Not all people with the same bad genetic makeup that predisposes them to a particular disease go and develop that disease or, at any rate, not with the same severity and prognosis. The question is why? After all, they have the same genes…
Here comes a study that answers that very important question. Eloy et al. (2016) looked at the most common pediatric eye cancer (1 in 15,000) called retinoblastoma (Rb). In the hereditary form of this cancer, the disease occurs if the child carries mutant (i.e. bad) copies of the RB1 tumour suppressor gene located on chromosome 13 (13q14). These copies, called alleles, are inherited by the child from the mother or from the father. But some children with this genetic disadvantage do not develop Rb. They should, so why not?
The authors studied 57 families with Rb history. They took blood and tumour samples from the participants and then did a bunch of genetic tests: DNA, RNA, and methylation analyses.
They found out that when the RB1 gene is inherited from the mother, the child has only 9.7% chances of developing Rb, but when the gene is inherited from the father the child has only 67.5% chances of developing Rb.
The mechanism for this different outcomes may reside in the differential methylation of the gene. Methylation is a chemical process that suppresses the expression of a gene, meaning that less protein is produced from that gene. The maternal gene had less methylation, meaning that more protein was produced, which was able to offer some protection against the cancer. Seems counter-intuitive, you’d think less bad protein is a good thing, but there is a long and complicated explanation for that, which, in a very simplified form, posits that other events influence the function of the resultant protein.
Again, epigenetics seem to offer explanations for pesky genetic inheritance questions. Epigenetic processes, like DNA methylation, are modalities through which traits can be inherited that are not coded in the DNA itself.
Reference: Eloy P, Dehainault C, Sefta M, Aerts I, Doz F, Cassoux N, Lumbroso le Rouic L, Stoppa-Lyonnet D, Radvanyi F, Millot GA, Gauthier-Villars M, & Houdayer C (29 Feb 2016). A Parent-of-Origin Effect Impacts the Phenotype in Low Penetrance Retinoblastoma Families Segregating the c.1981C>T/p.Arg661Trp Mutation of RB1. PLoS Genetics, 12(2):e1005888. eCollection 2016. PMID: 26925970, PMCID: PMC4771840, DOI: 10.1371/journal.pgen.1005888. ARTICLE | FREE FULLTEXT PDF
Today we celebrate the first instance the humankind stepped on the Moon. I thought only fitted to remind you of the last human there, too. As a bitter-sweet reminder that NASA is not something where budgetary concerns should lie.
Few people know that Pokemon refers not only to a game, but also to a gene. An oncogene, to be precise, with a rather strange story.
An oncogene is a gene that promotes cancer (from oncology). Conventionally, a gene name is written in lowercase italicized letters (pokemon), whereas the protein the gene makes is not italicized (POKEMON, Pokemon, or pokemon, depending on the species). Maeda et al. (2005) first established in a Petri dish that the Pokemon is required for the growth of malignant tumors. Then, through a series of classic molecular biology experiments, the scientists found out how exactly Pokemon acts to accomplish this (by suppressing the expression of anti-cancer genes). Next, they engineered mice with pokemon overexpressed and saw that the mice with a lot of Pokemon “developed aggressive tumours” (p. 282). Then the authors checked how is this gene behaving in human cancers and found out that “Pokemon is expressed at very high levels in a subset of human lymphomas” (p. 284).
And here is how the gene got its name, according to Pier Paolo Pandolfi, the leader of the research group. Bear with me because it’s complicated. [*Takes deep breath*]: PO in POK stands for POZ domain (poxvirus and zinc finger) and K in POK stands for Krüppel (zinc finger transcription factor) whereas EMON stands for erythroid myeloid ontogenic factor. POK-EMON. Simple, eh? Phew…
Truth be told, Pandolfi first named the gene pokemon at a conference in 2001 (Simonite, 2005). Then the name has been used by researchers at various scientific meetings and poster presentations.
But when the Maeda et al. paper was published in Nature in 2005 which discovered the mechanism through which the gene promotes cancer, a lot of people, scientists and journalists alike, in an attempt at humour, flooded the internet with eye-catching titles along the lines of “Pokemon causes cancer”, “Pokemon kills you” and the like. I mean, even the researchers themselves in the abstract of the paper state: “Pokemon is aberrantly overexpressed in human cancers”. In response, The Pokémon Company threatened to sue for trademark copyright infringement because they didn’t want the game to be associated with cancer, like the gene is, even if the researches said the name is an acronym (maybe they meant backronym?). In the end, the researchers changed the name of the pokemon gene to the far less enticing zbtb7.
As the question mark in the title of the post suggests, the pokeman gene may not be entirely dead yet because there are stubborn scientists that still use the name pokemon and not zbtb7. I hope they have the cash to take on Nintendo if they decide to sue after all.
