The oldest known anatomically modern humans in Europe

A couple of days ago, on December 1st, was the National Day of Romania, a small country in the South-East of Europe. In its honor, I dug out a paper that shows that some of the earliest known modern humans in Europe were also… dug out there.

Trinkaus et al. (2003) investigated the mandible of an individual found in 2002 by a Romanian speological expedition in Peștera cu Oase (the Cave with Bones), one of the caves in the SouthWest of the country, not far from where Danube meets the Carpathians.

First the authors did a lot of very fine measurement of various aspects of the jaw, including the five teeth, and then compared them with those found in other early humans and Neanderthals. The morphological features place the Oase 1 individual as an early modern human with some Neanderthal features. The accelerator mass spectrometry radiocarbon (14C) direct dating makes him the oldest early modern human discovered to that date in Europe; he’s 34,000–36,000 year old. I’m assuming is a he for no particular reason; the paper doesn’t specify anywhere whether they know the jaw owner’s gender and age. A later paper (Fu et al., 2015) says Oase 1 is even older: 37,000–42,000-year-old.

After this paper it seemed to be a race to see what country can boast to have the oldest human remains on its territory. Italy and UK successfully reassessed their own previous findings thusly: UK has a human maxilla that was incorrectly dated in 1989 but new dating makes it 44,200–39,000 year old, carefully titling their paper “The earliest evidence for anatomically modern humans in northwestern Europe” (Higham et al., 2011) while Italy’s remains that they thought for decades to be Neanderthal turned out to be 45,000-43,000 years old humans, making “the Cavallo human remains […] the oldest known European anatomically modern humans” (Benmazzi et al., 2011).

I wonder what prompted the sudden rush in reassessing the old untouched-for-decades fossils… Probably good old fashioned national pride. Fair enough. Surely it cannot have anything to do with the disdain publicly expressed by some Western Europe towards Eastern Europe, can it? Surely scientists are more open minded than some petty xenophobes, right?

Well, the above thought wouldn’t have even crossed my mind, nor would I have noticed that the Romanians’ discovery has been published in PNAS and the others in Nature, had it not been for the Fu et al. (2015) paper, also published in Nature. This paper does a genetic analysis of the Oase 1 individual and through some statistical inferences that I will not pretend to fully understand they arrive to two conclusions. First, Oase 1 had a “Neanderthal ancestor as recently as four to six generations back”. OK. Proof of interbreeding, nothing new here. But the second conclusion I will quote in full: “However, the Oase individual does not share more alleles with later Europeans than with East Asians, suggesting that the Oase population did not contribute substantially to later humans in Europe.”

Now you don’t need to know much about statistics or about basic logic either to know that from 1 (one) instance alone you cannot generalize to a whole population. That particular individual from the Oase population hasn’t contributed to later humans in Europe, NOT the entire population. Of course it is possible that that is the case, but you cannot scientifically draw that conclusion from one instance alone! This is in the abstract, so everybody can see this, but I got access to the whole paper, which I have read in the hopes against hope that maybe I’m missing something. Nope. The authors did not investigate any additional DNA and they reiterate that the Oase population did not contribute to modern-day Europeans. So it’s not a type-O. From the many questions that are crowding to get out like ‘How did it get past reviewers?’, ‘Why was it published in Nature (interesting paper, but not that interesting, we knew about interbreeding so what makes it so new and exciting)?’, the one that begs to be asked the most is: ‘Why would they say this, when stating the same thing about the Oase 1 individual instead about the Oase population wouldn’t have diminished their paper in any way?’ .

I must admit that I am getting a little paranoid in my older age. But with all the hate that seems to come out and about these days EVERYWHERE towards everything that is “not like me” and “I don’t want it to be like me”, one cannot but wonder… Who knows, maybe it is really just as simple as an overlooked mistake or some harmless national pride so all is good and life goes on, especially since the authors of all four papers discussed above are from various countries and institutions all across the Globe. Should that be the case, I offer my general apologies for suspecting darker motives behind these papers, but I’m not holding my breath.

