WISP

We take a lot of things for granted about human biology. Those are the “fundamental truths” we learned all the way in middle school. One such assumption is that a cell division results in the creation of 2 daughter cells. And, it does hold true for most cases. Things are different, however, once we venture into the realm of the pathological, where many generalizations break down. Out of the many ways mitosis can go wrong is when a defect of the mitotic spindle leads to a tri-, tetra-, pentapolar or higher order division. Toxins, infections and radiation are known causes for this phenomenon. Outside of these influences, multipolar mitoses occur primarily in cancer cells and early in embryonic development. How multipolar mitosis works No matter where it happens, if a cell divides into more than 2 new cells, the chromosomes cannot be distributed equally between the daughter cells. The resulting genomic instability favors further mutations, creating a vicious cycle that frequently ends in cancer. Oncogenic viruses such as HPV and HBV express proteins that disrupt the normal functioning of the mitotic spindle. Unsurprisingly, cells in lesions caused by HPV frequently show multipolar mitoses and aneuploidy. That is, an abnormal number of chromosomes.  Human zygotes cleave directly into 3 blastomeres (the products of the first embryonic divisions) with a surprisingly high frequency of 12.2% in vitro. Historically, during the early days of in vitro fertilization (IVF), anyone seeing those 3 cells would have assumed that one cell from the first division underwent its second division early. Subsequently, those non-viable embryos would have been implanted. Due to the low percentage of successful pregnancy for one IVF embryo, multiple embryos are implanted per pregnancy. This increases the risk of complications. Human assisted reproduction laboratories around the world are relying more and more on time-lapse monitoring of the zygotes. This allows us to select for the highest quality embryos, on multiple criteria. The challenges we face The drawback, however, is that exposure to light negatively affects the number of blastomeres and the ability of the embryo to insert itself into the uterine lining. For reference, the amount of light exposure during regular IVF amounts to 25 minutes, as opposed to ICSI (intracytoplasmic sperm injection), which is 50 minutes. Aside from this, we use preimplantation genetic diagnosis (PGD) to screen embryos for mutations, but this requires the removal of 1-2 blastomeres. In the case of mosaicism, mutations in the remaining blastomeres remain undetected. So this technique, though useful, has its limitations.  Shortly, the occurrence of multipolar mitoses is particularly noteworthy for its association with genomic instability and cancer development. Furthermore, the high frequency of tripolar divisions in human zygotes highlights the intricacies involved in early embryonic development and assisted reproductive technologies. Advancements such as time-lapse monitoring and preimplantation genetic diagnosis (PGD) have improved embryo selection and screening. However, they come with their own set of challenges. Understanding these phenomena underscores the ongoing need for research on cancer and assisted reproduction. If you found this article interesting and want to take part in shaping the future, stay tuned and stay curious with us! You can read the main article here; additional references here and here. See you next time. About the author…  Hello 🙂 My name is Matei and I am a second year medical student who loves science, video games and skiing. 

Breast cancer is the most frequent type of cancer in women. Even though mammography is an excellent screening tool, it may still not be enough for early detection of breast cancer. Could there be any other form of early identification? Scientists discovered that dissemination of cancerous cells starts at the very early stages. This means that they can be found in the blood. Taking advantage of this event, these cells’ DNA can be a tool for identifying breast cancer even a year prior to the manifestations that could be detected by the mammogram! A story about methylated DNA At first, they took samples of cancerous tissue and White Blood Cells (WBC) in order to extract DNA. Then, using Reduced Representation Bisulfite Sequencing (a method that cuts DNA into specific segments, then sequences it) together with PCR and methyltransferases (in order to maintain the methylation sequences) they found tumor-specific methylation patterns (18 to be exact). And one of them is the region called EFC#93. Methylated DNA has now entered the discourse. But what even is a methylation pattern? Our DNA has some regions called CpG islands – regions formed of cytosine followed by a guanine that repeats every few bases. A methyl radical can be attached to these C-G repeats, forming methylation patterns. EFC#93 contains 5 C-Gs. Some of these patterns are specific to cancer cells (the more methylated ones) and some are WBC specific (the less methylated). This is important, because in the bloodstream, the most cell-free DNA comes from WBC, and it is necessary to have a clear distinction between them.  The scientists then compared these results to DNA extracted from the serum of cancer patients and discovered a correlation between the presence of EFC#93 methylation pattern and the disease prognosis. If present, the prognosis is unfortunately worse. Furthermore if Circulating Tumor Cells (CTCs) are also present, the chances of survival become less and less favorable. But it is not just bad news! EFC#93 presence in seemingly healthy people could indicate a very early diagnosis of breast cancer, thus enabling earlier diagnosis and  treatment.  If you found this article interesting and want to take part in shaping the future, stay tuned and stay curious with us! Read the full text here. See ya’ later! About the author… Hi, my name’s Teodor, a second year medical student. I am a science enthusiast, amateur speedcuber, and hardcore metalhead.

