The Benefits of Vacation

My prolonged Internet absence from the last month or so was due to a prolonged vacation. In Europe. Which I loved. Both the vacation and the Europe. Y’all, people, young and old, listen to me: do not neglect vacations for they strengthen the body, nourish the soul, and embolden the spirit.

More pragmatically, vacations lower the stress level. Yes, even the stressful vacations lower the stress level, because the acute stress effects of “My room is not ready yet”/”Jimmy puked in the car”/”Airline lost my luggage” are temporary and physiologically different from the chronic stress effects of “I’ll lose my job if I don’t meet these deadlines”/”I don’t know if I can keep my health insurance with this job”/”I’m worried for my child’s safety”/”My kids will suffer if I get a divorce”/”I can’t make the rent this month”.

Chronic stress results in a whole slew of real nasties, like cognitive, learning, and memory impairments, behavioral changes, issues with impulse control, immune system problems, weight gain, cardiovascular disease and so on and so on and so on. Even death. As I told my students countless of times, chronic stress to the body is as real and physical as a punch in the stomach but far more dangerous. So take a vacation as often as you can. Even a few days of total disconnect help tremendously.

There are literally thousands of peer-reviewed papers out there that describe the ways in which stress produces all those bad things, but not so many papers about the effects of vacations. I suspect this is due to the inherent difficulty in accounting for the countless environmental variables that can influence one’s vacation and its outcomes, whereas identifying and characterizing stressors is much easier. In other words, lack of experimental control leads to paucity of good data. Nevertheless, from this paucity, Chen & Petrick (2013) carefully selected 98 papers from both academic and nonacademic publications about the benefits of travel vacations.

These are my take-home bullet-points:

  • vacation effects last no more than a month
  • vacations reduce both the subjective perception of stress and the objective measurement of it (salivary cortisol)
  • people feel happier after taking a vacation
  • there are some people who do not relax in a vacation, presumably because they cannot ‘detach’ themselves from the stressors in their everyday life (long story here why some people can’t let go of problems)
  • vacations lower the occurrence of cardiovascular disease
  • vacations decrease work-related stress, work absenteeism, & work burnout
  • vacations increase job performance
  • the more you do on a vacation the better you feel, particularly if you’re older
  • you benefit more if you do new things or go to new places instead of just staying home
  • vacations increase overall life satisfaction

Happy vacationing!

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REFERENCE: Chen, C-C & Petrick, JF (Nov. 2013, Epub 17 Jul. 2013). Health and Wellness Benefits of Travel Experiences: A Literature Review, Journal of Travel Research, 52(6):709-719. doi: 10.1177/0047287513496477. ARTICLE | FULLTEXT PDF via ResearchGate.

By Neuronicus, 20 July 2018

Is piracy the same as stealing?

Exactly 317 year ago, Captain William Kidd was tried and executed for piracy. Whether or not he was a pirate is debatable but what is not under dispute is that people do like to pirate. Throughout the human history, whenever there was opportunity, there was also theft. Wait…, is theft the same as piracy?

If we talk about Captain “Arrr… me mateys” sailing the high seas under the “Jolly Roger” flag, there is no legal or ethical dispute that piracy is equivalent with theft. But what about today’s digital piracy? Despite what the grieved parties may vociferously advocate, digital piracy is not theft because what is being stolen is a copy of the goodie, not the goodie itself therefore it is an infringement and not an actual theft. That’s from a legal standpoint. Ethically though…

For Eres et al. (2016), theft is theft, whether the object of thievery is tangible or not. So why are people who have no problem pirating information from the internet squeamish when it comes to shoplifting the same item?

First, is it true that people are more likely to steal intangible things than physical objects? A questionnaire involving 127 young adults revealed that yes, people of both genders are more like to steal intangible items, regardless if they (the items) are cheap or expensive or the company that owned the item is big or small. Older people were less likely to pirate and those who already pirated were more likely to do so in the future.

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In a different experiment, Eres et al. (2016) stuck 35 people in the fMRI and asked them to imagine the tangibility (e.g., CD, Book) or intangibility (e.g., .pdf, .avi) of some items (e.g., book, music, movie, software). Then they asked the participants how they would feel after they would steal or purchase these items.

People were inclined to feel more guilty if the item was illegally obtained, particularly if the object was tangible, proving that, at least from an emotional point of view, stealing and infringement are two different things. An increase in the activation the left lateral orbitofrontal cortex (OFC) was seen when the illegally obtained item was tangible. Lateral OFC is a brain area known for its involvement in evaluating the nature of punishment and displeasurable information. The more sensitive to punishment person is, the more likely it is to be morally sensitive as well.

Or, as the authors put it, it is more difficult to imagine intangible things vs. physical objects and that “difficulty in representing intangible items leads to less moral sensitivity when stealing these items” (p. 374). Physical items are, well…, more physical, hence, possibly, demanding a more immediate attention, at least evolutionarily speaking.

(Divergent thought. Some studies found that religious people are less socially moral than non-religious. Could that be because for the religious the punishment for a social transgression is non-existent if they repent enough whereas for the non-religious the punishment is immediate and factual?)

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Like most social neuroscience imaging studies, this one lacks ecological validity (i.e., people imagined stealing, they did not actually steal), a lacuna that the authors are gracious enough to admit. Another drawback of imaging studies is the small sample size, which is to blame, the authors believe, for failing to see a correlation between the guilt score and brain activation, which other studies apparently have shown.

