TWIV bump for our AgSciToday podcast. It was much appreciated by Steph and I. Hope that nice late spring early summer weather has rolled in where you all are and that you have a few chances to get out and enjoy it. It's a balmy 18 C here in MN and finally not raining for once although it did just rain 1.25" the other day so we were due some decent weather. I'll also add a planting progress report despite that not being a typical feature on the show - we have around 60% of our hay fields seeded, 0% of our corn and 0% of our pasture ground interseeded. Usually those numbers would all be around 100% at this time. It's been another wet spring to say the least.

Tim Zweber
Zweber Farms
www.zweberfarms.com

 

TWiM 79 Letters

Matthew writes:

Dear Doctors,

After listening to the second portion of TWiM 78, talking about the presence of gram-negative nosocomials around Brooklyn, I noticed a several people wearing scrubs while at lunch near a hospital in Houston, TX. Then a thought occured to me; disease! Disease everywhere! Might part of the problem, if these microbes are moving out from the hospital, be that they're carried from a day's worn clothes? I realize I'm asking to speculate, but think this might be a good consideration for hospital policy. Houston is currently 27 C at a low 50% humidity.

Matthew Folts

P.S. I finished my sandwich. It was a pastrami ruben.

Jim writes:
Hi Folks,

"Ideas" with Paul Kennedy on the Canadian Broadcast Corp site recently ran a 54 min program about invasive species that included a short reference to rock snot. At the link find the title, "Bioinvasion: Attack of the Alien Species!," right-click (here or there) "Download Bioinvasion: Attack of the Alien Species!" to download it. I thought it, along with Prof Schmidt's comment about furry teeth, are a good intro to any program for kids about bio-films.

Jim
Smithfield, VA

Peter writes:

You have spoken before on TWiM about the potential risks of triclosan-resistant pathogens developing through its over use.

A recent open-access article from the the University of Michigan, published in mBio, looks like it may be worth a mention. The researchers conducted a study that examined the nasal passages of healthy adults, 41% of those sampled had traces of triclosan in their nasal secretions and the presence of triclosan in the secretions also correlated positively with nasal colonization by Staphylococcus aureus.

When grown in the presence of triclosan, Staphylococcus aureus was was found to be better able to attach to human proteins.

Additional experiments found that that rats exposed to triclosan were also more susceptible to nasal colonization by Staphylococcus aureus.

http://mbio.asm.org/content/5/2/e01015-13

 

TWiM 78 Letters

Del writes: (re: episode 77)

I was looking forward to this discussion, after hearing you hint about it in a previous podcast. As a practicing ID doc, I have been fascinated by the difference in pain induced by cellulitis from presumed or proven Staph or Strep infections. I see some patients whose pain resolves in a day or so after antibiotics, and some fewer patients who have a much more protracted course of pain, with tenderness to minimal touch or change in position. I have suspected that different isolates produce different toxins to explain these clinical differences, as my clinical judgement and experience argues that patient personality differences or 'pain thresholds' are simply not enough explanation for the variation I see. It also seems to "be there, or not be there," more distinctly than a simple continuum would explain. I am grateful for the basic science work being done in the field at present, and for your discussion.

Thanks to you all for the work you put into this podcast. I am learning every week, and finding connections in areas I would have never before considered.

All the best,

Del.

Del DeHart MD FACP

Associate Professor of Medicine

Michigan State University

 

 

Geoffrey writes:

 

Good Doctors:

     I realize that this is a bit behind the times but I have two questions related to beta-lactamase (hope I got that right) form episode 6 - "Antibacterial Therapy with Bacteriophage".

1) We all know that the proliferation of bacterial resistance to antibiotics has a direct influence on infection recovery in humans and animals. What I'm pretty sure most people forget is that most antibiotics began their "careers" as part of microbial defense systems. Are you folks aware of any studies looking at the effects of increasing antibiotic resistance in environmental microbiomes? I would think that this human-induced change has got to be skewing microbial populations and interactions. Indeed, I'm having trouble even imagining what the impacts on the microbial and, therefore macrobial world might be.

2) During your discussion of beta-lactamase gene development in the environment, I thought of a possible counter that might help us continue to use beta-lactam antibiotics a little longer. Are you aware of any groups who are researching anti-beta-lactamase drugs that could be added to antibiotics allowing the beta-lactams to retain some effectiveness against resistant microbes? If someone developed a low-toxicity drug that had a significantly higher and, one would like, non-reversible affinity for beta-lactamase than beta-lactam. then one could, presumably, administer it along with beta-lactam and it would inactivate the beta-lactamase while leaving the beta-lactam free to do it's work. Such a system probably wouldn't be effective within a microbe but it should be effective for running interference at cell membranes.

                                Thanks for the interesting shows,

                                Geoffrey

 

Robin writes:

 

Consolidation

Dr. Schmidt's viral illness would be quite serious if there was consolidation as was asserted.

Consolidation refers to the gross characteristics of the lung when it turns from fluffy and pliant into solid as the air spaces become filled with cellular and proteinaceous exudates in pneumonias. Bad enough with bacteria and the antibiotic resistance problem; if it is a viral pneumonia, the treatment modalities are mostly supportive care.

