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

Pic of the day: Galileo Galilei

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Over four hundred years ago, on December 28, 1612, Galileo was the first person to observe the planet Neptune.

Read the Galileo quote in Leonard Nimoy’s voice. Fans of Civilization V are familiar with his voice saying this quote when the Scientific Method is discovered in the game.

Prostaglandins in the sickness syndrome

63woman-698962_960_720When you’re sick you also feel awful: no appetite, weak, sleepy, feverish, achy, and so on. This is called, appropriately so, the sickness syndrome.

Saper, Romanovsky & Scammell (2012) wrote a beautiful review of the neural circuits underlying this collection of symptoms. In a nutshell, the immune system releases cytokines to fight the inflammation, which in turn stimulate the release of prostaglandins. Prostaglandins bind to various areas in the brain to produce the sickness syndrome symptoms. Below are outlined four simplified brain circuits which the non-specialists can skip entirely.

  1. Prostaglandins in the median preoptic nucleus lead to a cascade involving dorsomedial hypothalamus, rostral medullary raphe and finally the spinal cord to produce fever by activating the brown adipose tissue.
  2. Prostaglandins in the preoptic area lead to the inhibition of the brain’s analgesic system involving the descending projections of the periaqueductal grey to spinal cord, thus promoting achiness.
  3. Prostaglandins in the meninges result in adenosine release in nucleus accumbens and ventrolateral preoptic nucleus which, downstream, end in inhibiting the arousal system to produce sleepiness.
  4. Prostaglandins in the arcuate nucleus lead to inhibition of several hypothalamic nuclei involved in promoting feeding, thereby producing anorexia.

The sickness syndrome and the role prostaglandins play in it has tremendous adaptive role, as it promotes rest and recuperation. So don’t blame them too much. And if you’re really done feeling sick, take some non-steroid anti-inflammatory drugs, like aspirin, which inhibit the prostaglandins’ synthesis very effectively. That’s how and why NSAIDs work.

Reference: Saper CB, Romanovsky AA & Scammell TE (26 Jul 2012). Neural Circuitry Engaged by Prostaglandins during the Sickness Syndrome. Nature Neuroscience, 15(8):1088-95. doi: 10.1038/nn.3159. Article | FREE Fulltext PDF

By Neuronicus, 21 December 2015

The FIRSTS: Betz pyramidal neurons (1874)

Betz cell in the dog cortex. Copyright: RA Bergman, AK Afifi, PM Heidger, & MP D’Alessandro. Pic taken from here.

Bigger that Purkinje cerebellar neurons, the Betz pyramidal neurons (aka the giant pyramidal neurons) can have up to 100 micrometers in diameter. They are located in the fifth layer of the grey matter in the primary motor cortex. And they were discovered by a Ukrainian who did not receive the just place he deserves in the history of neuroscience, as most books on the subject ignore him. So let’s give him some attention.

Vladimir Alekseyevich Betz (1834–1894) was a professor of anatomy and a histologist at the Kiev University. Just like with Pavlov, sometimes there is nothing spectacular or weird or bizarre in the life of a great thinker. Betz was a child of a relatively wealthy family, went to good schools, then to Medical School, where he showed interest in the anatomy department. He continued his postgraduate studies in the West (that is Germany and Austria) after which he returned home where he got a position as a professor at his Alma Mater where he stayed until he died of heart problems at the age of 60.

Vladimir Alekseyevich Betz (1834 – 1894), License: PD

During his PhD, which was on the blood flow in the liver, Betz discovered an interest in histology. He was unsatisfied with the quality of the existing staining methods, so he worked for years to improve the fixation and staining methods of the brain tissue. His new methods allowed the cutting and preserving very thin slices and then he described what he saw. But Betz’s genius was in linking his cortical cytoarchitechtonic findings with physiological function, dividing the cortex into the motor and sensory areas. He also made revolutionary observations of the anatomical organization and development and various pathologies.

Original reference (which I did not find): Betz W (1874). Anatomischer Nachweis zweier Gehirncentra. Centralblatt für die medizinischen Wissenschaften. 12:578-580, 595-599.