Transplantation is a very helpful, yet ethically ambiguous practice. Despite its betterment of millions of lives worldwide, transplantation is an elusive treatment: only 10% of patients in need of a transplant actually receive it, according to the Global Observatory on Donation and Transplantation (GODT). The demand for transplants is steadily increasing, while the supply is limited and swiftly declining; this creates a surge in human trafficking with the purpose of unlawfully obtaining organs. In addition to that, whether or not you receive the treatment depends on a series of factors. Those include age, gender (with women being more likely to be living donors while men are the vast majority of recipients), socioeconomic status, ethnicity, place of residence, according to the European Public Health Alliance. What can be done to mend this disparity? One solution is growing humanised organs in animal embryos. Although growing mouse organs inside rat embryos was possible, the growth of human organs inside pigs was seen as unmanageable, until recently. Researchers have found a way to grow human embryo kidneys inside pig chimeras. That is, “an organism containing a mixture of genetically different tissues, formed by processes such as fusion of early embryos, grafting, or mutation”, according to Oxford Languages. This is an outstanding feat since pig cells and human cells have different physiological needs. Moreover, the pig cells compete with the human cells for resources, thus inhibiting the growth of the latter.  Innovation in genetic engineering  The way the researchers came over this issue truly is astounding. First, they genetically engineered a single-cell embryo that was missing the genes needed for kidney development. Thus, they created a space in which the human cells could grow uninhibited by the pig cells. Then, they engineered human pluripotent cells (cells that have the capacity to form any other cell type). They increased the cell’s ability to integrate into a different organism. At the same time this decreased its chances to self-destruct. The researchers grew the chimeras in an environment that provided the specific nutrients for both pig and human cells. Last but not least, they implanted the chimeras in the surrogate sows. After 25 to 28 days they terminated the gestation. The researchers found that after this period the embryos had structurally normal kidneys, in the mesonephros stage. The kidneys were composed of 50-60% human cells. They also assessed whether human cells migrated to neural or germinal tissues. It was found that the human cells were mostly localised in the kidneys. The next step is to let the embryos develop further and to assess the kidneys at every stage. However, it is still a long way before this study may be used clinically: the kidneys developed in the chimeras still have pig blood vessels, meaning they are not suitable for transplantation. Read the full text here. As always, if you found this study interesting, stay tuned and stay curious with us! About the author… Hello 🙂 My name is Ilinca and I am a third year medical student that dabbles in a little bit of everything. I have an undying thirst for knowledge and a great talent for procrastination. Oh and I love hairless cats with all my heart!

