After 20 months, scientists find lab-dish brain cells matured at a similar rate to those of an actual infant.
- Scientists have found that cultures of embryonic brain cells mature at the same rate as a 20-month-old infant's.
- Researchers have looked to such cell structures, called "organoids," as potential models for understanding the human body's biological mechanisms.
- Their study validates the use of lab-dish organoids for research.
What organoids really are and aren't<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTY4MzgzOC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1OTEzMjc5Mn0.R1KWf66xU7CYlT3CPthA2J-xJKjZP0h0W4vx2Quxiq8/img.jpg?width=980" id="60c18" class="rm-shortcode" data-rm-shortcode-id="a496d5eb7684457c09d0139882876a8f" data-rm-shortcode-name="rebelmouse-image" data-width="1440" data-height="1080" />
A brain organoid
Credit: NIH Image Gallery/Wikimedia<p>Organoids are tissue cultures comprised of human embryonic stem cells. They start off as induced pluripotent stem cells (IPS) drawn from skin cells or blood cells before being reprogrammed to revert to an embryonic stem-cell-like state. From there, they can be exposed to chemicals that cause them to behave like a specific type of human cell.</p><p>In the case of this study, the chemicals caused them to become cerebral organoids, self-organized 3D cell structures that behave similarly to natural human brain cells. They don't grow to become full mini-brains.</p>
The promise of organoids<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTY4Mzg0MC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzMDEzODg0Nn0.AmSwbhi7wxpv1vKOX4jqOhB-pEqJNyFQzu2mhzHWTvc/img.jpg?width=980" id="92a7b" class="rm-shortcode" data-rm-shortcode-id="3746da47064a9d07ca33ddf44c5c1880" data-rm-shortcode-name="rebelmouse-image" data-width="1440" data-height="960" />
Credit: David Matos/Unsplash<p>The hope for organoids has been that they would provide researchers a way of observing human biological process in a benign, non-invasive way. Insights regarding the manner in which human cells and organs develop a disease, progress through its stages, and respond, or not, to medication, without involving actual human subjects or animal analogues could revolutionize research.</p><p>In the case of brain organoids, researchers have been hoping they can somehow be used to reveal the secrets of neurological and neurodevelopmental disorders, including epilepsy, autism and schizophrenia.</p><p>That organoids <em>could</em> be useful—though that doesn't mean that they <em>would</em> be—as a result of their permanently remaining embryonic cells. This study is a first indicator that organoids' larger promise can actually be fulfilled. </p>
An answer scientists have been hoping for<p>"This is novel," says Geschwind. "Until now, nobody has grown and characterized these organoids for this amount of time, nor shown they will recapitulate human brain development in a laboratory environment for the most part."</p><p>Now, says first author <a href="https://geschwindlab.dgsom.ucla.edu/pages/aaron-gordon" target="_blank">Aaron Gordon</a>, "We show that these 3D brain organoids follow an internal clock, which progresses in a laboratory environment in parallel to what occurs inside a living organism. This is a remarkable finding — we show that they reach post-natal maturity around 280 days in culture, and after that begin to model aspects of the infant brain, including known physiological changes in neurotransmitter signaling."</p><p>With the study verifying a 20-month maturation process, it remains to be seen how long, or how far, maturation in organoids goes. Can their cells continue to mature for years? Decades?</p><p>Even without an answer to that question, the study, says Geschwind, "represents an important milestone by showing which aspects of human brain development are modeled with the highest fidelity and which specific genes are behaving well in vitro and when best to model them. Equally important, we provide a framework based on unbiased genomic analyses for assessing how well in vitro models model in vivo development and function."</p><p>With IPS cells able to take on the roles of so many types of cells in the human body, and the new knowledge that they do in fact mature beyond their embryonic stage, researchers can feel more confident of insights into biological mechanisms organoids seem to reveal. And researchers can now better equipped to solve some of the human body's vexing mysteries.</p>
One million year old mammoth DNA more than doubles the previous record and suggests that even older genomes could be found.
- Scientists extracting DNA from mammoth teeth have set a new record for the oldest DNA ever sequenced.
