Grid View

microRNAs – tiny but potent

As we eagerly look ahead to 2025 and the scientific breakthroughs it may bring, let’s take a final look at 2024. In October the Nobel Prize in Physiology or Medicine was awarded to Victor Ambros and Gary Ruvkun. At that moment, the spotlight was turned on microRNAs (miRNAs) – tiny but powerful RNA molecules, whose discovery over 30 years ago reshaped our understanding of gene regulation.

First discovered in the 1 mm-long roundworm Caenorhabditis elegans (C. elegans)—widely used as a model organism in laboratories around the world, miRNAs quickly became recognized as evolutionarily conserved, meaning they are common in many different organisms, including humans.

While the flow of genetic information from DNA to messenger RNA (mRNA), which is then translated into proteins, explains how the information in our genomes is expressed, it does not explain how our cells become so different from one another – like blood cells, neurons, or gut cells – or how we can fight viruses and adapt to a changing environment.

One solution to this puzzle is the regulation of genetic information at multiple levels, making certain genes more active in specific cell types or under different conditions. This is where  microRNAs comes to play: a new type of very short RNAs, only 21-23 nucleotides long. Unlike mRNAs, microRNAs do not encode proteins. Instead, they bind to mRNA, preventing the translation of these mRNA sequences into proteins. In this way, microRNAs can control the amount of protein translated from a specific sequence of mRNA.

There are over a thousand genes encoding microRNAs in the human genome, and years of research have shown that cells, tissues, and organisms cannot develop properly without them. Any perturbations in microRNA expression or the cellular machinery responsible for their production can have deleterious consequences for an organism, potentially leading to diseases such as cancer, autoimmunity, or diabetes.

The discovery of microRNAs has not only transformed our understanding of gene regulation but also positioned microRNAs as potentially valuable therapeutic targets and diagnostic biomarkers. Some biotech companies are working to develop therapies that can mimic or silence microRNAs in diseases where their function is compromised. However, challenges like off-target effects complicate the development of such therapies, making their widespread use still a long way off. Moreover, microRNA expression is specific to various diseases, including cancer. Analysis of microRNAs in patient samples not only enables early detection and more accurate diagnosis, but also may predict treatment responses. Indeed, microRNA panels are already available to clinicians.

From an unassuming worm to cancer diagnostics, this is the true beauty of science. To read the full story behind Nobel Prize-worthy discovery of miRNAs, visit: https://www.nobelprize.org/prizes/medicine/2024/press-release/

This entry was posted in

Nobel Prizes

Comments

0 Comments Leave a comment

Oxygen For All: Artificial Red Blood Cells

Blood is essential to maintain human life. Through blood circulation, nutrients that are absorbed in the digestive system and the oxygen captured in the lungs are distributed across all organs.

However, life can be suddenly threatened when there is a reduction in oxygen transport due to severe blood loss. While blood transfusion is the most common alternative, shortage in blood stocks, compatibility issues (for more on this please visit post transfusion) and the short life of blood cells are still challenges to overcome. In addition, in countries where infectious diseases, such as AIDS, affect many citizens, blood donations are rare.  

Knowing this, scientists have been developing artificial products that are being tested to ensure oxygen-delivery in emergency situations. 

Oxygen transport is achieved by red blood cells or erythrocytes. These are tiny cells present in very high amounts in the blood that contain a protein called hemoglobin. This protein has a center with iron which captures oxygen molecules in the lungs and transports it to other tissues, where oxygen is released.

Figure 1- Illustration for red blood cells or erythrocytes. These cells without nucleus, contain inside a protein- Hemoglobin- that transports oxygen from lungs to the rest of the body. Hemoglobin contains iron, among other components. The iron is what confers these cells the color red and binds to oxygen molecules.

Artificial hemoglobin-based oxygen carriers (HBOCs) can potentially be injected in patients who have been through an accident in places where fresh blood is difficult to obtain, such as rural areas or war zones. Yet, the products tested so far contain only a hemoglobin-like molecule that could travel free through tissues and vessels and was not coated by a cell membrane as usually happens in red blood cells. Although it can provide a fast solution to stabilize patients, these strategies often produce cardiac and vascular toxic effects, such hypertension. For instance, given that hemoglobin is not surrounded by a membrane, oxygen changes occur very rapidly, which can cause cell oxidation in multiple organs (the same mechanism that makes apples and bananas brown after contact with air). These toxic effects are also dependent on another molecule – Nitric Oxide. This molecule is usually produced by the blood vessels to allow their expansion and increase blood flow (for instance during exercise this occurs in the blood vessels near the muscles). However, Nitric Oxide also binds to hemoglobin. When using HBOCs, the arrest of Nitric Oxide is faster than with red blood cells, causing the blood vessels to contract and causing hypertension. Therefore, a membrane that slows down these reactions could prevent the toxic effects of HBOCs. 