Did you know that tiny leaks in your brain’s blood vessels can lead to dementia and stroke?  These leaks are caused by damage to the supporting structure of the vessels. They are kind of like faulty pipes in your house. But scientists at Cambridge University have grown miniaturized versions of these vessels in a lab. As such, they’re using them to find ways to plug the leaks and prevent these devastating conditions. Imagine millions of tiny pipes delivering vital blood throughout your brain. That’s the job of small blood vessels. When these pipes get damaged and leaky, blood seeps out, harming brain tissue. This damage, called cerebral small vessel disease (SVD), is a major cause of both stroke and vascular dementia, affecting nearly half of all dementia cases worldwide. Dementia is a general term for a decline in thinking, memory, and reasoning skills that interferes with daily life. SVD disrupts the blood flow needed for healthy brain function, contributing to this decline. Searching for clues in the fight against dementia Until now, understanding SVD has been tricky. While some similarities exist, animal brains differ significantly from human brains. These differences are particularly pronounced in areas related to higher-order thinking and complex cognitive functions. This limits the usefulness of animal models in replicating the specific ways SVD disrupts blood flow in humans. That’s where the lab-grown blood vessels come in. These mini-vessels are created from reprogrammed skin cells of patients with SVD.  By studying these tiny replicas, scientists have discovered that the leaks are caused by damage to the scaffolding around the blood vessels.  This scaffolding, called the extracellular matrix, is crucial for keeping the vessels strong and leak-proof.  In SVD, the matrix breaks down, allowing blood to escape. The culprit behind this breakdown?  Molecules called metalloproteinases (MMPs).  Normally, MMPs help keep the scaffolding healthy, but when there are too many, they wreak havoc, like overzealous apprentices with too many brooms! The good news is that the scientists were able to stop the leaks by treating the lab-grown vessels with drugs that target MMPs.  While these specific drugs have side effects and aren’t suitable for treatment, they prove that targeting MMPs is a promising approach.  The scientists can now use their mini-vessels to test new drugs aimed at preventing these leaks and protecting our brains. This research offers a glimmer of hope for millions struggling with the effects of SVD.  By understanding the leaky pipes in the brain, we can develop treatments to keep blood flowing and our minds sharp. Read the full text here. Until next time, stay curious! About the author… Salutations, fellow enthusiasts! I’m Dumitrita, a history and board games aficionada with a fascination for butterflies. Oh, and whenever I feel sad I watch Quokka photos, 10/10 would recommend!

The Nobel Prize is the most prestigious award in science. Katalin Karikó, PhD and Drew Weissman, PhD had the great honor of receiving 2023’s prize in Medicine and Physiology for their work on modifying mRNA in order to resist the immune response. It led to the production of the COVID-19 vaccine, undoubtedly one of the most influential inventions of the last few years.  But what did the winners actually discover? Well, let’s dive into the wonderful molecular world of our bodies. We have a protein called PKR (RNA-dependent protein kinase), a soldier of our immune response. The researchers found that it does not efficiently bind RNA with modified bases. Here is how it works. Into the world of proteins PKR is a protein that inhibits translation of mRNA. PKR is activated by many kinds of foreign RNAs, be it double or single stranded, long or short (like those that could be found in RNA viruses). On the one hand, this protein is useful for our immune response. It is able to stop translation of mRNAs into foreign, maybe harmful proteins. On the other hand, it prevents the human body from receiving lab-made helpful mRNA. The laureates found that pseudouridine (Ψ) enriched mRNA is translated more efficiently than unmodified mRNA. They theorized that it may have something to do with PKR, so they started testing. At first, they transcribed some mRNAs in vitro, using modified nucleotides. Then they compared modified with unmodified mRNA. mRNA enriched with Ψ activated PKR less. Therefore its translation is less inhibited. However, when PKR was inactive/absent in the cell, there was no difference in the rate of translation of modified and unmodified mRNA. Moreover, they confirmed that modified mRNA is not a competitive inhibitor (it doesn’t bind well to PKR). This means that if there is a mixture of both types of foreign mRNAs, translation would still be inhibited. Even though there are some differences between in vitro and in vivo, it is needless to say that this paper had pioneered a new way of treating pathologies. We now managed to get our bodies to produce proteins that we want quickly and without the scare of genetic alterations.  If you found this article interesting and want to take part in shaping the future, stay tuned and stay curious with us! You can find the full article here. See ya’ later! About the author… Hi, my name’s Teodor, a second year medical student. I am a science enthusiast, amateur speedcuber, hardcore metalhead, and dedicated weeb.