A simple, interesting paper providing food for thought not only for the psychologists, but for the law makers and philosophers as well. I do not believe that stealing and infringement are the same. Legally they are not, now we know that emotionally they are not either, so shouldn’t they also be separated morally?

And if so, should we punish people more or less for stealing intangible things? Intuitively, because I too have a left OFC that’s less active when talking about transgressing social norms involving intangible things, I think that punishment for copyright infringement should be less than that for stealing physical objects of equivalent value.

But value…, well, that’s where it gets complicated, isn’t it? Because just as intangible as an .mp3 is the dignity of a fellow human, par example. What price should we put on that? What punishment should we deliver to those robbing human dignity with impunity?

Ah, intangibility… it gets you coming and going.

I got on this thieving intangibles dilemma because I’m re-re-re-re-re-reading Feet of Clay, a Discworld novel by Terry Pratchett and this quote from it stuck in my mind:

“Vimes reached behind the desk and picked up a faded copy of Twurp’s Peerage or, as he personally thought of it, the guide to the criminal classes. You wouldn’t find slum dwellers in these pages, but you would find their landlords. And, while it was regarded as pretty good evidence of criminality to be living in a slum, for some reason owning a whole street of them merely got you invited to the very best social occasions.”

REFERENCE: Eres R, Louis WR, & Molenberghs P (Epub 8 May 2016, Pub Aug 2017). Why do people pirate? A neuroimaging investigation. Social Neuroscience, 12(4):366-378. PMID: 27156807, DOI: 10.1080/17470919.2016.1179671. ARTICLE 

By Neuronicus, 23 May 2018

How to wash SOME pesticides off produce

While EU is moving on with legislation to curtail harmful chemicals from our food, water, and air, USA is taking a few steps backwards. The most recent de-regulation concerns chlorphyrifos (CFP), a horrible pesticide banned in EU in 2008 (and in most of the world. China also prohibited its use on produce in 2016). CFP is associated with serious neurodevelopmental defects in humans and is highly toxic to the wildlife, particularly bees.

The paper that I’m covering today wanted to see if there is anything the consumer can do about pesticides in their produce. Unfortunately, they did not look at CFP. And why would they? At the time this study was conducted they probably thought, like the rest of us, that CFP is over and done with [breathe, slowly, inhale, exhale, repeat, focus].

Yang et al. (2017) bought organic Gala apples and then exposed them to two common pesticides: thiabendazole and phosmet (an organophosphate) at doses commonly used by farmers (125 ng/cm2). Then they washed the apples in three solutions: sodium bicarbonate (baking soda, NaHCO3, with the concentration of 10 mg/mL), Clorox (germicidal bleach with the concentration of 25 mg/L available chlorine) and tap water.

Before and after the washes the researchers used surface-enhanced Raman spectroscopy (which is, basically, a special way of doing microscopy) to take a closer look at the apples.

They found out that:

1) “Surface pesticide residues were most effectively removed by sodium bicarbonate (baking soda, NaHCO3) solution when compared to either tap water or Clorox bleach” (abstract).

2) The more you wash the more pesticide you remove. If you immerse apples in backing soda for 12 minutes for thiabendazole and 15 minutes for phosmet and then rinse with water there will be no detectable residue of these pesticides on the surface.

3) “20% of applied thiabendazole and 4.4% of applied phosmet penetrated into apples” (p. 9751) which cannot be removed by washing. Thiabendazole penetrates into the apple up to 80μ, which is four times more than phosmet (which goes up top 20 μm).

4) “the standard postharvest washing method with Clorox bleach solution for 2 min did not effectively remove surface thiabendazole” (p. 9748).

5) Phosmet is completely degraded by baking soda, whereas thiabenzole appears to be only partially so.

True to my nitpicking nature, I wish that the authors washed the apples in tap water for 8 minutes, not 2, like they did for Clorox and baking soda in the internal pesticide residue removal experiment. Nevertheless, the results stand as they are robust and their detection method is ultrasensitive being able to detect thiabendazole as low as 2μg/L and phosmet as low as 10 μg/L.

Thiabendazole is a pesticide that works by interfering with a basic enzymatic reaction in anaerobic respiration. I’m an aerobe so I shouldn’t worry about this pesticide too much unless I get a huge dose of it and then it is poisonous and carcinogenic, like most things in high doses. Phosmet, on the other hand, is an acetylcholinesterase (AChE) inhibitor (AChEI), meaning its effects in humans are akin to cholinergic poisoning. Normally, acetylcholine (ACh) binds to its muscarinic and nicotinic receptors in your muscles and brain for proper functioning of same. AChE breaks down ACh when is not needed any more by said muscles and brain. Therefore, an AChEI stops AChE from breaking down ACh resulting in overall more ACh than it’s good for you. Meaning it can kill you. Phosmet’s effects, in addition to, well…, death from acute poisoning, include trouble breathing, muscle weakness or tension, convulsions, anxiety, paralysis, quite possible memory, attention, and thinking impairments. Needles to say, it’s not so great for child development either. Think nerve gas, which is also an AChEI, and you’ll get a pretty good picture. Oh, it’s also a hormone mimicker.

I guess I’m back buying organic again. Long ago I have been duped for a short while into buying organic produce for my family believing, like many others, that it is pesticide-free. And, like many others, I was wrong. Just a bit of PubMed search told me that some of the “organic” pesticides are quite unpleasant. But I’ll take copper sulfate over chlorphyrifos any day. The choice is not from healthy to unhealthy but from bad to worse. I know, I know, the paper is not about CFP. I have a lot of pet peeves, alright?