Too bad the zbtb7 (a.k.a. pokemon) gene was not a beneficial gene… Because another group of researchers named their new-found gene in 2008 pikachurin and so far, Nintendo din not make any waves… That is, probably, because Pikachurin is a protein in the eye retina that is required for proper vision by speeding the electric signals. Zip zip zip Pikachurin goes…
Maeda T, Hobbs RM, Merghoub T, Guernah I, Zelent A, Cordon-Cardo C, Teruya-Feldstein J, & Pandolfi PP (20 Jan 2005). Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature, 433(7023):278-85. PMID: 15662416, DOI: 10.1038/nature03203. ARTICLE | FULLTEXT PDF at Univ. Barcelona
Simonite T (15 Dec 2005). Pokémon blocks gene name. Nature, 438(7070):897. PMID: 16355177, DOI: 10.1038/438897a. ARTICLE
There are some neurons in the human brain that fire both when the person is doing some behavior and when watching that behavior performed by someone else. These cells are called mirror neurons and were first discovered in 1988 (see NOTE) by a group of researchers form the University of Parma, Italy, led by Giacomo Rizzolatti.
The discovery was done by accident. The researchers were investigating the activity of neurons in the rostral part of the inferior premotor cortex (riPM) of macaque monkeys with electrophysiological recordings. They placed a box in front of the monkey which had various objects in it. When the monkey pressed a switch, the content of the box was illuminated, then a door would open and the monkey reached for an object. Under each object was hidden a small piece of food. Several neurons were discharging when the animal was grasping the object. But the researchers noticed that some of these neurons ALSO fired when the monkey was motionless and watching the researcher grasping the objects!
The authors then did more motions to see when exactly the two neurons were firing, whether it’s related to the food or threatening gestures and so on. And then they recorded from some 182 more neurons while the monkey or the experimenter were performing hand actions with different objects. Importantly, they also did an electromyogram (EMG) and saw that when the neurons that were firing when the monkey was observing actions, the muscles did not move at all.
They found that some neurons responded to both when doing and seeing the actions, whereas some other neurons responded only when doing or only when seeing the actions. The neurons that are active when observing are called mirror neurons now. In 1996 they were identified also in humans with the help of positron emission tomography (PET).
It is tragicomical that the authors first submitted their findings to the most prestigious scientific journal, Nature, believing that their discovery is worth it, and rightfully so. But, Nature rejected their paper because of its “lack of general interest” (Rizzolatti & Fabbri-Destro, 2010)! Luckily for us, the editor of Experimental Brain Research, Otto Creutzfeld, did not share Nature‘s opinion.
Thousands of experiments followed the tremendous discovery of mirror neurons, even trying to manipulate their activity. Many researchers believe that the activity of the mirror neurons is fundamental for understanding the intentions of others, the development of theory of mind, empathy, the process of socialization, language development and even human self-awareness.
NOTE: Whenever possible, I try to report both the date of the discovery and the date of publication. Sometimes, the two dates can differ quite a bit. In this case, the discovery was done in 1988 and the publishing in 1992.
di Pellegrino G, Fadiga L, Fogassi L, Gallese V, & Rizzolatti G (October 1992). Understanding motor events: a neurophysiological study. Experimental Brain Research, 91(1):176-180. DOI: 10.1007/BF00230027. ARTICLE | Research Gate FULLTEXT PDF
Rizzolatti G & Fabbri-Destro M (Epub 18 Sept 2009; January 2010). Mirror neurons: From discovery to autism. Experimental Brain Research, 200(3): 223-237. DOI: 10.1007/s00221-009-2002-3.ARTICLE | Research Gate FULLTEXT PDF
Yesterday I stumbled across a paper for which I had no choice but to cover. Absolutely no choice, given the oddity and novelty and, not to put a too fine point on it… uniqueness of it. Because, I have to tell you, I haven’t seen a more bizarre author affiliation in an academic journal for a scholar paper.
It’s not a fundamental research paper, but a review. It’s not exactly a regular science paper either, it’s more of a policy paper. Nevertheless, it has a rationale, sets objectives, analyzes the available evidence, draws conclusions upon observed data, and ends up with the all-too-familiar section of future directions. It even has acknowledgments and a regular size reference section. It was pre-published 4 days ago in the Journal of the American Medical Association (JAMA) and in this short interval has gained a whooping 6480 Altmetric score (meaning thousands of media outlets are talking about it) and over half million views, despite the fact that it has not been peer-reviewed (but it was fact-checked for 2 months).
The paper analyzes data spanning more than 50 years (from 1963 to 2016) regarding the healthcare in United States of America. The author claims that the data show that the Affordable Care Act, a major health reform passed on March 23, 2010 in USA, has led to, among other things, a dramatic decrease in the number of uninsured individuals. The paper finishes by outlining several issues that the policy makers face in the future.