 

Matt writes:

 

hello,

It's been found that nasal carriage of Staphylococcus aureus is associated with increased risk of infection due to dispersal of SA from the nose while breathing and by nose-picking and not washing your hands. Some individuals are colonized with SA and are more prone to infection. Now there's a lot of research on how best to decolonize the nose of SA, because it survives antibiotics and quickly recolonizes the body. Mupirocin is typically used, but results are not good and resistance is likely. Seems to me that the aim of decolonization is stupid, since it is impossible to kill every last cell in and on the body, and even if you could there's plenty more in an individual's environment (which can survive for months on surfaces) to recolonize them anyway. Surely a better aim is to find out why some people do not become colonized and reproduce whatever they have in colonized people. Presumably, there's something about uncolonized peoples' immune systems and/or microbiomes which makes it hard for SA to become a problem. Maybe it's like the problems some people have with gut bacteria, where gut bacteria (shit) transplants have been shown to be effective. Maybe similar transplants of bacteria from the skin and/or nose of uncolonized individuals would be as effective for SA depopulation? It's a revolting idea, but no more disgusting than a poo-transplant!

 

Matthew writes:

 

Professor Racaniello

Didn't recognize "Speak friend and enter!" and "NIN" ?!? What kind of barbarians do you invite on this show?!

Just kidding. TWIM # 73 was another amazing and wonderful podcast. I am only a geologist, so I can sometimes only vaguely hum along with yours, Michele's, and Michael's biochemistry arias. Nonetheless, TWIM is one of my favorite podcasts. When I listen on my walking commute from my home to my office in Seattle, I arrive smarter!. And grateful. I am always grateful after listening. Thank you!

 

TWiM 77 Letters

Francois writes:

Hello Twim team,

After reading the Pasteur lecture.
It seems that the idea of using the Pseudomonas aer, "coal & septicemia" came from a demonstration that the "bactericidie" in the blood from animal with anthrax ("sang charbonneux") was the only origin of the disease.
It was a point of contention in the fight against the last supporters of the spontaneous generation.

When use the "sang charbonneux" from death animals collected at a rendering facility was shown to kill rabbit, but without the presence of the bactericidie in the rabbit blood.
Pasteur was able to demonstrate that was due to contamination of the corps blood between the time of death & the collection, by the "virions" causing "septicemie". And that's was causing the destruction of the "coal virulence" (virulence charbonneuse). For him it was of therapeutic interest, but it seems he has never used it on human (only on guineapigs).

He has developed instead the vaccination against anthrax by selection of an attenuated variant.

By the way fun coincidence with Michael remarque to Elio about the LON & E coli turning to snakes.

In the same lecture Pasteur also observed that outside of the blood in septicemia killed guinea pigs, the bactericidies form long snake like filament "creeping, sinuous, and separating the blood cells as a snake separate the grass in the bushes".

Best regards.

Velma writes:

Speleosalutations, TWIMologists!

I have never been as excited about a podcast as I was when I saw the title of the latest episode of TWIM (#51, Cave science with Hazel Barton), and it definitely did not disappoint! I listened to it twice right away. I'm trying to specialize in metagenomics, and I love caves and caving. If someone had asked me to design my dream TWIM, it would have been exactly like this. I had actually thought about suggesting the antibiotic resistance in cave microbes -paper for discussion, but I didn't think anyone else would find it interesting - probably because I come from a country with no proper caves, where you only get blank stares when you mention caving. Thank you so much for this episode!

I also have a question. Dr. Barton mentioned they have tried to do 454 sequencing, but apparently they haven't published anything about that yet? Do any of you know of any sequencing-based cave microbiome papers, particularly about "normal" karst caves? I've been unable to find anything on my own.

Thank you once more for the most awesome podcast episode ever,
Velma
(your subway-driving fan from Finland)

[I asked Hazel. She wrote:]

Yeah, unfortunately we've done a ton, but the papers aren't done.

Here's some good references though:

Making a living while starving in the dark: metagenomic insights into the energy dynamics of a carbonate cave. Ortiz et al, ISME J, 2013 (1-14).
Life in the dark: metagenomic evidence that a microbial slime community is driven by inorganic nitrogen metabolism. Tetu et al, ISME J, 2013(7), 1227-1236

Hazel

Pete writes:

Hi,

One of the other podcasts I listen to is CBC Radios' Quirks and Quarks. I find it always interesting, and often profound.

The segment I was just blown away by was this one: http://www.cbc.ca/quirks/2014/03/15/2014-03-15-1/.

It put together many of the keywords I have heard from your podcasts, and added a new one- "host-defence peptides".

It even made me consider what are "biofilms", a term I have heard you use but never thought significant.

So. as something different, would you consider reviewing this radio segment as you do a paper? You could bring into the discussion regular papers that are relevant, too.

And, a final question, what ARE biofilms and what are their significance?

Thanks for doing what you do (even though I understand 25% of it).

Cheers,
Pete
(Sydney, Australia),

Gian writes:

Dear Dr. Racaniello,

In your latest TWIM (#72?), I heard you wonder out loud why a virus such as polio managed just fine without virulence whereas one such as norovirus seemed to relish it.

Might the answer have something to do with the work of Dr. Graham Rook at University College, London? His Old Friends hypothesis (a re-formulated hygiene hypothesis) distinguishes between microbes that inhabited hunter-gatherer hominids before we lived in cities (like hepatitis A and H/ pylori, which protect against allergies/asthma/autoimmune diseases) and those more recently evolved to infect humans living in sufficient population densities to support epidemics (like measles, which does NOT protect against a/a/a).

Maybe virulence evolved as an adaptation to crowds?

Just a thought,
Gian

P.S. My mother's family has the name Ianiello, which means--maybe 500 years ago or so--our families may have known each other. Just another thought.

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