Meanwhile, I gotta go make a huge batch of baking soda solution. Thanks, Yang et al. (2017)!

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REFERENCE: Yang T, Doherty J, Zhao B, Kinchla AJ, Clark JM, & He L (8 Nov 2017, Epub 25 Oct 2017). Effectiveness of Commercial and Homemade Washing Agents in Removing Pesticide Residues on and in Apples. Journal of Agricultural and Food Chemistry, 65(44):9744-9752. PMID: 29067814, doi: 10.1021/acs.jafc.7b03118. ARTICLE

By Neuronicus, 19 May 2018

Treatment for lupus

Science has trends, like everything else. Some are longer or shorter lived, depending on how many astonishing discoveries are linked to that given subject. The 2000’s were unquestionably the years of the DNA. Many a grant have been written (and granted) for whole-genome surveys of this and that. Alternative splicing followed. The ’10s saw the rise of various -omics: transcriptomics, metabolomics, proteomics etc. Then everybody and his mamma got on the cart of epigenetics. With a side of immune stuff. Now, move aside epigenetics, here comes the microbiome. And CRISPR.

That is not to say that the not so hip subjects of the bygone years are thoroughly squeezed of knowledge and we throw them aside like some dry dead end and never touch them again. Not at all, not a bit. The trends only mark the momentary believes of the purse holders about which direction the next panaceum universalis will jump from.

Here comes a groundbreaking paper on the gut microbiome. It’s groundbreaking because it comes with a cure for systemic lupus erythematosus (SLE). Possibly autoimmune hepatitis and others autoimmune diseases as well.

An autoimmune disease is a terrible malady that is often incurable and sometimes deadly. It happens when the immune system starts attacking the body. One hypothesis as to why that happens posits that after a particular infection, maybe a particularly nasty one, the immune system doesn’t stop attacking, but now in the absence of an enemy it turns on its own body in genetically susceptible individuals.

Vieira et al. (2018) worked with genetically susceptible mice. And the bombshell comes right there in the first page: after treatment with an oral antibiotic (vancomycin or ampicillin, but not neomycin), mice genetically designed to develop lupus had lower “mortality, lupus-related autoantibodies, and autoimmune manifestations” (p. 1156). Then the researchers took a closer look at the bodies of these mice and observed that 82% of the mice had spleens and livers infected with Enterococcus gallinarum, a gut bacterium that should stay in the gut. But this bacterium is capable of weakening the gut barriers by loosening the tightness of the junctions between gut cells and then migrate to liver, spleen, and lymph nodes. Its high abundance in these places triggers a systemic immune response. Then the authors force-fed some germ-free mice with E. galinarum and saw that the mice developed systemic autoimmune pathology.

As if that’s not enough of a news story, the researchers developed a vaccine against this bacterium. The vaccine is very specific (being made of heat-killed E. gallinarum) and results in reduced levels of serum autoantibodies and prolonged survival rate in the lupus-prone mice.

So people don’t quibble, and rightly so, that those are rodents and humans are not (well, most of them, anyway), the authors looked at the liver biopsies of three humans with SLE and five with autoimmune hepatitis (AIH). They were positive for E. gallinarum, but the controls, i. e. healthy humans, were not. Also, when healthy human liver cells were stimulated with E. gallinarum they displayed autoimmune responses, just like in the murine cells. Finally, you don’t have to undergo a liver biopsy to see if you’re infected with E. gallinarum, just a specific blood test to see if you have increased antibody titers against this bug (or its RNA) as most SLE and AIH patients did.

Needless to say, I am extremely happy with this paper. Who wouldn’t be?! It’s a cure paper! I know, I know, they don’t say that, but what does this sound to you?:

“Administration of oral vancomycin or an intramuscular vaccine against E. gallinarum prevent translocation, Th17/Tfh cell induction, autoantibody production and autoimmune-related mortality (Supplemental, p. 62).”

Call it a very promising cure or a highly effective treatment if you like, but it stares you in the face for what it is as it did the researchers who already patented their stuff and are currently conducting clinical trials.

Most of the paper is in the Supplemental material, not in the 4 pages and a bit in Science. So even if the paper is under the paywall, the Supplementals are not. Be ready for a 71 page worth of 167 MB of data though.

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REFERENCE: Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W, Barbieri A, Kriegel C, Mehta SS, Knight JR, Jain D, Goodman AL, Kriegel MA (9 Mar 2018). Translocation of a gut pathobiont drives autoimmunity in mice and humans.  Science, 359(6380):1156-1161. doi: 10.1126/science.aar7201. PMID: 29590047, DOI: 10.1126/science.aar7201. ARTICLE |  Supplemental Material | Yale press release

