Your blood is better than my blood

Siamese tomatoes. Taken from here.

Parabiosis is a surgical procedure that lets two animals to share the same blood; it’s a case of reverse conjoined twins restricted to the circulatory system.

The procedure is over 150 years old and is a useful technique in physiology, though rarely used, probably due to the perceived cruelty towards the animals, although today is performed under anesthesia and aseptic condition. It delivered good data; for example, it was a parabiosis experiment with rodents that showed is not the sugar in the blood that causes cavities but the sugar in the mouth. Similarly, parabiosis has been proven useful in cancer, diabetes, and ageing research.

Scudellari (2015) wrote a News piece for Nature describing some advancements in the ageing field using the parabiosis technique. Namely, by joining the circulatory systems of a young and an old mouse, researchers have observed that the old mouse is faster, smarter, with rejuvenated muscles and glossier fur. Now the race is to find out what in the blood does it. Researchers caution that the young blood is not effectively reversing ageing, but may have factors circulating in it that promote tissue repair. Already a muscle-rejuvenating protein has been identified.

I am not going through the original papers themselves as I usually do (they are provided as links in the Reference paper). Instead, I am featuring the news piece by Scudellari because in addition of looking at parabiosis and ageing result, it also provides a nice historical account of the use of parabiosis. Enjoy!

Reference: Scudellari, M. (22 Jan 2015). Ageing research: Blood to blood. Nature, 517: 426-429. Article | FREE Fulltext PDF

By Neuronicus, 4 January 2015

Beer spoiling bacteria, oh no! But we know now how you’re made, suckers!

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Over 250 years ago today, on 31 December 1759, Arthur Guinness started brewing one of the most loved adult drinks today, the Guinness beer.

As with all food and drink products, beer can be also suffer spoiling due to various bacteria. The genomes of two of these culprits – Megasphaera cerevisiae PAT 1T and Lactobacillus brevis BSO 464 – have been sequenced in 2015 by two different groups.

Funny thing though: the papers that announce the completion of the genome sequencing (see bellow References) do not talk abut the significance of their discovery. The usual template for a biology paper (or as a matter of fact any science paper) is:

Introduction: x is important because y,
Methods and Results: here is what we did to understand x,
Conclusion: now we can better tackle y.

Not these papers, which basically say, in less than a page: “This bacterium spoils beer; here is its genome. You’re welcome!”

Well played, geneticists, well played… And we are, indeed, grateful. Oh, yes, we are…


1. Kutumbaka KK, Pasmowitz J, Mategko J, Reyes D, Friedrich A, Han S, Martens-Habbena W, Neal-McKinney J, Janagama HK, & Nadala C, Samadpour M (10 Sep 2015). Draft Genome Sequence of the Beer Spoilage Bacterium Megasphaera cerevisiae Strain PAT 1T. Genome Announcements, 3(5). pii: e01045-15. doi: 10.1128/genomeA.01045-15. Article | FREE Fulltext PDF | FREE GENOME

2. Bergsveinson J, Pittet V, Ewen E, Baecker N, & Ziola B (3 Dec 2015). Genome Sequence of Rapid Beer-Spoiling Isolate Lactobacillus brevis BSO 464. Genome Announcements, 3(6). pii: e01411-15. doi: 10.1128/genomeA.01411-15. Article | FREE Fulltext PDF | FREE GENOME

By Neuronicus, 31 December 2015

I am blind, but my other personality can see


This is a truly bizarre report.

A woman named BT suffered an accident when she was 20 years old and she became blind. Thirteen year later she was referred to Bruno Waldvogel (one of the two authors of the paper) for psychotherapy by a psychiatry clinic who diagnosed her with dissociative identity disorder, formerly known as multiple personality disorder.

The cortical blindness diagnosis has been established after extensive ophtalmologic tests in which she appeared blind but not because of damage to the eyes. So, by inference, it had to be damage to the brain. Remarkably (we shall see later why), she had no oculomotor reflexes in response to glare. Moreover, visual evoked potentials (VEP is an EEG in the occipital region) showed no activity in the primary visual area of the brain (V1).

During the four years of psychotherapy, BT showed more than 10 distinct personalities. One of them, a teenage male, started to see words on a magazine and pretty soon could see everything. With the help of hypnotherapeutic techniques, more and more personalities started to see.