Figure 2- Oxygen and nitric oxide (NO) dynamics in blood vessels. NO is released by cells that cover the blood vessels, expanding these and increasing blood flow. Red blood cells in the blood release the oxygen molecules and arrest NO, reducing the NO amount and causing the contraction of the blood vessels. When surrounded by a membrane (red blood cells or artificial red blood cells), these changes occur slowly. In common hemoglobin oxygen carriers (HBOCs), hemoglobin is free causing the rapid release of oxygen and arrest of NO, which can have toxic side effects, as oxidation and fast compression of the blood vessels and possible hypertension.

Artificial red blood cells could then offer an improved strategy for these patients. In this case, the hemoglobin protein is surrounded by a lipid (the scientific name for fat molecules) membrane, like in red blood cells, preventing the toxic effects.  Additionally, these artificial cells also have a much longer shelf life (~2 years) compared with natural red blood cells (~42 days) and are compatible with all blood types. ​​Developed by a research team at the University of Maryland (UMD) School of Medicine, “ErythroMer” is made with human hemoglobin obtained from donated red blood cells that past their shelf life and is currently under preclinical testing. Although this product is currently dependent on hemoglobin from donated blood, the research team is developing a method to produce hemoglobin in the laboratory. This will increase “ErythroMer” availability. 

In the future, artificial red blood cells can offer an unlimited blood substitute for patients in critical state and may open the way for other artificial cell products. 

For more information:

https://www.science.org/content/article/ultimate-blood-substitute-us-military-betting-46-million#

https://kalocyte.com/

 

2024-10-28

This entry was posted in

Cell Biology

Comments

0 Comments Leave a comment

Under scrutiny: how spaceflight affects civilian astronauts’ health

On 16 September 2021, the first human spaceflight with an entirely civilian crew, Inspiration4, was launched into low Earth orbit from the Kennedy Space Center. The mission ended three days later, on 18 September 2021, giving the crew a chance to experience similar conditions to those on the International Space Station (ISS). This included exposure to ionising radiation, living in a vacuum and the challenges of a closed, hostile environment, along with isolation and limited Earth resources. However, it also presented scientists with a remarkable opportunity to conduct research on the biological and behavioral responses of non-professional astronauts during the early phases of spaceflight. The ambitious goal was to gather biological and cognitive data to create a comprehensive database that could inform future crew selection and mission planning.

At this point, you might wonder why we do not possess this data, given that we have been sending people to space since the early 1960s. The truth is, while we have a wealth of knowledge regarding the effects of living in space on the human body, much of this information comes from studies involving professional astronauts – individuals who have been rigorously selected and trained for years to cope with the unique challenges of space travel. If you are curious about life in space, the fearless Mary Roach (https://www.goodreads.com/book/show/9542311-packing-for-mars) answers all the questions you have ever wanted to ask but might have been to shy or embarrassed to say out loud. Wondering how to handle basic (and maybe not-so-basic) physiological needs in microgravity? You will find your answers there. Trust me, once you read it, you will be ready to start saving for a ticket on one of those zero-gravity commercial flights, just for the experience. It is highly recommended for everyone, especially aerospace enthusiasts.

With the advent of space tourism in 2001, our focus shifted towards civilians. Although the sample size was very small—only four crew members—this group was already well-gender balanced, comprising two females and two males. They were equipped with novel flight technologies, such as handheld ultrasound imaging devices and Apple Watches (yes, you read that correctly!). While the original article does not specify whether the crew members were allowed to keep their watches after the spaceflight study, they also employed new protocols for analysing gene and protein expression, as well as cellular and immune system function.

As expected, the three-day stay in the void induced a broad spectrum of physiological and stress responses, evident in changes to gene and protein expression and immune system function, alongside space motion sickness. Notably, cognitive ability remained largely unaffected. Interestingly, most examined factors did not differ from the pre-flight state upon their return to Earth, leading scientists to conclude that a short-term stay in space does not pose any major health risks. What is even more intriguing – yet perhaps expected – is the reported increase in happiness and decrease in boredom among the civilian astronauts during their flight compared to their pre-flight state.

Given the small sample size, all the collected data are very preliminary. However, as more civilians venture into space, we will gather additional insights into the physiological and cognitive responses of non-professional astronauts to life in space. Fingers crossed for all future space tourists! Let’s hope that one day, some of us will have the extraordinary opportunity to witness 16 sunsets and sunrises in a single Earth day while floating among the stars.

References:

1. Jones, C.W., Overbey, E.G., Lacombe, J., Ecker, A.J., Meydan, C., Ryon, K., Tierney, B., Damle, N., MacKay, M., Afshin, E.E., et al. (2024). Molecular and physiological changes in the SpaceX Inspiration4 civilian crew. Nature 632, 1155-1164. 10.1038/s41586-024-07648-x.

2. Overbey, E.G., Kim, J., Tierney, B.T., Park, J., Houerbi, N., Lucaci, A.G., Garcia Medina, S., Damle, N., Najjar, D., Grigorev, K., et al. (2024). The Space Omics and Medical Atlas (SOMA) and international astronaut biobank. Nature 632, 1145-1154. 10.1038/s41586-024-07639-y.