By Neuronicus, 8 April 2018

NASA, not media, is to blame for the Twin Study 7% DNA change misunderstanding

In case the title threw you out of the loop, let me pull you back in. In 2015, NASA sent Scott Kelly to the International Space Station while his twin brother, Mark, stayed on the ground. When Scott came back, NASA ran a bunch of tests on them to see how space affects human body. Some of the findings were published a few weeks ago. Among the findings, one caught the eyes of media who ran stories like:  Astronaut Scott Kelly now has different DNA to his identical twin brother after spending just a year in space (Daily Mail), Astronaut’s DNA no longer matches identical twin’s after time in space, NASA finds (Channel 3), Astronaut Scott Kelly’s genes show long-term changes after a year in space (NBC), Astronaut Scott Kelly is no longer an identical twin: How a year in space altered his DNA (Fox News), Scott Kelly Spent a Year in Space and Now His DNA Is Different From His Identical Twin’s (Time),  Nasa astronaut twins Scott and Mark Kelly no longer genetically identical after space trip (Telegraph), Astronaut’s DNA changes after spending year in space when compared to identical twin bother (The Independent), Astronaut Scott Kelly’s DNA No Longer Matches Identical Twin’s After a Year in Space (People), NASA study: Astronaut’s DNA no longer identical to his identical twin’s after year in space (The Hill), NASA astronaut who spent a year in space now has different DNA from his twin (Yahoo News), Scott Kelly: NASA Twins Study Confirms Astronaut’s DNA Actually Changed in Space (Newsweek), If you go into space for a long time, you come back a genetically different person (Quartz), Space can change your DNA, we just learned (Salon), NASA Confirms Scott Kelly’s Genes Have Been Altered By Space Travel (Tech Times), even ScienceAlert 😦 ran Scott Kelly’s DNA Is No Longer Identical to His Twin’s After a Year in Space.  And dozens and dozens more….

Even the astronauts themselves said their DNA is different and they are no longer twins:

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Alas, dear Scott & Mark Kelly, rest assured that despite these titles and their afferent stories, you two share the same DNA, still & forever. You are still identical twins until one of you changes species. Because that is what 7% alteration in human DNA means: you’re not human anymore.

So what gives?

Here is the root of all this misunderstanding:

“Another interesting finding concerned what some call the “space gene”, which was alluded to in 2017. Researchers now know that 93% of Scott’s genes returned to normal after landing. However, the remaining 7% point to possible longer term changes in genes related to his immune system, DNA repair, bone formation networks, hypoxia, and hypercapnia.” (excerpt from NASA’s press release on the Twin Study on Jan 31, 2018 (see reference).

If I wouldn’t know any better I too would think that yes, the genes were the ones who have changed, such is NASA’s verbiage. As a matter of actual fact, it is the gene expression which changed. Remember that DNA makes RNA and RNA makes protein? That’s the central dogma of molecular biology. A sequence of DNA that codes for a protein is called a gene. Those sequences do not change. But when to make a protein, how much protein, in what way, where to make this protein, which subtly different kinds of protein to make (alternative splicing), when not to make that protein, etc. is called the expression of that gene. And any of these aspects of gene expression are controlled or influenced by a whole variety of factors, some of these factors being environmental and as drastic as going to space or as insignificant as going to bed.

Some more scientifically inclined writers understood that the word “expression” was conspicuously missing from the above-mentioned paragraph and either ran clarification titles like After A Year In Space, NASA Astronaut’s Gene Expression Has Changed. Possibly Forever. (Huffington Post) or up-front rebukes like No, space did not permanently alter 7 percent of Scott Kelly’s DNA (The Verge) or No, Scott Kelly’s Year in Space Didn’t Mutate His DNA (National Geographic).

Now, I’d love, LOVE, I tell you, to jump to the throat of the media on this one so I can smugly show how superior my meager blog is when it comes to accuracy. But, I have to admit, this time is NASA’s fault. Although it is not NASA’s job to teach the central dogma of molecular biology to the media, they are, nonetheless, responsible for their own press releases. In this case, Monica Edwards and Laurie Abadie from NASA Human Research Strategic Communications did a booboo, in the words of the Sit-Com character Sheldon Cooper. Luckily for these two employees, the editor Timothy Gushanas published this little treat yesterday, right at the top of the press release:

“Editor’s note: NASA issued the following statement updating this article on March 15, 2018:

Mark and Scott Kelly are still identical twins; Scott’s DNA did not fundamentally change. What researchers did observe are changes in gene expression, which is how your body reacts to your environment. This likely is within the range for humans under stress, such as mountain climbing or SCUBA diving.

The change related to only 7 percent of the gene expression that changed during spaceflight that had not returned to preflight after six months on Earth. This change of gene expression is very minimal.  We are at the beginning of our understanding of how spaceflight affects the molecular level of the human body. NASA and the other researchers collaborating on these studies expect to announce more comprehensive results on the twins studies this summer.”

Good for you for rectifying your mistake, NASA! And good for you too the few media outlets that corrected their story like CNN who changed their title from Astronaut’s DNA no longer same as his identical twin, NASA finds to Astronaut’s gene expression no longer same as his identical twin, NASA finds.

But, seriously, NASA, what’s up with you guys keep screwing up molecular biology stuff?! Remember the arsenic-loving bacteria debacle? That paper is still not retracted  and that press release is still up on your website! Ntz, ntz, for shame… NASA, you need better understanding of basic science and/or better #Scicomm in your press releases. Hiring? I’m offering!

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REFERENCE: NASA. Edwards, M.  & Abadie, L. (Jan. 31, 2018). NASA Twins Study Confirms Preliminary Findings, Ed. Timothy Gushanas, retrieved on March 14,15, & 16, 2018. Address: https://www.nasa.gov/feature/nasa-twins-study-confirms-preliminary-findings

By Neuronicus, 16 March 2018

P.S. Sometimes is a pain to be obsessed with accuracy (cue in smallest violins). For example, I cannot stop myself from adding something just to be scrupulously correct. Since the day they were conceived, identical twins’ DNAs are starting to diverge. There are all sorts of things that do change the actual sequence of DNA. DNA can be damaged by radiation (which you can get a lot of in space) or exposure to some chemicals. Other changes are simply due to random mutations. So no twins are exactly identical, but the changes are so minuscule, nowhere near 1%, let alone 7%, that it is safe to say that their DNA is identical.