“Sighted and blind states could alternate within seconds” (Strasburger & Waldvogel, 2015).

The VEP showed no or very little activity when the blind personality was “on” and showed normal activity when the sighted personality was “on”. Which is extremely curious, because similar studies in people with psychogenic blindness or anesthetized showed intact VEPs.

There are a couple of conclusions from this: 1) BT was misdiagnosed, as is unlikely to be any brain damage because some personalities could see, and 2) Multiple personalities – or dissociate identities, as they are now called – are real in the sense that they can be separated at the biological level.

The visual pathway that mediates conscious visual perception. a) A side view of the human brain with the retinogeniculocortical pathway shown inside (blue). b) A horizontal section through the brain exposing the same pathway.

Fascinating! The next question is, obviously, what’s the mechanism behind this? The authors say that it’s very likely the LGN (the lateral geniculate nucleus of the thalamus) which is the only relay between retina and V1 (see pic). It can be. Surely is possible. Unfortunately, so are other putative mechanisms, as 10% of the neurons in the retina also go to the superior colliculus, and some others go directly to the hypothalamus, completely bypassing the thalamus. Also, because it is impossible to have a precise timing on the switching between personalities, even if you MRI the woman it would be difficult to establish if the switching to blindness mode is the result of a bottom-up or a top-down modulation (i.e. the visual information never reaches V1, it reaches V1 and is suppressed there, or some signal form other brain areas inhibits V1 completely, so is unresponsive when the visual information arrives).

Despite the limitations, I would certainly try to get the woman into an fMRI. C’mon, people, this is an extraordinary subject and if she gave permission for the case study report, surely she would not object to the scanning.

Reference: Strasburger H & Waldvogel B (Epub 15 Oct 2015). Sight and blindness in the same person: Gating in the visual system. PsyCh Journal. doi: 10.1002/pchj.109.  Article | FULLTEXT PDF | Washington Post cover

By Neuronicus, 29 November 2015

Pesticides reduce pollination

Close-up of a bee with pollen flying by a flower. Credit: Jon Sullivan. License: PD

Bees have difficult times these days, what with that mysterious colony collapse disorder on top of various viral, bacterial and parasitical diseases. Of course, the widespread use of pesticides did not help the thriving of the hive, as many pesticides have various deleterious effects on the bees, from poor foraging or less reproduction to even death.

The relatively new (’90s) class of insecticide – the neonicotinoids – has been met with great hope because has low toxic effects on birds and mammals, as opposed to the organophosphates, for example. Why that should be the case, is a mystery for me, because the neonicotinoids bind to the nicotinic receptors present in both peripheral and central nervous system in an irreversible manner, which does not put the neonicotinoids in a favorable light.

Now Stanley et al. (2015) have found that exposure to the neonicotinoid thiamethoxam reduces the pollination provided by the bumblebees to apples. They checked it using 24 bumblebee colonies and the exposure was at low levels over 13 days, trying to mimic realistic in-field exposure. The apples visited by the bumblebees exposed to insecticide had 36% reduction in apple seeds.

Almost 90% of the flowering plants need pollination to reproduce, so any threat to pollination can cause serious problems. Over the paste few years, virtually all USA corn had been treated with neonicotinoids; EU banned the thiamethoxam use in 2013. And, to make matters worse, neonicotinoids are but only one class of the many toxins affecting the bees.

Related post: Golf & Grapes OR Grandkids (but not both!)

Reference: Stanley DA, Garratt MP, Wickens JB, Wickens VJ, Potts SG, & Raine NE. (Epub 18 Nov 2015). Neonicotinoid pesticide exposure impairs crop pollination services provided by bumblebees. Nature, doi: 10.1038/nature16167. Article

By Neuronicus, 21 November 2015

Will you trust a pigeon pathologist? That’s right, he’s a bird. Stop being such an avesophobe!


From Levenson et al. (2015), doi: 10.1371/journal.pone.0141357. License: CC BY 4.0

Pigeons have amazing visual skills. They can remember facial expressions, recall almost 2000 images, recognizes all the letters of the alphabet (well, even I can do that), and even tell apart a Monet form a Picasso! (ok, birdie, you got me on that one).