This entry was posted in

Stem Cells

Comments

1 Comment Leave a comment

What If a Cell Was a City #2 – Energy and Trash

It’s been almost a year since we (re)launched Science as We Know It. Our first post was a small imagination exercise where we pretended a cell was a city and drew some metaphors about what each cell organelle might be comparable to. You can (re)read all about it here.

At the time, some additional interesting parallels were worth exploring. However, in the interest of length, we kept them archived… Until now.

Welcome to What If a Cell Was a City #2 – Energy and Trash. This sounds exactly like the title of a movie sequel, doesn’t it? Well, movie sequels tend to be worse than the originals. So, let’s see how this one goes.

Mitochondria The Powerhouse Of The Cell

We are aware that calling the mitochondria the powerhouse of the cell is such a cliché. But, given that this comparison is used so many times, do people actually know why it is so?

To produce energy we need to eat food. Us, other animals and even smaller organisms. But the energy that exists in food cannot be used directly by our bodies. Proteins, fats, carbohydrates… All these nutrients come down to one single type of energy, a kind of energy “currency” called ATP: adenosine triphosphate (bless you).

The “industrial” process that takes place in the mitochondria can be resumed relatively simply: glucose (from food) + oxygen (that we breathe in) = carbon dioxide, water (that we breathe out) and energy (in the form of ATP).

ATP is then, just like electricity produced in a city’s power plant, used throughout the cell for any activities. 

Muscle cells need to move? ->  ATP!

Heart needs to beat? -> ATP!

Sperm cells need to wave their little tails to swim until the egg? -> ATP!

Chloroplast – The Greenhouse

If the mitochondria are the pollutant coal power plant, the chloroplast is the environmentally friendly renewable energy power plant, with (almost) zero carbon footprint. However, it does not exist in every cell. Animals, for instance, are not lucky enough to have one. Mostly plants and algae do.

The chloroplast is the place where photosynthesis happens. It is green because of chlorophyll, the pigment that is key to “absorb” the energy from the sun which is then used to make “food”.

The energy coming from sunlight is converted into energy (yes, our boy ATP!) which is then, together with captured carbon dioxide, turned into carbohydrates and oxygen. That’s the reason why plants are so important: they release oxygen and produce carbohydrates!

And, if you ever worried about your diet, you are probably aware that carbohydrates mean sugars. And if you ever have breathed in your life, you are aware that oxygen is good. Food and oxygen! Plants produce food and oxygen!

Too bad chloroplasts only exist in plant cells and algae, though. If we had them, we wouldn’t have to worry so much about actually eating. On the other hand, it is quite sad… Don’t you think plants are missing out on such amazing things as steak… Tropical fruits… Chocolate…?

Lysosome – Recycling Centers

A side effect of the industry and activity in any city is, of course, trash production. Whatever things we use and stuff we do, there will always be waste materials that we need to get rid off. And the same happens inside our cells.

Lysosomes are vesicles that incorporate complex molecules that are not needed in our cells. Inside lysosomes, the pH is low (so it is acidic) which helps with, together with other enzymes, the degradation of the molecules inside. Similar to what happens in the stomach, these contents are degraded inside this kind of waste-disposal center. 

And then, since our cells run on a sustainable economy, many of the products resulting from this digestion are brought back to the cell to be used to synthesize other components. Our cells might be a confusing city, but they for sure are environmentally friendly.

And here it is, after having a look at how the industry of protein production happens in our cells last year, we showed you today how our cells produce energy and recycle waste materials. 

If I were you, I’d stick around for one more year. Who knows what metaphors we will think about next year!

This entry was posted in

Stem Cells

Comments

0 Comments Leave a comment

Why future dads should care about their diet: it impacts your son’s health

Those trying to conceive are often aware of the importance of a healthy lifestyle for the quality of their reproductive cells and, ultimately, the health of their future children. However, a future father’s diet, in particular, can have a significant impact. Recent research has shown that what prospective fathers eat can influence RNA (ribonucleic acid) in their sperm cells, potentially affecting embryo development and increasing the risk of metabolic diseases that their children may develop later in life.

Let’s take a few steps back. DNA (deoxyribonucleic acid) is the hereditary material in nearly all organisms, including humans. While nuclear DNA is inherited from both parents, the DNA found in organelles called mitochondria is exclusively inherited from mothers. Maintaining the integrity of genetic information is crucial, and this is where various types of RNA come into play. RNA has several functions, including carrying genetic information from DNA to proteins and regulating gene expression. Although RNA is not inherited like DNA, it can still transmit information and influence how a new organism develops.