P.P.S. With all this hullabaloo about the 7% DNA change everybody glossed over and even I forgot to mention the one finding that is truly weird: the elongation of telomeres for Scott, the one that was in space. Telomeres are interesting things, they are repetitive sequences  of DNA (TTAGGG/AATCCC) at the end of the chromosomes that are repeated thousands of times. The telomere’s job is to protect the end of the chromosomes. You see, every time a cell divides the DNA copying machinery cannot copy the last bits of the chromosome (blame it on physics or chemistry, one of them things) and so some of it is lost. So evolution came up with a solution: telomeres, bits of unusable DNA that can be safely ignored and left behind. Or so we think at the moment. The length of telomeres has been implicated in some curious things, like cancer and life-span (immortality thoughts, anyone?). The most common finding is the shortening of telomeres associated with stress, but Scott’s were elongated, so that’s the first weird thing. I didn’t even know the telomeres can get elongated in living humans. But wait, there is more: NASA said that “the majority of those telomeres shortened within two days of Scott’s return to Earth”.  Now that is the second oddest thing! If I would be NASA that’s where I would put my money on, not on the gene expression patterns.

In Memoriam: Stephen Hawking

Yesterday, March 14, 2018, we lost a great mind and a decent human being. Thank you Dr. Stephen Hawking for showing us the Universe, the small and the big.

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I added his seminal doctoral thesis on the Free Resources page.

By Neuronicus, 15 March 2018

 

Naked Man orchid (Orchis Italica)

My first break after the morning chores was spent lucratively on social media. I say lucratively because I found this gem in my Twitter feed:

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Who says social media is bad for you? Besides me and many other professionals, that is.

Naturally, as any 6 year old would, I felt intrigued by the orchid’s appearance and wanted to know more about it because pareidolia is strong with this one. To my surprise, a quick PubMed search revealed 15 serious publications about the genes of this plant (oh, silly me, I shouldn’t be surprised). Most of these papers are authored by Italian researchers, obviously. Not because of what you think, dirty mind, but (probably) because the orchid is widespread in Italy, as the species name indicates. All of these papers dealt with the genetics and the transcriptome of the plant. Since I have already covered the transcriptome of tomato in the previous post I thought to let these papers be and give you, my reader, a breather from the world of heavy trascriptomics.

Instead, the self-evident name of the plant and its visually striking flower got me wondering if it was used as a cure for impotence or some other ailments of the male reproductive organs as part of the doctrine of signatures wave. Let me explain. Back in the 1500s, a guy called Theophrastus von Hohenheim, a.k.a. Paracelsus posited that plants that look like an organ are good for treating diseases of that organ. This led to the practice called doctrine of signatures, meaning the healers went gallivanting in the fields in search of various plants that resemble or ‘have a signature of’ some part of human anatomy, pluck it, ground it, and give it to the suffering patients. Needless to say – or perhaps not needless, given the increase in pseudoscience bull lately – this assumption is not only false, but also dangerous. Sure, eating walnuts to help your brain manage stress because walnuts look like brains may not make you less stressed but will not harm you either. Giving birthwort to expectant mothers on the other hand may very well end up with orphaned kids.

Sure enough, it looks like even before Paracelsus, the Naked Man orchid’s root was ground up and eaten as aphrodisiac or as erectile dysfunction cure in the entire Mediterranean basin, from Spain to Turkey, from Sicily to North Africa, which is the habitat of this plant. Luckily for the gentlemen in the Middle Ages, Orchis italica’s roots appear to be edible, or at least not toxic in the amounts ingested. I wish I could give you some original source for this information but I couldn’t find any that I could trust or in a language I could read.

For what is worth, it appears that although the species has been described by everybody with an intact fusiform gyrus (part of the brain responsible with, among other things, seeing faces where there aren’t), it was drawn formally by the famous botanist Heinrich Gustav Reichenbach in 1851. Alas, the internet is devoid of the exact volume where this momentous depiction took place, so I – and presumably you – were robbed of the pleasure of seeing how the plant was painted by someone with the most keen observational botanical eye. Reichenbach has drawn thousands upon thousands of plants in minute detail. So, even if I couldn’t find his plate for Orchis italica, I’ll leave you with some of his other works (excepts from Vols 3, 21, 23 of Icon. Fl. Germ. Helv., see REFERENCE).

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REFERENCE: Reichenbach, H. G. Ludwig (Heinrich Gottlieb Ludwig) & Reichenbach, H. G. (Heinrich Gustav) (1834-1912. [v. 1, 1850]). Icones florae Germanicae et Helveticae, simul Pedemontanae, Tirolensis, Istriacae, Dalmaticae, Austriacae, Hungaricae, Transylvanicae, Moravicae, Borussicae, Holsaticae, Belgicae, Hollandicae, ergo Mediae Europae. Iconographia et supplementum ad opera Willdenowii [et al.] .. 25 Volumes, Published by Leipzig and Gera: Friedrich Hofmeister, Ambrose Abel and Friedrich de Zezschwitz. https://doi.org/10.5962/bhl.title.6353. Most of the 24 volumes scanned courtesy of  The New York Botanical Garden, LuEsther T. Mertz Library

By Neuronicus, 12 March 2018

No Link Between Mass Shootings & Mental Illness

On Valentine’s Day another horrifying school mass shooting happened in USA, leaving 17 people dead. Just like after the other mass shootings, a lot of people – from media to bystanders, from gun lovers to gun critics, from parents to grandparents, from police to politicians – talk about the link between mental illness and mass shootings. As one with advanced degrees in both psychology and neuroscience, I am tired to explain over and over again that there is no significant link between the two! Mass shootings happen because an angry person has had enough sorrow, stress, rejection and/or disappointment and HAS ACCESS TO A MASS KILLING WEAPON. Yeah, I needed the caps. Sometimes scientists too need to shout to be heard.