Given their visual prowess, Levenson et al. (2015) figured that pigeons might be able to distinguish medically-relevant images (a bit of a big step in reasoning there, but let’s go with it). They got a few dozen pigeons, starved them a bit so the birds show motivation to work for food, and started training them on recognizing malignant versus non-malignant breast tumors histology pictures. These are the same exact pictures your radiologist looks at after a mammogram and your pathologist after a breast biopsy; they were not retouched in any way for the pigeon’s benefit (except to make it more difficult, see below). Every time the pigeon pecked on the correct image, it got a morsel of food (see picture). Training continued for a few weeks on over 100 images.

For biopsies, the birds had an overwhelming performance, reaching 99% accuracy, regardless of the magnification of the picture, and for mammograms, up to 80% accuracy, just like their human counterparts. Modifying the pictures’ attributes, like rotation, compression or color lowered somewhat their accuracy, but they were still able to score only marginally less than humans and considerably better than any computer software. More importantly, the pigeons were able to generalize, after training, to correctly classify previously unseen pictures.

Let’s be clear: I’m not talking about some fancy breed here, but your common beady-eyed, suspicious-sidling, feral-looking rock pigeon. Yes, the one and only pest that receives stones and bread in equal measures, the former usually accompanied by vicious swearings uttered by those that encountered their slushy “gifts” under the shoes, on the windshield or in the coffee and the latter offered by more kindly disposed and yet utterly naive individuals in the misguided hopes of befriending nature. Columba livia by its scientific name, at the same time an exasperating pest and an excellent pathologist! Who knew?!

The authors even suggest using pigeons instead of training and paying clinicians. Hmmm… But who do I sue if my mother’s breast cancer gets missed by the bird, in one of those 1% chances? Because somehow making a pigeon face the guillotine does not seem like justice to me. Or is this yet another plot to get the clinicians off the hook for misdiagnoses? Leave the medical profession alone, birdies – is morally sensitive as it is -, and search employment in the police or Google; they always need better performance in the ever-challenging task of face-recognition in surveillance videos.

P.S. The reason why you didn’t recognized the word “avesophobe” in the title is because I just invented it, to distinguish the hate for birds from a more serious affliction, ornithophobia, the fear of birds.

Reference: Levenson RM, Krupinski EA, Navarro VM, & Wasserman EA (18 Nov 2015). Pigeons (Columba livia) as Trainable Observers of Pathology and Radiology Breast Cancer Images. PLoS One, 10(11):e0141357. doi: 10.1371/journal.pone.0141357.  Article | FREE FULLTEXT PDF

By Neuronicus, 19 November 2015

Terrorist attacks increase the male fetal loss

effelThe odds of having a baby boy decreases after terrorist attacks, natural or man-made disasters, or economical depression. There are several studies worldwide that support this finding. This is somewhat counter-intuitive, because there are anecdotal accounts that report an increase in male births after a war, presumably to make up for the lost men.

Bruckner et al. (2010) wanted to see if this decrease in the odds of a male births, also called the secondary sex ratio, is due to a failure to conceive male babies or the male fetuses die in the womb before birth. They looked at the public databases from 1996-2002 fetal deaths and births from the U.S. National Center for Health Statistics.

The results showed that in the months following the September 11, 2001 terrorist attacks the deaths of male fetuses older that 20 weeks increased significantly. The authors make reference to the communal bereavement hypothesis, which stipulates that stress increases in persons not directly affected by a tragedy. Although the effects of stress on pregnant females is well documented, why the male fetuses seem to be more susceptible to mother’s stress is unknown.

I chose to feature this paper because of the recent Paris atrocities.

Reference: Bruckner TA, Catalano R, & Ahern J. (25 May 2010). Male fetal loss in the U.S. following the terrorist attacks of September 11, 2001. BMC Public Health.;10:273. doi: 10.1186/1471-2458-10-273. Article | FREE FULLTEXT PDF

By Neuronicus, 15 November 2015

Kinesin in axon regeneration

Fig. 8 from Lu, Lakonishok, & Gelfand (2015). License: Creative Commons 2.
Fig. 8 from Lu, Lakonishok, & Gelfand (2015). License: Creative Commons 2.

The longest neuron that a human has is from the spinal cord to the tip of the toes. As a cell, it needs various proteins in various places. How is this transport done? Surely not by diffusion, the proteins would degrade or would arrive at inopportune membrane-moments (I just coined that). Molecular motors, on the other hand, are toiling proteins which haul huge cargoes for the benefit of the cell in an incredibly ingenious manner (they have feet and sticky soles and gears and so on). Notable motors are kinesin and dynein, the former brings stuff to the terminal buttons of the axon, the latter goes in the opposite direction, to the soma. They walk on a railway-like scaffold in a very funny manner, if you are to believe the simulations. Go on, I dare you, search kinesin or dynein animation on Google or YouTube and tell me then that biology is not funny.