In both mice and humans, spermatogenesis is a two-step process. First, sperm is produced in the testes, and then it travels to an elongated organ called the epididymis, where it matures. Scientists have discovered that feeding mice a high-fat diet makes the sperm cells in the epididymis particularly sensitive to these dietary changes. While they did not observe any effects on sperm development or reproductive fitness, they did find that male offspring of these mice had increased glucose intolerance compared to those of control mice. Interestingly, when the mice were returned to a regular diet for a period long enough to allow the development of new sperm cells, the negative effects were fully reversible.

The sensors of the high-fat diet are a type of RNA called small non-coding RNA (sncRNAs) encoded by mitochondrial genome. These RNAs are delivered from the sperm to the egg during fertilization and may regulate genes involved in mitochondrial energy metabolism. This makes them a potential candidate for predicting how a father’s lifestyle may affect the metabolic health of his children.

So, future dads, it does matter what you eat—for your health and your sons’. Think twice before taking that next bite of deep-fried food. The good news is that for those willing to change their eating habits, the negative effects of poor diet on their offsprings’ health can be reversed.

References:

Tomar, A., Gomez-Velazquez, M., Gerlini, R., Comas-Armangue, G., Makharadze, L., Kolbe, T., Boersma, A., Dahlhoff, M., Burgstaller, J.P., Lassi, M., et al. (2024). Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs. Nature 630, 720-727. 10.1038/s41586-024-07472-3.

This entry was posted in

Stem Cells

Comments

2 Comments Leave a comment

Insulin – A Sweet Discovery

Today’s post is gonna have a sweet flavor. Because 103 years ago, on July 27th, a huge step in the treatment of diabetes was taken: the discovery of insulin. Using insulin is part of the daily life of many people who suffer from diabetes. But what really is insulin? And how does it play such an important role in treating diabetes?

Diabetes has been a known disease for thousands of years. It is known to be related to elevated levels of sugar in the blood. Historically, it has been documented as “honey urine” (a weird combination of words, I know). Diabetes patients’ urine was known to attract ants, due to their increased sugar levels.

Until not very long ago, the only way to deal with it involved changes in diet: reducing the consumption of sugars and carbohydrates. But, in 1921, Canadian scientists Frederick Banting and Charles Best discovered that insulin injections treated diabetes symptoms.

This discovery was so successful that, the year after, a 14-year-old boy became the first person to be treated for diabetes with insulin injection.

But what really is insulin and how is it related to diabetes?

So, let’s start from the beginning: When we eat or drink, glucose is absorbed into the bloodstream during digestion. However, for it to be used to produce energy, it needs to go into our cells, so that they can process it.

Insulin is a hormone that, under normal conditions, is produced in the pancreas. Its role is to precisely regulate glucose (sugar) levels in the blood, by mediating its intake into the cells. 

It acts as a kind of switch that allows the transporters that exist on the surface of our cells to open and allow glucose to move inside.

Without insulin, however, glucose will be floating around in the blood, never reaching our cells because its “doors” will never open.

In cases like this, when the pancreas does not produce enough insulin (or, in some other cases, the body is not able to successfully use the insulin), we have a case of diabetes.

Some of the biggest issues regarding diabetes have to do with the elevated levels of glucose in the blood. This accumulated build-up of sugar, over time, may lead to serious damage in the kidneys, the nerves (which can lead to typical diabetes problems in the feet), the eyes, in the heart… which can ultimately result in death.

And this is why the injection of insulin is so important in diabetes. In the absence of our own insulin produced by our pancreas, the injection of external insulin (which has had different origins: from isolation from other animals’ pancreas to mass production by bacteria) bypasses that problem, therefore opening the glucose transporters on the surface of our cells, allowing the sugar in our blood to reach its due destination and not stay around causing life-threatening troubles.

It is however important to mention that, although it can have genetic origins, diabetes can be prevented by practicing exercise, maintaining a good diet, and having a healthy lifestyle. You can extend your knowledge and read more about diabetes here.

This entry was posted in

Stem Cells

Comments

3 Comments Leave a comment

Police academy: An immune-cancer assignment  

In 2020 the world stopped due to an outbreak of COVID19. Around the world, journalists and scientists tried to break scientific expressions, such as virus, vaccines, and immune system, into simple ideas that everyone could grasp. People worldwide may now recognize the immune system as our body’s police force, that exists to fight invaders, as a virus. However, this immune-police force can help to fight not only outside invaders but also inside intruders, such as cancer. 

But how? 

In a very similar way by which the immune system identifies a virus, through antigens. These are proteins that are usually not present in our body so are seen as external invaders. Do you remember listening about the spike proteins in the news during COVID19? That’s it, a protein that was present in COVID19 virus and we used it as a base to produce vaccines, because it is seen by our immune system as an antigen, activating our police forces to fight COVID19. 

Now the tricky part is, cancer cells, despite coming from healthy cells that we have in our bodies can also have proteins that we usually do not have, for instance, cancer cells can modify the proteins they produce (we have a really cool post explaining how cells produce proteins- What If a Cell Was a city? – The Industry of Protein Production). Thus, cancer cells have antigens that can activate the immune system against cancer, like traces that our police forces can follow to find the invader. 