So here is the abstract of a book chapter called straightforwardly “Mass Shootings and Mental Illness”. The entire text is available at the links in the reference below.

From Knoll & Annas (2015):

“Common Misperceptions

  • Mass shootings by people with serious mental illness represent the most significant relationship between gun violence and mental illness.
  • People with serious mental illness should be considered dangerous.
  • Gun laws focusing on people with mental illness or with a psychiatric diagnosis can effectively prevent mass shootings.
  • Gun laws focusing on people with mental illness or a psychiatric diagnosis are reasonable, even if they add to the stigma already associated with mental illness.

Evidence-Based Facts

  • Mass shootings by people with serious mental illness represent less than 1% of all yearly gun-related homicides. In contrast, deaths by suicide using firearms account for the majority of yearly gun-related deaths.
  • The overall contribution of people with serious mental illness to violent crimes is only about 3%. When these crimes are examined in detail, an even smaller percentage of them are found to involve firearms.
  • Laws intended to reduce gun violence that focus on a population representing less than 3% of all gun violence will be extremely low yield, ineffective, and wasteful of scarce resources. Perpetrators of mass shootings are unlikely to have a history of involuntary psychiatric hospitalization. Thus, databases intended to restrict access to guns and established by guns laws that broadly target people with mental illness will not capture this group of individuals.
  • Gun restriction laws focusing on people with mental illness perpetuate the myth that mental illness leads to violence, as well as the misperception that gun violence and mental illness are strongly linked. Stigma represents a major barrier to access and treatment of mental illness, which in turn increases the public health burden”.

REFERENCE: Knoll, James L. & Annas, George D. (2015). Mass Shootings and Mental Illness. In book: Gun Violence and Mental Illness, Edition: 1st, Chapter: 4, Publisher: American Psychiatric Publishing, Editors: Liza H. Gold, Robert I. Simon. ISBN-10: 1585624985, ISBN-13: 978-1585624980. FULLTEXT PDF via ResearchGate | FULLTEXT PDF via Psychiatry Online

The book chapter is not a peer-reviewed document, even if both authors are Professors of Psychiatry. To quiet putative voices raising concerns about that, here is a peer-reviewed paper with open access that says basically the same thing:

Swanson et al. (2015) looked at large scale (thousands to tens of thousands of individuals) data to see if there is any relationship between violence, gun violence, and mental illness. They concluded that “epidemiologic studies show that the large majority of people with serious mental illnesses are never violent. However, mental illness is strongly associated with increased risk of suicide, which accounts for over half of US firearms–related fatalities”. The last sentence is reminiscent of the finding that stricter gun control laws lower suicide rate.

REFERENCE: Swanson JW, McGinty EE, Fazel S, Mays VM (May 2015). Mental illness and reduction of gun violence and suicide: bringing epidemiologic research to policy. Annals of Epidemiology, 25(5): 366–376. doi: 10.1016/j.annepidem.2014.03.004, PMCID: PMC4211925. FULLTEXT | FULLTEXT PDF.

Further peer-reviewed bibliography (links to fulltext pdfs):

  1. Guns, anger, and mental disorders: Results from the National Comorbidity Survey Replication (NCS-R): “a large number of individuals in the United States have anger traits and also possess firearms at home (10.4%) or carry guns outside the home (1.6%).”
  2. News Media Framing of Serious Mental Illness and Gun Violence in the United States, 1997-2012: “most news coverage occurred in the wake of mass shootings, and “dangerous people” with serious mental illness were more likely than “dangerous weapons” to be mentioned as a cause of gun violence.”
  3. The Link Between Mental Illness and Firearm Violence: Implications for Social Policy and Clinical Practice: “Firearm violence is a significant and preventable public health crisis. Mental illness is a weak risk factor for violence despite popular misconceptions reflected in the media and policy”.
  4. Using Research Evidence to Reframe the Policy Debate Around Mental Illness and Guns: Process and Recommendations: “restricting firearm access on the basis of certain dangerous behaviors is supported by the evidence; restricting access on the basis of mental illness diagnoses is not”.
  5. Mental Illness, Mass Shootings, and the Politics of American Firearms: “notions of mental illness that emerge in relation to mass shootings frequently reflect larger cultural stereotypes and anxieties about matters such as race/ethnicity, social class, and politics. These issues become obscured when mass shootings come to stand in for all gun crime, and when “mentally ill” ceases to be a medical designation and becomes a sign of violent threat”.

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By Neuronicus, 25 February 2018

Tomato transcriptome

As most children, growing up I showed little appreciation for what I had, coveting instead what I did not. Now I realize how fortunate I have been to have grown up half the time in a metropolis and the other half at the countryside. At the farm. A subsistence farm, although I truly loathe the term because we were not just subsisting but thriving off the land, as we planted and harvested a bit of everything and we had a specimen or four of almost all the farm animals, from bipeds to quadrupeds.