And because no self-respectable scientist can work with the molecular motors without adding his/her contribution to the above-mentioned wealth of animations, the paper below comes with no less than 9 movies (as online supplemental material)! Lu et al. (2015) focused their attention on the role of kinesin in injured neurons. The authors dyed several types of proteins in fly neurons and then cultured the cells in a Petri dish. And then cut their axons with a glass needle. After that, they used a really fancy microscope (and a good microscopist, you should look at their pictures) to look at what happens. Which is this: the cut activates a c-Jun N-terminal kinase cascade (the cell’s response to stress), which leads to sliding of microtubules (part of cell’s cytoskeleton), which is com­pletely dependent on kinesin-1 heavy chain. This sliding initiates axonal regeneration (see picture).

I believe the kinesins and dyneins are the most charming, funny, and endearing proteins out there. Yes, I’m anthropomorphizing clumps of amino acids. I know, I’m a geek.

Reference: Lu W, Lakonishok M, & Gelfand VI (1 Apr 2015, Epub 5 Feb 2015). Kinesin-1–powered microtubule sliding initiates axonal regeneration in Drosophila cultured neurons. Molecular Biology of the Cell, 26(7):1296-307. doi: 10.1091/mbc.E14-10-1423. Article | FREE FULLTEXT PDF | Supplemental movies

Some youtube videos I mentioned before, quite accurate, too: best in show

by Neuronicus, 12 November 2015

Putative mechanism for decreased spermatogenesis following SSRI

fishThe SSRIs (selective serotonin reuptake inhibitors) are the most commonly prescribed antidepressants around the world. Whether is Prozac, Zoloft or Celexa, chances are that 1 in 4 Americans (or 1 in 10, depending on the study) will be making a decision during their lifetime to start an antidepressant course or not. And yet adherence to treatment is significantly low, as many people get off the SSRI due to their side effects, one of the main complains being sexual dysfunction in the form of low libido and pleasure.

Now a new study finds a mechanism for an even more worrisome effect of citalopram, (Celexa), an SSRI: the reduction of spermatogenesis. Prasad et al. (2015) used male zebrafish as a model and exposed them to citalopram in 3 different doses for 2- or 4-weeks period. They found out that the expression in the brain of the serotonin-related genes (trp2 and sert) and gonadotropin genes (lhb, sdhb, gnrh2, and gnrh3) were differently affected depending on the dose and durations of treatment. In the testes, the “long-term medium- and high-dose citalopram treatments displayed a drastic decrease in the developmental stages of spermatogenesis as well as in the matured sperm cell count” (p. 5). The authors also looked at how the neurons are organized and they found out that the serotonin fibers are associated with the fibers of the neurons that release gonadotropin-releasing hormone 3 (GnRH3) in preoptic area, a brain region in the hypothalamus heavily involved in sexual and parental behavior in both humans and fish.

Shortly put, in the brain, the citalopram affects gene expression profiles and fiber density of the serotonin neurons, which in turn decreases the production of GnRH3, which may account for the sexual dysfunctions that follow citalopram. In the testes, citalopram may act directly by binding to the local serotonin receptors and decrease spermatogenesis.

Reference: Prasad P, Ogawa S, & Parhar IS. (Oct 2015, Epub 8 Jul 2015). Serotonin Reuptake Inhibitor Citalopram Inhibits GnRH Synthesis and Spermatogenesis in the Male Zebrafish. Biololy of Reproduction. 93(4):102, 1-10. doi: 10.1095/biolreprod.115.129965. Article | FREE FULLTEXT PDF

By Neuronicus, 11 November 2015

The culprit in methamphetamine-induced psychosis is very likely BDNF

Psychoses. Credit: NIH (Publication Number 15-4209) & Neuronicus.
Psychoses. Credit: NIH (Publication Number 15-4209) & Neuronicus. License: PD.

Methamphetamine prolonged use may lead to psychotic episodes in the absence of the drug. These episodes are persistent and closely resemble schizophrenia. One of the (many) molecules involved in both schizophrenia and meth abuse is BDNF (brain derived neurotrophic factor), a protein mainly known for its role in neurogenesis and long-term memory.