So why do we have cancer?  

Although our immune defenses can kill cancer cells in the beginning of their conversion to the criminal side, often cancer cells act like true crime experts and learn ways to widen their antigen traces, becoming invisible to our immune-police forces and growing their gang. Here it’s where scientists come with their police academy to train more and better police agents.

In this academy, immune cells get better at recognizing and killing cancer cells, therefore, they can be used as treatment. To this we call: Cancer Immunotherapy. Despite just being in clinical use since the 2000s, immunotherapy is already considered the 4th pillar of cancer treatment along with surgery, chemo- and radiotherapy. 

To accomplish this, in the past years, keen scientists have created multiple police tools and trained several police agents. This is the example of the most famous agent of our immune system- T cells

These are police agents that kill cancer cells once they recognize them by their antigens. Although efficient, for T cells to see cancer cells, the antigens need to be shown by specific molecules called- Major Histocompatibility complex (MHC). These MHC molecules are often decreased in cancer cells, making cancer invisible to T cells. To overcome this, T cells can be changed in the laboratory to identify cancer antigens that are not shown in these MHC molecules. To this we call CAR-T cells

Additionally, cancer cells can also armor themselves with weapons that impede T cells to kill them. For this, scientists create an antidote- proteins that cover those weapons, protecting the T cell agents and letting them do their work. This antidote has the name of immune checkpoints inhibitors (ICI), created by James P. Allison and Tasuku Honjo, which were awarded the Nobel Prize of Medicine 2018.  

Figure 1. Cancer Immunotherapy Strategies. T cells see cancer cells by antigens shown at MHC molecules. Since cancer cells can decrease their MHC molecules, one strategy is to use CAR-T cells, which are T cell changed in laboratory to see antigens not in MHC molecules. Cancer cells can also increase molecules (immune checkpoints) that decrease T cell killing activity.To protect T cell activity, immune checkpoint inhibitors (ICI) were created.


Many other agents are being trained in this police academy, including forensic agents (dendritic cells) whose expertise is to look for antigens and show them to T cells. Improving this police academy training is a key mission, as cancer cells can change their modus operandi. Despite the challenges, scientists around the world work every day in this mission with the belief that justice will prevail.

 

2024-06-28

This entry was posted in

Immune System Nobel Prizes

Comments

0 Comments Leave a comment

Blood – It’s as easy as AB(O)C

Today, on the 14th of June, is World Blood Donor Day. It has been promoted by the World Health Organization (WHO) over the last 20 years to highlight the importance of blood availability in healthcare and to celebrate voluntary blood donations worldwide.

When we think about blood, there is so much we could write about. From the cells that compose the blood, to how blood donations can save lives. We could even try to talk about vampires (that would be a fun challenge to address on a science blog…). 

But today we will focus on something related to the history of this date. The day of June 14th was chosen as an homage to the birthday of the Nobel laureate Karl Landsteiner. And if the name is unfamiliar, don’t worry, because I’m about to tell you WHO he was (see what I did here?).

Blood transfusions date back to the 19th century. The concept of solving big blood losses with the injection of blood donated by other people sounded, at first sight, like a not-very-complex idea, right? Blood is lost -> Blood is replaced -> Problem solved.

Well… No.

At this time, many of the transfusions ended up in death. It had such a low probability of success, that it was highly avoided or even rejected by most doctors. 

But why did this happen?

This is where Karl Landsteiner’s work came in. The fact was that when blood from different people was mixed, the red blood cells ended up clumping. In 1901, Landsteiner discovered that this was due to an immune reaction triggered when two bloods were mixed. A reaction that happens because the blood receiver has antibodies against the blood cells of the donor.

But not 100% of the time. Not with everyone. Why?

The answer is something you probably already heard about: Landsteiner identified the three blood groups A, B, and O. Blood transfusion between persons of the same blood group does not result in an immune reaction and, therefore, no adverse effects happen.

This is called the ABO blood group system: a person’s blood type depends on what kind of antigens (small molecules that can trigger an immune reaction) their red blood cells have on their surface. One can have only A antigens (type A), only B antigens (type B), both A and B antigens (type AB), or none at all (type O). 

However, a person does not necessarily need to only receive blood from the same blood type. Some blood types, despite being different, can be compatible.

This is due to the kind of antibodies that each person produces against the other blood types. A person with type A blood will produce and have in their blood antibodies against B antigens (the antigens that their blood cells do not have) and vice-versa. Therefore, a type A person cannot receive type B blood, and vice-versa. Otherwise, the antibodies they produce against the opposing blood type will trigger a reaction.

A person with type AB blood will not produce antibodies against either antigens A or B. This means an AB person can actually receive blood from every blood type (lucky bastards…). Even if the donor blood is just type A or type B, the AB person does not have antibodies against either of these, so no risk for any reaction.