Reference: Kushchayev SV, Moskalenko VF, Wiener PC, Tsymbaliuk VI, Cherkasov VG, Dzyavulska IV, Kovalchuk OI, Sonntag VK, Spetzler RF, & Preul MC (Jan 2012, Epub 10 Nov 2011). The discovery of the pyramidal neurons: Vladimir Betz and a new era of neuroscience. Brain, 135(Pt 1):285-300. doi: 10.1093/brain/awr276.  ArticleFREE FULLTEXT PDF

By Neuronicus, 17 December 2015

Vagus nerve stimulation improves recovery after stroke

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Vagus nerve stimulation by a wireless device implanted subcutaneously. License: PD. Credit: NIH/NIMH

A stroke is a serious medical condition that is characterized by the death of brain cells following bleeding in the brain or lack of blood supply to those cells. Three quarters of the survivors have weakness in the arm which can be permanent. Physical therapy helps, but not much.

Dawson et al. (2015) report a novel way to increase arm mobility after stroke. Previous findings in animal studies showed promising results by stimulating the vagus nerve (VNS). This nerve is the tenth out of the twelve cranial nerves and has many functions, primarily heart and digestive control. The authors implanted a small wireless device in the neck of nine stroke survivors and delivered very short (half a second) mild (0.8 mA) electrical pulses during rehabilitation therapy. Ten matched controls received rehab therapy only.

The authors measured motor recovery by several tests, one of which is Fugl–Meyer assessment-UE. At this test, the rehab only group improved by 3 points and the VNS + rehab group by about 9 points and this difference was statistically significant (I believe this scale’s upper limit is 66, but I’m not 100% sure).

Although the authors offer a possible mechanism through which VNS might produce cortical plasticity (through release of acetylcholine and norepinephrine driven by activation of nucleus tractus solitarius) the truth is that we don’t really know how it works. Nevertheless, it seems that VNS paired with rehab is better than rehab alone, and that in itself certainly warrants further studies, perhaps the next step being a fully double-blind experiment.

Reference: Dawson J, Pierce D, Dixit A, Kimberley TJ, Robertson M, Tarver B, Hilmi O, McLean J, Forbes K, Kilgard MP, Rennaker RL, Cramer SC, Walters M, & Engineer N. (Epub 8 Dec 2015). Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke. Stroke. 2016; 47:00-00. DOI: 10.1161/STROKEAHA.115.010477. Article | FREE FULLTEXT PDF

By Neuronicus, 11 December 2015

Herpes viruses infect neurons

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FIG. 3 from Jha et al. (2015). Wild-type EBV infection of primary human fetal neurons. Fluorescence microscopy was carried out at 2, 4, 6, and 8 days post infection to monitor for GFP expression (the fluorescent label). Microscopy images were captured at x20 magnification.

For some mysterious reason, whether Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) can infect neurons has not been established until now. Probably because some viruses from the same family do not infect neurons, so it was assumed that EPV and KSHV do not either.

Jha et al. (2015) cultured Sh-Sy5y neuroblastoma cells, teratocarcinoma Ntera2 neurons, and primary human fetal neurons in Petri dishes and then exposed them to these viruses. After infection, the authors did some fluorescence microscopy (they tagged the viruses with fluorescent dyes), real-time PCR (to confirm there was viral RNA in the cells), immunofluorescence assays (to see if the viral proteins are expressed) and Western blot analyses (to see if the specific viral antigens are made). All these showed that the viruses were happily multiplying in the cells.

Now here comes the significance of the study: EBV and KSHV are viruses associated with all sorts of nasty diseases like mononucleosis and cancers. EBV has also been associated with neurological disorders, like multiple sclerosis, Alzheimer’s, neuropathies, lymphomas etc. But the critical word here is “associated”. That is, they found these viruses in people suffering from those diseases. So the knowledge that these viruses infect neurons could point to a mechanism behind these associations. Unfortunately, EBV is present in 90-95% of the population of the world. Which means that you will find this virus in, let’s say, 9 out of 10 people suffering from Alzheimer’s, assuming normal distributions and random sampling. So the virus’s presence maybe completely unrelated to the disease. By the same rationale, you would find the virus in 9 out of 10 people found guilty of theft, for example. It would be then interesting to see find what is NOT associated with.

Caveat: I have not read the association studies, so my argument holds only if what they report is that people with disease X also have EBV. If they made, however, a comparisons and found out that people with disease X are significantly more likely to be infected with EBV than the ones without the disease, then the argument does not hold.