- The new record holder may also be a member of a new species of mammoth, but that remains to be proven.
- The findings suggest that DNA as old as 2.6 million years old could be decoded.
Mammoth Molars<p> The DNA was taken from three sets of mammoth teeth discovered in Siberia in the 1970s. The three samples, named Krestovka, Adycha, and Chukochya, are too old for carbon dating techniques to be useful. Their ages were instead determined using methods such as <a href="https://en.wikipedia.org/wiki/Radiometric_dating" target="_blank" rel="noopener noreferrer">radiometric dating.</a> </p><p>Krestovka is the oldest of the three, dating back to about 1.1 or 1.2 million years ago. In addition to setting the record for the oldest animal to have DNA sequenced from it, Krestovka appears to be the first known example from a new lineage of mammoth. It seems to belong to another branch of the evolutionary tree that left no living decedents. However, some of its DNA also exists in the Colombian mammoth's genetics, which raises other questions.</p><p>While it is too soon to say that Krestovka is from a new mammoth species, the possibility is there. If it is, then it also suggests that the Columbia mammoth could be a hybrid species between this unknown branch and the woolly <a href="https://gizmodo.com/million-year-old-mammoth-teeth-contain-oldest-dna-ever-1846287115" target="_blank" rel="noopener noreferrer">mammoth</a>. This would be particularly exciting, as evidence for hybridization creating new species is rare.</p><p>Adycha dated back about one million years. It is thought to be a steppe mammoth, a larger, less hairy ancestor of the woolly mammoth. Steppe mammoths lived across Eurasia but were considered to be best suited for warmer climates than Siberia. Some of the DNA fragments also imply that adaptations for surviving in cooler temperatures, revealed in genes related to fat deposits, thermal regulation, and the circadian rhythm, appeared earlier in the evolutionary tree than previously thought. </p><p>Chukochya is the youngest of the three. Dated to some point between 500,000 and 800,000 years ago, it was an early example of a woolly mammoth. </p>
Why is this exciting, exactly?<iframe width="730" height="430" src="https://www.youtube.com/embed/gHbYJfwFgOU" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><p> DNA breaks down fairly quickly in most environments. Exposure to bacteria, water, ultraviolet light, or enzymes breaks it down. Even in the permafrost, where conditions are more favorable, these factors slowly whittle away at the information until little is left. That makes this find so exciting — it is remarkable that this much information endured a million years in the <a href="https://www.nytimes.com/2021/02/17/science/DNA-mammoth.html" target="_blank" rel="noopener noreferrer">ground</a>. </p><p>The previous record-holder was the DNA of a 750,000-year-old horse found in the permafrost of the <a href="https://www.sciencemag.org/news/2013/06/700000-year-old-horse-becomes-oldest-creature-sequenced-genome" target="_blank" rel="noopener noreferrer">Yukon</a>. In principle, it is possible to find DNA as old as the oldest permafrost: 2.6 million years old. Protein sequences last longer; the current <a href="https://elifesciences.org/articles/17092" target="_blank" rel="noopener noreferrer">record holder</a> is dated back to 3.8 million years but reveal much less information.</p><p>While the DNA from these mammoth teeth was quite fragmented, modern technology made putting the pieces together possible. By comparing what remained with the DNA of elephants and younger mammoth samples, the scientists could isolate the fragments that were unique to the specimen.</p><p>Ludovic Orlando, the head of the team which held the previous record, expressed his <a href="https://www.sciencemag.org/news/2021/02/mammoth-molars-yield-oldest-dna-ever-sequenced" target="_blank" rel="noopener noreferrer">excitement</a> at losing it, "I love this paper. I have been waiting since 2013 [for] our world record for the oldest genome to be broken."</p>
So do these findings mean we’re getting mammoth clones?<iframe width="730" height="430" src="https://www.youtube.com/embed/8c-EWSmOgDc" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><p> Not yet. As mentioned, these sequences are incomplete and damaged due to their age. The cloning of mammoths using more complete samples of their DNA is generally thought to be a bit <a href="https://www.washingtonpost.com/national/health-science/can-scientists-bring-mammoths-back-to-life-by-cloning/2015/02/06/2a825c8c-80ae-11e4-81fd-8c4814dfa9d7_story.html" target="_blank" rel="noopener noreferrer">unfeasible</a>. Even if it could be done, there is a question of what you'd do with the animal you've created. While some have suggested bringing the mammoths back and putting them in <a href="https://science.sciencemag.org/content/308/5723/796.1" target="_blank" rel="noopener noreferrer">Siberia</a>, the benefits of doing this remain unstated. </p><p>However, the findings shine a light on evolutionary paths previously unknown to us and prove that these methods can work on other samples, potentially including even older ones. </p><p> So, even if you're not going to see a cloned mammoth any time soon, you may see a better model of one at the natural history museum and a better picture of how life on Earth, including our species, changes over time in response to shifting environmental factors. It's a great takeaway from studying some old teeth.</p>
Imagine poisoning your rival and yourself and giving only yourself the antidote.