What about type O? These are special cases. Their red blood cells have no type A or type B antigen. But their immune system produces antibodies against both antigens. This means that if they receive blood from any other blood type (A, B, or AB), they will have an immune reaction. This makes it so that type O people can only receive blood from other type O people (poor guys…). On the other hand, they can donate blood to any other person, because their red blood cells have no antigens at all, and therefore will cause no adverse reaction in any other person whether they have antibodies against A or B or both. They are so-called universal donors! But they cannot receive blood from any other blood group… (Evolution can be a real bitc… piece of work sometimes.)

Landsteiner performed a pioneering discovery and allowed for blood transfusions to go from a completely avoidable procedure to one of the most common interventions, saving countless lives.

Since then, other blood types have also been described (red blood cells can have other antigens besides A and B that can make them more or less compatible between them). For instance, the AB categorization is usually followed by a + or -, related to another antigen system, which is also very important to take into account when planning transfusions. 

Although blood transfusions can save lives, blood donations are constantly needed. That is exactly what is celebrated on this World Blood Donor Day. 

So, if you can, remember to give blood.
And happy blood donor day!

This entry was posted in

Immune System Nobel Prizes

Comments

2 Comments Leave a comment

Laugh is the best medicine: but why?

Dear reader, I will ask you for a moment of reflection: Have you ever had one of these moments of stress that you just wanted to release a very loud “AHHHHHH…” or one of those that you are crying all the water you have available in your body and suddenly someone or something makes you laugh?

While I hope this is not the case right now and you are not putting all your hopes on me to make you giggle, I want you to think how you felt after that laugh? Probably better, like a sudden medicine to your pain had been administered.

Well, that is because laughing is a very good medicine and yesterday, 5th May, was the International Day of Laugh, made to remember that sometimes the only thing we need to calm down our minds is not a 30-minute speech, nor a chocolate or buckets of ice cream, much less a pill, but surprisingly, just a good genuine laugh.

But why does this happen?

Although the reason for this relief can come in multiple ways, including at the psychological level, let’s go deep on what happens in our bodies and brain (despite the importance of psychology, I am still a biologist, so I will avoid a tough adventure in the lands of Sigmund Freud).

To answer this biological question, several studies have been done, mainly by showing the study participants videos with humour content followed by blood sampling or PET*. Yes, you can contribute to science while watching YouTube videos of mischievous cats and dramatic huskies, or while scrolling Instagram watching reels of Italians reacting to people breaking spaghetti.

These studies showed that at a biological level, laughter decreases the levels of DOPAC, which is a molecule present in the blood and that results from the destruction of dopamine (a very important molecule for our brains to feel pleasure and motivation). Therefore, the low levels of DOPAC indicate that dopamine is not being destroyed as before laughing, and we can store it in our brains, making us feel good.  

Additionally, cortisol was also reduced. This is a hormone released during physiological stress (including some diseases) and psychological stress and has multiple effects on our bodies, including the way we process sugars and accumulate fat (unfortunately I couldn’t find evidence that laughter makes us slimmer).

Lastly, laughter triggers a higher release of endogenous opioids (yes, our bodies can produce opioids). If you are asking, the reason why they are called opioids is because they activate the same type of receptors (other molecules usually present at the cell surface that can trigger multiple responses inside the cell) as opium. These can include the now famous endorphins (also released after practising sports) which are molecules mainly produced in our brains but have functions in our entire body, including slowing our respiratory rate and digestive system, explaining why we feel our bodies calming down after laughing.

Chemical mechanisms happening before and after laugh in the brain.

Though these biological changes can explain why laughing is sometimes indeed the best remedy, a lot of research is still needed to completely unveil the biological effects of laughing, which can be depended on the type of laugh (spontaneous laughter, conversational laughter, inducible laugh- the one you get after some beers and everything is funny etc…).

While more efforts are being made to understand whether laughter can be used as therapy not only for mental disorders but physiological diseases, one thing we know for sure: laughter is an excellent communication tool to integrate us within society and makes us more relaxed and happier.

So, my dear reader, whether you are a fellow scientist whose experiment has just failed, a parent of a stubborn child or pet that does not follow your rules, a broken heart soul or if life is just not being easy, go ahead and surround yourself with people that will make you laugh. 

Happy International Laugh Day!

PET: Medical imaging technology that allows to detect and locate certain molecules, such as dopamine or others, in organs.

References:

  1. Lee S. Berk et al. The American Journal of the Medical Sciences,1989
  2. Sandra Manninen et al., The Journal of Neurosciences, 2017
  3. Caroline Kaercher Kramer et al., Plos One, 2023

Cover art by Inês Caiado, inspired by an image generated using Microsoft Bing Image Creator, powered by DALL-E

2024-05-06

This entry was posted in

Stem Cells

Comments

3 Comments Leave a comment

DNA – The Four Letters of Life: A, T, C and G

Last week, on the 25th of April, the commemoration of the DNA Day took place. Celebrated on this day, the date when, in 1953, Rosalind Franklin, James Watson, Francis Crick, Maurice Wilkins, and their collaborators published their studies about the structure of – you guessed it – DNA.