Reference: Jha HC, Mehta D, Lu J, El-Naccache D, Shukla SK, Kovacsics C, Kolson D, Robertson ES (1 Dec 2015). Gammaherpesvirus Infection of Human Neuronal Cells. MBio,  6(6). pii: e01844-15. doi: 10.1128/mBio.01844-15. Article | FREE FULLTEXT PDF | PsyPost cover

By Neuronicus, 7 December 2015

Tryptophan-rich foods and happiness

angry-woman public domainThe paper I feature today is not an experimental study, but an editorial written as a short review (5 pages). A not very good one, I’m afraid.

Neurochemical imbalances are to be found in virtual any brain disorder. Probably the most known is the serotonin depletion associated to depression, which is the main reason why SSRIs (selective serotonin reuptake inhibitors) are so widely prescribed for the disorder. With the caveats that serotonin is but one player, that it has many receptors involved in different aspects of the disease and “depression” is an umbrella term for a host of behaviors, this editorial focuses on non-pharmacological ways to address the depletion of serotonin. Noble goal, poor execution.

In a nutshell, Young (2007) argues that there are 4 ways to increase serotonin availability in the brain:
1) effortful focusing on positive things, either via psychotherapy, talk, social interactions, mediation or just mental exercises to consciously improve mood. I’m sure that the thought of trying to focus on the positive thoughts never crossed the minds of depressed people! Of course that this is how healthy people regulate their moods, everybody is sad or suffers loss at some point in their life and a lot of people snap out of it by engaging in those suggested behaviors, but the trouble with depression is that it persists despite efforts to be positive. The author should know that crying “Cheer up!” to a depressed person never works, but chances are they would feel even more alienated because they’ve tried that already!
2) exposure to bright light (3000 lux). No contention here. Light therapy is successful in treating seasonal depression. We should all get more light.
3) exercise. It’s unclear which kind, aerobic or to fatigue, but probably either would work.
4) eating tryptophan-rich foods (like meat, cheeses or eggs). Why tryptophan? Because the brain can make serotonin out of tryptophan, but serotonin itself is too big of a molecule to enter the brain (i.e. doesn’t cross the brain blood barrier). But the author admits that “although purified tryptophan increases brain serotonin, foods containing tryptophan do not” (p. 396) soooo,… then eating tryptophan-rich foods will NOT increase the serotonin. But then he goes on saying that drinking milk or eating nixtamalized corn increases serotonin (verbatim: “Acute ingestion of alpha-lactalbumin by humans can improve mood and cognition in some circumstances, presumably owing to increased serotonin” and “Breeding corn with a higher tryptophan content was shown in the 1980s to prevent pellagra; presumably, it also raised brain serotonin” p. 396-397). Utterly confusing and self-contradictory.

I also want to make a big note here:
a) there is no reliable evidence that eating tryptophan-rich foods increases the brain serotonin. Otherwise, instead of paying for Prozac, you would buy a huge bottle of tryptophan pills from the nearest dietary supplements store. Which brings me to my second point:
b) why don’t we give tryptophan supplements instead of SSRIs? Tryptophan is sold in USA as a dietary supplement which I think is a tremendously dangerous thing to allow (in most EU countries is considered a drug, so you can’t buy it from the shoddy dietary supplements stores). Because its efficacy in depression is inconclusive at best, i.e. most studies did not find significant improvements, while others showed improvement only in a subpopulation of depression sufferers. But it can induce nausea, sleepiness, confusion, depression, and even dementia symptoms and death. And interacts badly with other drugs or even with carbohydrate-rich foods, like pizza or pasta.

This is definitely not among the best papers I have read. It has many speculations supported by un-replicated studies. Or, when such studies are sparse, the reasoning relies on evolutionary speculations elevated to the rank of causal explanations (e.g. we spend so much time indoors, therefore depression is on the rise; conversely, our ancestors spent more time outside, therefore they were happier). Although I agree with Young that we should invest more research into non-pharmacological ways to improve brain dysfunctions, we need to do so in a more pragmatical manner that just telling people to think positive. Ok, rant over.

Reference: Young SN (Nov 2007). How to increase serotonin in the human brain without drugs. Journal of Psychiatry and Neuroscience, 32(6):394-399. PMID:18043762, PMCID:PMC2077351. Article | FREE FULLTEXT PDF

By Neuronicus, 3 December 2015