- The t-haplotype alleles play dirty when it comes to reaching the egg first.
- In order for their nefarious scene to work, just the right amount of a certain protein has to be present.
- Experiments with mouse sperm reveal the whole complicated story.
The weird power of the t-haplotype<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTYyODMwNy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY3MTA0MjA0MH0.xZsSkSgd5ecmxIIOK9aKZmLcTeg9lvr3Syrap8L10ao/img.jpg?width=980" id="4b95b" class="rm-shortcode" data-rm-shortcode-id="f7b27e53fc4a0215538d54331d9ec0de" data-rm-shortcode-name="rebelmouse-image" data-width="1440" data-height="759" />
Credit: ibreakstock/Adobe Stock<p>The researchers conducted experiments with mouse sperm to learn more about the properties of the t-haplotype, a group of genetic alleles that are known to appear on Chromosome 17 of mice.</p><p>Comparing the movement of mouse sperm with the t-haplotype against sperm without it, the researchers, led by first author <a href="https://www.molgen.mpg.de/4327992/alexandra-amaral" target="_blank">Alexandra Amaral</a> of MPIMG, definitively demonstrated the difference t-haplotype makes. Sperm with the gene factor progressed quickly forward, while "normal" sperm didn't exhibit the same degree of progress.</p><p>While most genes operate cooperatively with others, some don't. Among these "selfish" genes are the t-haplotype.</p><p style="margin-left: 20px;">"Genes that violate this rule by unfairly increasing their chance of transmission can gain large fitness advantages at the detriment of those that act fairly. This leads to selection for selfish adaptations and, as a result, counter-adaptations to this selfishness, initiating an arms race between these selfish genetic elements and the rest of the genome." — <a href="https://www.biorxiv.org/content/10.1101/271247v1.full.pdf" target="_blank">Jan-Niklas Runge, Anna K. Lindholm</a>, 2018</p><p>"Sperm with the t-haplotype manage to disable sperm without it," <a href="https://phys.org/news/2021-02-sperms-poison-competitors.html" target="_blank" rel="noopener noreferrer">says</a> corresponding study author <a href="https://www.molgen.mpg.de/Bernhard-Herrmann" target="_blank">Bernhard Herrmann</a>, also of MPIMG.</p><p>"The trick is that the t-haplotype 'poisons' all sperm," he explains, "but at the same time produces an antidote, which acts only in t-sperm and protects them. Imagine a marathon in which all participants get poisoned drinking water, but some runners also take an antidote."</p><p>The t-haplotype distributes a factor that distorts, or "poisons," the integrity of genetic regulatory signals. This goes out to all mouse sperm that carry the t-haplotype in the early stage of spermatogenesis. Chromosomes split as they mature, and half the sperm that retain the t-haplotype produce another factor that reverse the distortion, neutralizing the "poison." These t-sperm hold onto this antidote for themselves.</p>
Even the t-haplotype needs a friend<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTYyODM3OS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY3NTczNzAyMn0.QKkm39uWYg3I4BhurmHqtA6STnKKSdGfy_qEx8r2Nfc/img.jpg?width=980" id="19800" class="rm-shortcode" data-rm-shortcode-id="ea3e433d0ce9464a171a3426d36f6543" data-rm-shortcode-name="rebelmouse-image" data-width="913" data-height="615" />
Credit: Emw/Wikimedia<p>RAC1 acts as a molecular switch outside the sperm cell. It is known to be a protein that guides cells to different places in the body. For example, it directs white blood cells and cancer cells towards other cells that are putting out specific chemical signatures. The study suggests that RAC1 may point sperm toward an egg, helping it "sniff" out its target.</p><p>In addition, the presence of RAC1 seems to help the t-sperm carry out their sabotage. The researchers demonstrated this by introducing an RAC1 inhibitor to a mixed population of sperm. Prior to its introduction, the t-sperm in the group were "poisoning" their normal neighbors, causing them to move poorly. When the inhibitor neutralized the populations' RAC1, the t-sperms' dirty trick no longer worked, and the normal sperm began moving progressively.