I got on this memory lane after reading the paper of Shinozaki et al. (2018) on tomatoes. It was a difficult read for me as it was punctured by many term definition lookups since botany evolved quite steeply since the last time I checked, about 25 years or so.

Briefly, the scientists grew tomato plants in a greenhouse at Cornell, NY. They harvested the fruit from 60 plants about 5 to 50 days after the flower was at its peak (DPA, days post anthesis) following this chart:

  • Expanding [fruit] stage (harvested at 5, 10, 20, or 30 DPA)
  • Mature Green stage (full-size green fruit, ≈ 39 DPA),
  • Breaker stage (definite break in color from green to tannish-yellow with less than 10% of the surface, ≈ 42 DPA),
  • Pink stage (50% pink or red color, ≈ 44 DPA),
  • Light red stage (100% light red, ≈ 46 DPA),
  • Red ripe stage (full red for 8 days, ≈ 50 DPA).

(simplified from the Methods section, p. 10, see pic)

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Fig. 1 (partial from Shinozaki et al., 2018). A tissue/cell-based transcript profiling of developing tomato fruit. a Traced image of six targeted fruit tissues. Shaded areas of the total pericarp and the placenta were not harvested. b Traced image of five pericarp cells. c Representative pictures of harvested fruit spanning ten developmental stages. d Representative pictures of the stylar end of MG and Br stage fruit. DPA, days post anthesis; MG, mature green; Br, breaker; Pk, pink; LR, light red; RR, red ripe. Credit: DOI: 10.1038/s41467-017-02782-9. License: CC BY 4.0 IL.

Immediately after harvesting, the tomato was scanned with a micro-computed tomograph (micro-CT) to generate a 3D image of the fruit, including its internal structures. Then, the fruit was dissected by hand or laser, depending of its size, divided into various tissue types and then preserved either via snap-freezing in liquid nitrogen or standard tissue fixation for light or transmission electron microscopy. Finally, the researchers used kits to extract and analyze the RNA from their samples. And, last but not least, a lot of math & stats.

This is what I got out of it:

  1. A total of 24,660 genes were uniquely expressed in various tomato cell types and at various stages of development.
  2. The tomato ripens from within, meaning from the interior to the exterior and not the other way around.
  3. The ripening seems to be a continuous process, starting before the ‘Breaker’ stage.
  4. The ripening signals originate in the locular tissues (the goo around the seeds; it’s possible that the seeds themselves send the signals to the locular tissue to start the ripening process).
  5. The flesh of the fruit is only one part of the tomato and the most investigated, but the other types of tissue are also important. For example, some genes responsible for aroma and flavor (CTOMT1, TOMLOXC) are predominantly or even exclusively expressed in the flesh, but some genes that improve the nutritional value (SlGAD3) are expressed mostly in the placenta.
  6. The fruit can do photosynthesis, probably for the benefit of its seeds.
  7. Each developmental stage is characterized by a distinct transcriptome profile (by inference, also a distinct proteomic profile, although not necessarily in exact correspondence)
  8. Botany, like any serious science, is complicated.

Ah, I have been vindicated. By science, nonetheless! You see, in my pursuit to recapture the tomato taste of my childhood I sample various homegrown exemplars of Solanum lycopersicum derived both from more or less failed personal attempts with pots on the balcony and from various farmer’s market vendors. While I can understand – though not approve of – the industrial scale agro-growers’ practice to pick the tomatoes green, unripe and then artificially injecting them with ethylene to prolong shelf life, I completely fail to understand the picking them up when green by the sellers in the farmer’s markets. I had many surreal conversations with such vendors (I cannot call them farmers for the life of me) who more than once attempted to reassure me that 1) Everybody’s picking tomatoes green off the vine because that’s how it’s done and 2) Ripening happens on the window sill. In vain have I tried to explain the difference between ripen and rotten; in vain have I pointed out that color is only one indicator of ripening; in vain did I explain that during ripening on the vine the plant delivers certain substances to the fruit that lead to changes in the flesh composition to make it more nutritious for the future seedling, process that the aforesaid window sill does nor partake in. Alas, ultimately, my arguments (and my family’s last 400 years of farming experience) hit the wall of “I am growing tomatoes for three years now and I know what I’m doing. Are you buying or not?” As you might imagine, I end up going home frustrated and yet staring at some exorbitantly expensive and looking as sad as I feel greenish tomatoes.

For me, this is what Shinozaki et al. (2018) validated: Ripening is a complex process that involves a lot of physiological changes in the fruit, not merely some extra production of ethylene that can be conveniently supplied externally by a syringe or rotting on the window sill. Of course, there is nowhere in the paper that Shinozaki et al. (2018) say that. What they do say is this: “The ripening program is revealed as comprising gradients of gene expression, initiating in internal tissues then radiating outward, and basipetally along a latitudinal axis. We also identify spatial variations in the patterns of epigenetic control superimposed on ripening gradients” (Abstract). Tomayto, tomahto…

Now we know that… simply put, I’m right. Sometimes is good to be right. I am old enough to prefer happiness and tranquility over rightness & righteousness, but still young enough that sometimes, just sometimes, it feels good to be right. Yes, the Shinozaki et al. (2018) paper exists only for my vindication in my farmer’s market squabbles and not for providing a huge comprehensive atlas on the tomato transcriptome, along with an awesome spatiotemporal map showing the place and time of the expression of genes responsible for fruit ripening, quality traits and so on.