In line with this, and given that we previously talked about the different structures found in a cell, we thought it would be a great opportunity to talk more about this amazing molecule containing pretty much all our information. (Yes, even more than your Instagram page.)

DNA stands for DeoxyriboNucleic Acid (bless you!), and it is famously shaped like a double helix of two strands that revolve around each other. Within this twisted ladder-like structure, you can find the information for the functioning, development, and reproduction of every known live organism.

How so?” you ask.

Well, if you think that the four letters that form life are L, I, F, and E, you are mistaken. They are actually A, T, G, and C. And no, I am not having a stroke. Here’s the thing, these long strands of the DNA molecule (a polymer) are composed of smaller pieces (monomers). These smaller molecules are called nucleotides, and there are four of them: adenine [A], thymine [T], guanine [G], and cytosine [C]. 

The sequence of these nucleotides is in itself a real code for the production of proteins, the biomolecules that constitute pretty much everything in a cell. So, each sequence of 3 nucleotides means a specific part of a protein, called an aminoacid: ATT means one aminoacid, GAC means another, and so on… You basically have a library of all the proteins your cells can produce being encoded in this 4-letter alphabet!

Thanks to its double-helix coil shape, it can turn around and around on itself so it can take up the least amount of space possible. To give you an idea, if we completely stretched out the DNA of one single individual human cell, it would measure approximately 2 meters. But the nucleus of the cell, where it is contained, only measures about 6 micrometers in diameter. (If you think Marie Kondo was the master of space optimization and organization, think twice!)

The smart thing about it is that the important parts of the long DNA molecule are specifically uncoiled, according to the needs. If a region of DNA is needed to be “read” for a specific protein, it unfolds and opens up that area in particular. And then it “closes again” when not needed anymore. These very long fibers of DNA, when condensed and packaged, form the chromosomes. Which, precisely when they are so packed, can be easily visualized under a light microscope. 

DNA is not only very efficient for information storing but also for information proliferation. When preparing for cell division, the entirety of DNA is replicated: the helix shape uncoils, both strands separate and new nucleotide building blocks come to “copy” each one of the strands, generating two. These will then form two sets of chromosomes, which can be split between the two new cells that form after division.

And here it is. Now you know why the forensics TV shows enjoy DNA so much. It is a biological trace that is different for every human that exists or ever existed. And all of this is encoded in only 4 letters.

So, hopefully, this article made you think twice before committing a crime.

Happy DNA day!

This entry was posted in

Stem Cells

Comments

2 Comments Leave a comment

How to lose a tail in 25 million years

Coccydynia, also known as tailbone pain, is perhaps the rare moment when we are actually aware of the presence of our vestigial tail. But let’s delve deeper. Imagine the convenience of living with a tail.* Both hands are occupied and you need to grasp something else? Just take a cue from the opossum with its prehensile tail adept at grabbing branches – it seems so effortless. If only it were not for an event that transpired around 25 million years ago, we might have been sipping our favourite drink while wielding cutlery in both hands. Instead, evolutionary pressure compelled us to abandon the arboreal lifestyle and adapt to a new style of locomotion. So, time to go back in time to unravel the genetic basis of tail-loss with researchers from New York University.

Without a time machine, teams led by Jef Boeke and Itai Yanai had to begin their detective work somewhere. Comparing sequences of genes predicted to be involved in tail-loss between two evolutionary closest animal lineages – one with tails and the other without, sounded like a reasonable starting point. Among these relatives were hominoids, encompassing humans and apes, thought to have lost their tails around 25 million years ago. This pivotal moment coincided with their divergence from their evolutionary siblings, ancient Old World monkeys, whose tailed family members include baboons, macaques, and mandrills. As genes involved in the loss of shortening of the tail were previously selected, scientists could narrow down their search to these specific genome parts of hominoids and Old World monkeys.

Genes are composed of coding segments known as exons and non-coding parts called introns. Despite being labelled as ‘non-coding’, these sequences are integral to a process called alternative splicing, where introns are removed from mRNA (messenger molecule carrying gene sequence). This process is incredibly powerful, as it can lead to rearrangements of various exons. Consequently, these mRNAs can be translated into different forms, known as isoforms, of a protein, that will eventually serve diverse functions within a cell.

Upon closer investigation of gene sequences associated with the absence of a tail or its reduced forms, scientists made a significant discovery. They found an insertion within one of the introns of the hominoid TBXT gene. This inserted sequence to a type of Alu element, known as a transposable element or transposon. Transposons, also dubbed as ‘jumping genes’ or ‘tiny genome travellers’ are relics of an ancient virus infection. They populate up to 50% of our genome and their selfish goal is to replicate themselves. Hence, they jump around and insert in different regions of host genomes, sometimes disrupting genes in the process.** In this case, an insertion of the Alu element occurred around the same time when hominoids lost their tails. Moreover, it happened in a gene crucial for tail development. After a series of few elegant experiments later, researchers uncovered the mechanistic explanation of what transpired, leading to the birth of mice without tails.