Lower BDNF levels have been observed in schizophrenia, therefore Manning et al. (2015) wondered if it’s also involved in meth-induced psychosis. So they got normal mice and mice that were genetically engineered to express lower levels of BDNF. They gave them meth for 3 weeks, with escalating doses form one week to the next. Interestingly, no meth on weekends, which made me rapidly scroll to the beginning of the paper and confirm my suspicion that the experiments were not done in USA; if they were, the grad students would not have had the weekends off and mice would have received meth every day, including weekends. Look how social customs can influence research! Anyway, social commentary aside, after the meth injections, the researchers let the mice untroubled for 2 more weeks. And then they tested them on a psychosis test.

How do you measure psychosis in rodents? By inference, since the mouse will not grab your coat and tell you about the newly appeared hypnotizing wall pattern and the like. Basically, it was observed that psychotic people have a tendency to walk in a disorganized manner when given the opportunity to explore, a behavior that was also observed in rodents on amphetamines. This disorganized walk can be quantifies into an entropic index, which is thought to reflect occurrence of psychosis (I know, a lot of inferring. But you come up with a better model of psychosis in rodent!).

Manning et al. (2015) gave their mice amphetamine to mimic psychosis and then observed their behavior. And the results were that the genetically engineered mice to express less BDNF showed reduced psychosis (i.e. had a lower entropic index). In conclusion, the alteration of the BDNF pathway may be responsible for the development of psychosis in methamphetamine users.

Reference: Manning EE, Halberstadt AL, & van den Buuse M. (Epub 9 Oct 2015). BDNF-Deficient Mice Show Reduced Psychosis-Related Behaviors Following Chronic Methamphetamine. International Journal of Neuropsychopharmacology, 1–5. doi: 10.1093/ijnp/pyv116. Article | FREE FULLTEXT PDF

By Neuronicus, 9 November 2015

Hope for a new migraine medication

Headache clipart. Courtesy of ClipArtHut.
Headache. Courtesy of ClipArtHut.

The best current anti-migraine medication are triptans (5-HT1B/1D receptor agonists). Because these medications are contra-indicated in patients with a variety of other diseases (cardiovascular, renal, hepatic, etc.), the search for alternative drugs continues.

The heat- and pain-sensitive TRPV1 receptors (Transient Receptor Potential Vanilloid 1) localized on the trigeminal terminals (the fifth cranial nerve) have been implicated in the production of headaches. That is, if you activate them by, say, capsaicin, the same substance that gives the chili peppers their hotness, you get headaches (you’d have to eat an awful lot of peppers to get the migraine, though). On the other hand, if you block these receptors by triptans, you alleviate the migraines. All good and well, so let’s hunt for some TRPV1 antagonists, i.e. blockers. But, as theory often doesn’t meet practice, the first two antagonists that were tried were dropped in the clinical trials for lack of efficiency.

Meents et al. (2015) are giving another try to two different TRPV1 antagonists, by their fetching names of JNJ-38893777 and JNJ-17203212, respectively. Because you cannot ask a rat if it has a headache, it is very difficult to have a rodent model for migraine. Instead, researchers focused on giving rats some inflammatory soup directly into the subarachnoid space or capsaicin directly into the carotid artery, actions which they have reasons to believe produce severe headaches and some biological changes, like increase in a certain gene expression (c-fos, if you must know) in the trigeminal brain stem complex and release of the neurotransmitter calcitonin gene-related peptide (CGRP).

JNJ-17203212 got rid of all those physiological changes in a dose-dependent manner, presumably of the migraine, too. The other drug, JNJ-38893777, was effective only on the highest dose. Give these drugs a few more tests to pass, and off to the clinical trials with them. I’m joking, it takes a lot more research than just a paper between discovery and human drug trials.

Reference: Meents JE, Hoffmann J, Chaplan SR, Neeb L, Schuh-Hofer S, Wickenden A, & Reuter U (December 2015, Epub 24 June 2015). Two TRPV1 receptor antagonists are effective in two different experimental models of migraine. The Journal of Headache and Pain. 16:57. doi: 10.1186/s10194-015-0539-z. Article | FREE FULLTEXT PDF

By Neuronicus, 8 November 2015