So what makes it so special? The author, ladies and gentleman, is none other then the President of the United States, Barack Obama. Thus becoming the first president that published an academic paper in a scientific journal. There were previous commentaries or speeches published in scientific journals by other presidents, but this is the first scholarly paper done by a sitting President, as far as I know. Please do check out the pictures below (which are copyrighted to JAMA, by the way). I wonder if I call or write to the corresponding author I get to correspond… with the corresponding author or the Press Office…
Reference: Obama, B [Epub July 2016]. United States Health Care Reform: Progress to Date and Next Steps. JAMA. doi:10.1001/jama.2016.9797. ARTICLE | FREE FULLTEXT PDF (press the PDF button on the upper right on the JAMA page | Conflict of Interest Disclosures
A few decades ago, Italian researchers from the University of Parma discovered some neurons in monkey which were active not only when the monkey is performing an action, but also when watching the same action performed by someone else. This kind of neuron, or rather this particular neuronal behavior, had been subsequently identified in humans scattered mainly within the frontal and parietal cortices (front and top of your head) and called the mirror neuron system (MNS). Its role is to understand the intentions of others and thus facilitate learning. Mind you, there are, as it should be in any healthy vigorous scientific endeavor, those who challenge this role and even the existence of MNS.
Hobson & Bishop (2016) do not question the existence of the mirror neurons or their roles, but something else. You see, proper understanding of intentions, actions and emotions of others is severely impaired in autism or some schizophrenias. Correspondingly, there have been reports saying that the MNS function is abnormal in these disorders. So if we can manipulate the neurons that help us understanding others, then we may be able to study the neurons better, and – who knows? – maybe even ‘switch them on’ and ‘off’ when needed (Ha! That’s a scary thought!).
Anyway, previous work said that recording a weak Mu frequency in the brain regions with mirror neurons show that these neurons are active. This frequency (between 8-13 Hz) is recorded through electroencephalography (EEG). The assumption is as follows: when resting, neurons fire synchronously; when busy, they fire each to its own, so they desynchronize, which leads to a reduction in the Mu intensity.
All well and good, but there is a problem. There is another frequency that overlaps with the Mu frequency and that is the Alpha band. Alpha activity is highest when a person is awake with eyes closed, but diminishes when the person is drowsy or, importantly, when making a mental effort, like paying great attention to something. So, if I see a weak Mu/Alpha frequency when the subject is watching someone grabbing a pencil, is that because the mirror neurons are active or because he’s sleepy? There are a few gimmicks to disentangle between the two, from the setup of the experiment in such a way that it requires same attention demand over tasks to the careful localization of the origin of the two waves (Mu is said to arise from sensoriomotor regions, whereas Alpha comes from more posterior regions).
But Hobson & Bishop (2016) argue that this disentangling is more difficult than previously thought by carrying out a series of experiments where they varied the baseline, in such a way that some were more attentionally demanding than others. After carefully analyzing various EEG waves and electrodes positions in these conditions, they conclude that “mu suppression can be used to index the human MNS, but the effect is weak and unreliable and easily confounded with alpha suppression“.
What makes this paper interesting to me, besides its empirical findings, is the way the experiment was conducted and published. This is a true hypothesis driven study, following the scientific method step by step, a credit to us all scientists. In other words, a rare gem. A lot of other papers are trying to make a pretty story from crappy data or weave some story about the results as if that’s what they went for all along when in fact they did a bunch of stuff and chose what looked good on paper.
Let me explain. As a consequence of the incredible pressure put on researchers to publish or perish (which, believe me, is more than just a metaphor, your livelihood and career depend on it), there is an alarming increase in bad papers, which means
papers with inappropriate statistical analyses (p threshold curse, lack of multiple comparisons corrections, like the one brilliantly exposed here),
papers with huge databases in which some correlations are bound to appear by chance alone and are presented as meaningful (p-hacking or data fishing),
papers without enough data to make a meaningful conclusion (lack of statistical power),
papers that report only good-looking results (only positive results required by journals),
papers that seek only to provide data to reinforce previously held beliefs (confirmation bias)
and so on.
For these reasons (and more), there is a high rate of rejection of papers submitted to journals (about 90%), which means more than just a lack of publication in a good journal; it means wasted time, money and resources, shattered career prospects for the grad students who did the experiments and threatened job security for everybody involved, not to mention a promotion of distrust of science and a disservice to the scientific endeavor in general. So some journals, like Cortex, are moving toward a system called Registered Report, which asks for the rationale and the plan of the experiment before this is conducted, which should protect against many of the above-mentioned plagues. If the plan is approved, the chances to get the results published in that journal are 90%.
This is one of those Registered Report papers. Good for you, Hobson & Bishop!
Reference: Hobson HM & Bishop DVM (Epub April 2016). Mu suppression – A good measure of the human mirror neuron system?. Cortex, doi: 10.1016/j.cortex.2016.03.019 ARTICLE | FREE FULLTEXT PDF | RAW DATA