The inserted Alu element interacts with the different Alu element that has been present before in the next intron. Together, they form a loop, causing an exon located between these two elements to be excised during alternative splicing. This results in the production of a shorter isoform of TBXT mRNA. However, merely generating a slightly shorter TBXT isoform is not sufficient to cause tail loss. Tail-less mice are only born in cases where there is either a lack of full-length TBXT or a significantly higher proportion of the shorter isoform.

Proposed mechanism of tail loss

As science is an endless journey of discovery, every result leads to new questions. This time was no different. Some of the mice without tails also exhibited defects in neural tube closure, a condition similar to the spina bifida in humans. While it may not be surprising given the importance of the TBXT gene during embryo development, it raises the question: Why would evolution deprive us of tails but leave us with the (rare) risk of developing serious health conditions?

* It is worth noting that animals also experience tail pain. Whether with or without a tail, life is not devoid of suffering.

** Rest easy knowing your cells have evolved mechanisms to curb the activity transposons.

References:

Xia, B., Zhang, W., Zhao, G., Zhang, X., Bai, J., Brosh, R., Wudzinska, A., Huang, E., Ashe, H., Ellis, G., et al. (2024). On the genetic basis of tail-loss evolution in humans and apes. Nature 626, 1042-1048. 10.1038/s41586-024-07095-8.

This entry was posted in

Evolution

Comments

0 Comments Leave a comment

Lake Malawi: A haven of biodiversity

Nestled between the countries of Malawi, Mozambique, and Tanzania, lies a long, thin, and deep Lake Malawi, also known as Lake Nyasa or Lago Niassa. Despite its status as a natural wonder, the shimmering waters of Lake Malawi serve a vital earthly function – sustaining the livelihoods of countless local fishermen and their families. For generations, these fishermen have practiced their craft on traditional wooden boats, using techniques passed down from their fathers and grandfathers. Little could they have imagined that their daily routines would play a crucial role in a scientific article.

What truly sets Lake Malawi apart is its astonishing biodiversity, harbouring around 15% of all freshwater fish species on Earth. Interestingly, the lake is a home to more than 800 species found only in this specific space (scientifically called “endemic”), all descending from a common ancestor that lived there 800 years ago. One might immediately assume their genomes are vastly different, but that’s a near shot. There is basically no difference. So where is the rub? That’s what caught the interest of a group of scientists from the UK. From awakened curiosity to experiments, just one step…

As we read in the “Methods” section of the original article “All cichlid specimens were bought dead from local fisherman…”. Armed with curiosity (and fish samples straight from Africa), scientists decided to unravel the mysteries of Lake Malawi’s inhabitants.

On the researchers’ table lay a diverse array of specimens, each representing a distinct ecological niche and dietary preferences. Among them were the livers and muscles of six different species: the pelagic piscivore, Rhamphochromis longiceps, the deep-water pelagic carnivore, Diplotaxodon limnothrissa, two rock-dwelling algae eaters, Maylandia zebra and Petrotilapia genalutea, the benthic invertebrate-eating sand and rock-dweller, Aulonocara stuartgranti, and the inhabitant of rivers and lake margins, Astatotilapia calliptera. Upon closer look at DNA, scientists pinpointed a potential culprit – DNA methylation. More just than a decorative motif, this reversible modification of DNA, when present at sites of transcription initiation, modulates expression of genes. Such methylation effectively turns off genes, making them no longer active inside a cell. The most prominent differences between investigated fish from Malawi Lake were observed in the methylations of liver-specific genes that encode proteins involved in metabolism of specific dietary components. Further investigation led scientists to discovery of another significant disparity, common across multiple tissues within one species. Researchers hypothesised that the lack of methylation in genes important for eye development, leading to larger eye size of Diplotaxodon limnothrissa,represents an evolutionary adaptation to life in the deepest, darkest depths of the lake. Altogether, this study highlights  DNA methylation as an evolutionary trick to adapt to various environments.

Having had the pleasure of listening to the leader of the above-mentioned group of scientists at a recent conference, I can attest to the fact that the pursuit of scientific discoveries frequently leads researchers to breathtaking locations to personally collect specimens. As readers, all we can do is eagerly await the fruits of their labour. So, stay tuned, there is surely much more to come from the depths of Lake Malawi.

References:

Vernaz, G., Malinsky, M., Svardal, H., Du, M., Tyers, A.M., Santos, M.E., Durbin, R., Genner, M.J., Turner, G.F., and Miska, E.A. (2021). Mapping epigenetic divergence in the massive radiation of Lake Malawi cichlid fishes. Nat Commun 12, 5870. 10.1038/s41467-021-26166-2.

This entry was posted in

Evolution

Comments

0 Comments Leave a comment

Older Posts