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References:

1) Trinkaus E, Moldovan O, Milota S, Bîlgăr A, Sarcina L, Athreya S, Bailey SE, Rodrigo R, Mircea G, Higham T, Ramsey CB, & van der Plicht J. (30 Sep 2003, Epub 22 Sep 2003). An early modern human from the Peştera cu Oase, Romania. Proceedings of the National Academy of Sciences U S A,  100(20):11231-11236. PMID: 14504393, PMCID: PMC208740, DOI: 10.1073/pnas.2035108100. ARTICLE  | FREE FULLTEXT PDF

 2) Higham T, Compton T, Stringer C, Jacobi R, Shapiro B, Trinkaus E, Chandler B, Gröning F, Collins C, Hillson S, O’Higgins P, FitzGerald C, & Fagan M. (2 Nov 2011). The earliest evidence for anatomically modern humans in northwestern Europe. Nature. 479(7374):521-4. PMID: 22048314, DOI: 10.1038/nature10484. ARTICLE | FULLTEXT PDF via ResearchGate

3) Benazzi S, Douka K, Fornai C, Bauer CC, Kullmer O, Svoboda J, Pap I, Mallegni F, Bayle P, Coquerelle M, Condemi S, Ronchitelli A, Harvati K, & Weber GW. (2 Nov 2011). Early dispersal of modern humans in Europe and implications for Neanderthal behaviour. Nature, 479(7374):525-8. PMID: 22048311, DOI: 10.1038/nature10617. ARTICLE | FULLTEXT PDF via ResearchGate

4) Fu Q, Hajdinjak M, Moldovan OT, Constantin S, Mallick S, Skoglund P, Patterson N, Rohland N, Lazaridis I, Nickel B, Viola B, Prüfer K, Meyer M, Kelso J, Reich D, & Pääbo S. (13 Aug 2015, Epub 22 Jun 2015). An early modern human from Romania with a recent Neanderthal ancestor. Nature. 524(7564):216-9. PMID: 26098372, PMCID: PMC4537386, DOI:10.1038/nature14558. ARTICLE | FREE FULLTEXT PDF

By Neuronicus, 3 December 2016

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A third way of neuronal communication

electrical fields - CopyEvery neuroscience or biology textbook will tell you that neurons communicate with one another in two ways: via chemical synapses (one neuron releases some substances that change the membrane potential of the receiving neuron) or via electrical synapses (neurons physically share some membrane proteins that allows the electrical impulse to go from one neuron to another). (Nota bene: for the taxonomic nitpickers, I decided that the other non-conventional forms of communication, like diffusion, fall in one or the other of the two categories above).

Now Qiu et al. (2015) have some evidence that there may be another way of neuronal chatting. Long ago (in 1924), Hans Berger observed that neurons have rhythmic and spontaneous electrical activity. The rhythmic activity of an entire population of neurons is called a wave and can be detected with rudimentary tools such as EEG. Qiu et al. reasoned that the speed of such a traveling wave is too slow to be explained by conventional neuronal communication (of which we know quite a lot).

So the researchers ran some computer simulations to test if diffuse electrical fields can explain the speed of a wave, instead of the conventional fast communications. In other words, can local, weak, slow endogenous fields sweep the brain by recruiting nearby neurons? The computer simulations said it is possible, with a very slow speed of 10 cm/s.

Then they recorded the electrical activity of mouse hippocampus isolated in a Petri dish. When the researchers blocked the electrical field there was a decrease in the speed of the wave, meaning the field is required for the wave speed observed.

To be fair, this is not a new idea; even in the early eighties these fields were suggested, because the wave persisted even when the other two ways of communicating have been blocked. And in the early noughts it was shown that a neural network is much more sensitive to electrical field manipulation than individual neurons. What makes this paper interesting is that the authors show that the endogenous electrical fields are not too weak to underlie the wave, as previously thought. The work has implications for the study of epilepsy, sleep, and memory.