</p><p>However important RAC1 may be to t-sperm, too much or too little is problematic. Says Amaral, "The competitiveness of individual sperm seems to depend on an optimal level of active RAC1; both reduced or excessive RAC1 activity interferes with effective forward movement."</p><p>When females have two t-haplotypes on Chromosome 17, they are fertile. When sperm have one t-haplotype, their motility <em>may</em> be negatively affected, but when they have two, they are sterile. The researchers discovered the reason: They have much higher levels of RAC1.</p><p>At the same time, the study finds that normal sperm who aren't being held back by t-sperm stop moving progressively when RAC1 is inhibited, meaning that too little RAC1 also results in low motility.</p>
It’s a jungle in there<p>Herrmann sums up the insights the study offers:</p><p>"Our data highlight the fact that sperm cells are ruthless competitors. Genetic differences can give individual sperm an advantage in the race for life, thus promoting the transmission of particular gene variants to the next generation." </p>
The study found that people who spoke the same language tended to be more closely related despite living far apart.
- Studies focusing on European genetics have found a strong correlation between geography and genetic variation.
- Looking toward India, a new study found a stronger correlation between gene variation and language as well as
- social structure.
- Understanding social and cultural influences can help expand our knowledge of gene flow through human history.
A new kind of mother tongue<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTU0ODY2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzODQ4MjEyMH0.Ag7iKSgWxyUn6-v3wbIk7ADkxtbyiuUaodlxjRYmDkk/img.jpg?width=980" id="e0037" class="rm-shortcode" data-rm-shortcode-id="0624bd5ae5c2c18e87d89e6549ef3131" data-rm-shortcode-name="rebelmouse-image" data-width="815" data-height="450" />
A map showing the locations of 33 Indian populations alongside plot graphs showing the relations between sociolinguistic groups and genetic structures.
New dimensions for understanding ancestry<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="b2f6780bd878e2434da8e19bff5481d8"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/hu4pjmBTN2Y?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>None of this is to say that geography played no part in the ancestral gene flow of India, nor that social and cultural factors didn't influence genotypes across Europe. They most certainly did. That Nature study, for example, discovered genetic clusters in Switzerland that were language-based. And Europe's geographic distribution may have more to do with historical sociopolitical realities than environmental ones.</p><p>The point of both studies, however, is not to tie our genetic history to land or language, but to understand how genes flowed throughout historical societies.</p><p>"It sheds light on how genetics work in our society," Bose said in the same release. "This is the first model that can take into account social, cultural, environmental and linguistic factors that shape the gene flow of populations. It helps us to understand what factors contribute to the genetic puzzle that is India. It disentangles the puzzle."</p><p>With an improved knowledge of historic gene flow, scientists may be able to further biomedical research to better detect rare genetic variants, assess individual risks to certain diseases, and predict which populations may be more or less susceptible to particular drugs. By opening the avenues we use to understand our genetic history, we can hopefully advance such knowledge and understanding.</p>
Cold hands and feet? Maybe it's your anxiety.
- When we feel anxious, the brain's fight or flight instinct kicks in, and the blood flow is redirected from your extremities towards the torso and vital organs.
- According to the CDC, 7.1% of children between the ages of 3-17 (approximately 4.4 million) have an anxiety diagnosis.
- Anxiety disorders will impact 31% of Americans at some point in their lives.