Good job, Shinozaki et al. (2018)!

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REFERENCE: Shinozaki Y, Nicolas P, Fernandez-Pozo N, Ma Q, Evanich DJ, Shi Y, Xu Y, Zheng Y, Snyder SI, Martin LBB, Ruiz-May E, Thannhauser TW, Chen K, Domozych DS, Catalá C, Fei Z, Mueller LA, Giovannoni JJ, & Rose JKC (25 Jan 2018). High-resolution spatiotemporal transcriptome mapping of tomato fruit development and ripening. Nature Communications, 9(1):364. PMID: 29371663, PMCID: PMC5785480, DOI: 10.1038/s41467-017-02782-9. ARTICLE | FREE FULLTEXT PDF | The Tomato Expression Atlas database

By Neuronicus, 7 February 2018

Interview with Jason D. Shepherd, PhD

During the first week of the publication, a Cell paper that I covered a couple of weeks ago has received a lot of attention from media outlets, like The Atlantic, Scicasts and Neuroscience News/University of Utah Press Release. It is not my intention to duplicate here their wonderfully done summaries and interviews; rather to provide answers to some geeky questions arisen from the minds of nerdy scientists like me.

Dr. Shepherd, you are the corresponding author of a paper published on Jan. 11 in Cell about a protein heavily involved in memory formation, called Arc. Your team and another team from University of Massachusetts, who published in the same issue of Cell, simultaneously discovered that Arc looks like and behaves like a virus. The protein “infects” nearby cells, in this case neurons, with instructions of how to make more of itself, i.e. it shuttles its own mRNA from one cell to another.

Neuronicus: Why is this discovery so important?

​Jason D. Shepherd: I think there’s a couple of big implications of this work:

  1. ​The so called “junk” DNA in our genomes that come from viruses and transposable elements actually provide source material for new genes. Arc isn’t the first example, but it’s the first prominent brain gene to have these kinds of origins.

  2. This is the first demonstration that cellular proteins are capable of assembling into capsid-like structures. This is a completely new way of thinking about communication between cells.

  3. We think there may be other genes that can also form capsids, suggesting this method of signaling is fairly common in organisms.

N: 2) When you and your colleagues compared Arc’s genetic sequence across species you concluded Arc comes from a virus that infected four-legged animals some time ago. A little time later the virus infected the flies too. When did these events occur?

​JDS: So we think the origins are from a retrotransposon not a virus. These are DNA sequences or elements that “jump” into the host genome. Think of them as primitive viruses. Indeed, these elements are thought to be the ancestors of retroviruses like HIV. The mammalian Arc gene seems to have originated ~400 million years ago, the fly about 150 million years ago. ​

N: 3) So, if Arc has been so successfully repurposed by the tetrapod and fly ancestors to add memory formation, what does that mean for the animals and insects before the infection? I understand that we move now in the realm of speculation, but who better to speculate on these things than the people who work on Arc? The question is: did these pre-infection creatures have bad and short memories? The alternate view would be that they had similar memory abilities due to a different mechanism that was replaced by Arc. Which one do you think is more likely?

​JDS: Good question. It’s certainly the case that memory capacity improved in tetrapods, but unclear if Arc is the sole reason. I suspect that Arc confers some unique aspects to brains, otherwise it would not have been so conserved after the initial insertion event, but I also think there are probably other Arc-like genes in other organisms that do not have Arc. I will also note that we are not even sure, yet, that the fly Arc is important for fly memory/learning.

N: 4) Remaining in the realm of speculation, if this intercellular mRNA transport proves to be ubiquitous for a variety of mRNAs, what does that say of the transcriptome of a cell at any given time? From a practical point of view, a cell is what is made off, meaning the ensemble of all its enzymes and proteins and so on, collectively termed transcriptome. So if a cell can just alter its neighbor’s transcriptome array, does that mean that it’s possible to alter also its function? Even more outrageously speculative, perhaps even its type? Can we make cancer cells commit suicide by shooting Arc capsules of mRNA at them?

​JDS: Yes! Cool ideas. I think this is quite likely, that these signaling extracellular vesicles can dramatically alter the state of a cell. We are obviously looking into this. ​

N: 5) Finally, in the paper, the Arc capsules containing mRNA are referred to as ACBAR (Arc Capsid Bearing Any RNA). At first I thought it was a reference to “Allahu akbar” which is Arabic for ‘God is greatest’, the allusion being “ACBAR! Our exosome is the greatest!” or “Arc Acbar! Our Arc is the greatest!”. Is this where the naming is coming from?

​JDS: No no. As I said on twitter, my lab came up with this acronym because we are all Star Wars nerds and the classic “It’s a trap!” line from general Ackbar seemed apt for something that was trapping RNA. ​

Below is the Twitter exchange Dr. Shepherd refers to:

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Dr. Shepherd, thank you for your time! And congratulations on a well done paper and a well told story. Your Methods section is absolutely great; anybody can follow the instructions and replicate your data. Somebody in your lab must have kept great records. Congratulations again!

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The ACBAR graphic is from the Cell’s abstract (©2017 Elsevier Inc.) but since it’s for comedic purposes, I’d say is fair use. Same for the Lego Ackbar.

By Neuronicus, 28 January 2018

P. S. Since I have obviously managed to annoy the #StarWars universe and twitterverse because I depicted General Ackbar using a Jedi sword when he’s not a Jedi, I thought only fair to annoy the other half of the world, the #trekkies. So here you go:

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