Reference: Qiu C, Shivacharan RS, Zhang M, & Durand DM (2 December 2015). Can Neural Activity Propagate by Endogenous Electrical Field?, Journal of Neuroscience, 35(48): 15800-15811; doi: 10.1523/JNEUROSCI.1045-15.2015 Article | Full Text via Research Gate | ScienceAlert cover

By Neuronicus, 11 February 2016

Mechanisms of stress resilience

71 stress - CopyLast year a new peer-reviewed journal called Neurobiology of Stress made its debut. The journal is published by Elsevier, who, in an uncharacteristic move, has provided Open Access for its first three issues. So hurry up and download the papers.

The very first issue is centered around the idea of resilience. That is, exposed to the same stressors, some people are more likely to develop stress-induced diseases, whereas others seem to be immune to the serious effects of stress.

Much research has been carried out to uncover the effects of chronic stress or of an exposure to a single severe stressor, which vary from cardiovascular disorders, obesity, irritable bowel syndrome, immune system dysfunctions to posttraumatic stress disorder, generalized anxiety, specific phobias, or depression. By comparison, there is little, but significant data on resilience: the ability to NOT develop those nasty stress-induced disorders. Without doubt, one reason for this scarcity is the difficulty in finding such rare subjects in our extremely stressful society. Therefore most of the papers in this issue focus on animal models.

Nevertheless, there is enough data on resilience to lead to no less that twenty reviews on the subject. It was difficult to choose one as most are very interesting, tackling various aspects of resilience, from sex differences to prenatal exposure to stress, from epigenetic to neurochemical modifications, from social inequalities to neurogenesis and so on.

So I chose for today a more general review of Pfau & Russo (2015), entitled ” Peripheral and central mechanisms of stress resilience”. After it introduces the reader to four animal models of resilience, the paper looks at the neruoendocrine responses to stress and identifies some possible chemical mediators of resilience (like certain hormones), then at the immune responses to stress (bad, bad cytokines), and finally at the brain responses to stress (surprisingly, not focusing on amygdala, hypothalamus or hippocampus, but on the dopamine system originating from ventral tegmental area).

I catalogue the review as a medium difficulty read because it requires a certain amount of knowledge of the stress field beforehand. But do check out the other ones in the issue, too!

Reference: Pfau ML & Russo SJ (1 Jan 2015). Peripheral and central mechanisms of stress resilience. Neurobiology of Stress, 1:66-79. Article | FREE PDF

By Neuronicus, 24 January 2016

Your blood is better than my blood

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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

Yeast can make morphine

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Opiates like morphine and heroin can be made at home by anybody with a home beer-brewing kit and the right strain of yeast. In 2015, two published papers and a Ph.D. dissertation described the relatively easy way to convince yeast to make morphine from sugar (the links are provided in the Reference paper). That is the bad news.

The good news is that scientists have been policing themselves (well, most of them, anyway) long before regulations are put in place to deal with technological advancements by, for example, limiting access to the laboratory, keeping things under lock and key, publishing incomplete data, and generally being very careful with what they’re doing.

Complementing this behavior, an article published by Oye et al. (2015) outlines other measures that can be put in place so that this new piece of knowledge doesn’t increase the accessibility to opiates, thereby increasing the number of addicts, which is estimated to more than 16 million people worldwide. For example, researchers can make the morphine-producing yeast dependent on unusual nutrients or engineer the existing strain to produce less-marketable varieties of opiates or prohibit the access to made-to-order DNA sequences for this type of yeast and so on.

You may very well ask “Why did the scientists made this kind of yeast anyway?”. Because some medicines are either very expensive or laborious to produce by the pharmaceutical companies, the researchers have sought a method to make these drugs more easily and cheaply by engineering bacteria, fungi, or plants to produce them for us. Insulin is a good example of an expensive and hard-to-get-by drug that we managed to engineer yeast strains to produce it for us. And opiates are still the best analgesics out there.

Reference: Oye KA, Lawson JC, & Bubela T (21 May 2015). Drugs: Regulate ‘home-brew’ opiates. Nature, 521(7552):281-3. doi: 10.1038/521281a. Article | FREE Fulltext PDF

By Neuronicus, 2 January 2016

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…

References:

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

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

I am blind, but my other personality can see

58depression-388872_960_720This 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 in biological way.

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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