What a rollercoaster ride!

by Kayla Lesch

In 2021, I completed my BSc degree in Biotechnology at the University of the Western Cape with a Magna Cum Laude and did exceptionally well in all my modules. Although everything was online due to COVID-19 including lectures and exams, it was still tough. Somehow, 2021 was one of my greatest academic years. This was probably due to me working at my own pace and having discipline. It all paid off, as it landed me quite a few jobs and most importantly my acceptance for honours at the University of Cape Town. 

My honours year (2022) has been anything but easy. However, I’m thankful that I’ve been given this opportunity. I’m proud to say that I’m one of four students in the BMedSci (Hons) Biomedical Forensic Science, Department of Pathology, Division of Forensic Medicine and Toxicology. 

Throughout the year, I never thought I was capable of being an honours student. At the beginning of the year, I wanted to drop out, but something told me not to give up. The toughest part was initially the overall workload. I experienced plenty emotions and had a lot of ups and downs with my academics. During this year, the BMedSci honours students done coursework (lectures, tests and exams), assignments, and project-related work simultaneously. We had presentations and assignments due straight after one another. I was afraid that I could never meet any of the deadlines, yet I did! 

Honours was a massive leap from my undergraduate degree. Mainly since my two years out of the three-year undergraduate degree was online-based and this included exams. This year was the first year since 2019 that I wrote in-person exams, and it was tough! I forgot entirely how to study word for word and retain information. However, somehow, I managed to write each exam and it wasn’t as bad as I thought it would be. To my surprise, I happened to get extremely good marks in all my modules.

This opportunity has also allowed me to meet amazing and educated people! The individuals within my honours programme overall were very friendly and helpful. Each individual within my division was extremely welcoming and supportive. Everyone was willing to share their experiences and knowledge. I appreciated how each of them also gave their advice on ways to cope, handle stress, calm the nerves and mentioned tips for growth in the specific Forensic Science field.  I would’ve never thought that my classmates, would now be a few of my closest friends. Honestly, without these people, I don’t think I would’ve been able to cope with this year as well as I am. 

Honours has coached me to be independent and take initiative. It has shown me that it’s okay to make mistakes but learn from them, and that you’re definitely not the smartest in the room! It has taught me that hard work pays off and to always do the that best you can, as your best is enough. It has taught me that I am capable and educated and lastly, it has shown me how strong I am. Honours has also taught me a lot about the research sector and how important research is overall. It helped me focus solely on my education and my goals, and in some strange way, it helped me evolve. Honours improved my reading, writing, my critical analysis, and so much more. I was told by many, that honours are one of the worst years in post-graduate studies, and according to my knowledge I must agree. Even though being in honours is a tiring, bitter-sweet journey, I can honestly say it is worth all the stress! 

Forensic Science has always fascinated me since I was young! I loved the fact that the individuals involved aimed to solve cases for justice. I loved that they aimed to serve and help others. Honours in Biomedical Forensic Science made me even more intrigued, experiencing first-hand how the field of Forensic Science works in South Africa! Surprisingly Forensic Science is way more complicated and diverse than the CSI TV shows we grew up watching. Did you know, Forensic Science consists of science, law, and medical aspects!? It makes me feel so important, to be involved with real-life cases and learn all the things that’s needed as a forensic scientist. In the beginning, we learnt the different disciplines within forensic science which included Entomology, Medico-legal Death Investigations, Genetics and lastly Toxicology which is what my honours project titled “Retrospective Analysis of Routine LC-QTOF/MS Toxicological Screening Results in Post-Mortem Casework” entails. I never knew forensic science was so diverse and that it had so much room for professional development. I cannot wait to one day contribute to this field and positively impact the lives of others.

Regardless of the rollercoaster of emotions I’ve been on during this year, experiencing both good and difficult times, I’m grateful. Without this experience, I wouldn’t have been this resilient and shaped into the woman I am today, and one day will be. I still have 6 weeks left of my honours year and I’m ready to face it head-on!

A student’s job is to learn, not know

by Imraan Dixon

There’s a cognitive bias called the Dunning-Kruger effect first described by two aptly named researchers, David Dunning and Justin Kruger (funny how things always line up like that, huh?). Essentially, it causes people with limited knowledge to overestimate the extent of that knowledge. Regardless of how true to life the Dunning-Kruger effect is, there is a popular interpretation of it that looks something like this:

When we’ve explored the tip of the knowledge iceberg, ignorant of what lies beneath, we assume we are more knowledgeable than we actually are. Once we are able to see into the depths and how far out of our reach it is, we realise that what we know is a but a droplet in the grand scheme of things.

Honours really gives us the freedom to search and learn about the topics we want to. Undergrad coaxed us with the gentle guide of lecture material. But Honours is conservative on that front, opting to encourage us to seek out knowledge autonomously, bounded only by our own eagerness and deadline constraints. It is through this that I’ve plummeted into the so-called “Valley of Despair”.

Aware of how little I really know, thoughts creep in. Thoughts that I’m not living up to the Honours standard. See, I wasn’t originally accepted into Honours. The only reason I made it here is because space opened up from other admittees leaving. Where does that put me amongst my peers? An off cut that was only put in the final product, because the packaging still had some free space in it…

You know what, though? That’s a bit self-centred, isn’t it? Tsk, tsk, tsk. Let’s not pretend that there aren’t people out there who feel like they are underperforming. I’m not saying there’s definitely people out there who feel like that – I speak only for me, myself, and I – but chances are that I’m not the only one with these insecurities. It makes sense, in a way. Students are integrated into labs where it’s likely that the majority of their interactions are with people on a higher level than them. They’re constantly exposed to Master’s and PhD students who are more experienced. In a way, perhaps those students start to be seen as peers regardless of the degree they hold.

What’s comforting for me to think about is that it’s okay to feel incompetent. It’s okay to feel like I don’t have it all or that I’m lacking knowledge that I assume is supposed to be basic. It’s okay if there’s some things that I can’t do with my current skillset. I’m a student. I’m not here to do. First and foremost, I’m here to learn. The practical aspect is there to facilitate this. The idea that, just because I’m a postgraduate, I’m supposed to be a full-fledged researcher swimming in grants and sleeping in sheets made up of hundreds of my published papers is absurd.

The takeaway, for me, is that I should be a lot more forgiving on myself for my gross inaptitude. Sure, I shouldn’t be complacent, but shooting myself in the foot by psychologically punishing myself like this will hamper my ability to walk forward. After all, I could very well be at the level of knowledge I’m expected to be at and I’m just looking at things through murky lens. Such a preposterous idea! But maybe I just need new glasses…

Learning experiences in 2022

by Caylin Mc Farlane

I realized I needed to pace myself when it comes to how much I put into my studies. People had told me Honours was going to be difficult, but this is much more difficult than what I expected.

The course I chose is Clinical Anatomy and we had our first techniques exams in March. Most of our learning was crammed into 2 months of intense studying and understanding of human anatomy. This would be the first time I had written a test in 5 years, so I had decided to give it my all, because I had wanted great marks. Yet, after the techniques exam was done, I felt I had failed. It felt as if all the hard work I had put into studying was for nought. I had to accept that I wasn’t cut out for academia or lower my expectations of myself.

With all the intense learning and studying for techniques, I had stopped taking care of my mental health. Therefore, I had a breakdown. I was burnt out and the year wasn’t finished. I didn’t realise how much I had put into getting great marks. Yes, I enjoyed myself, and yes, I received great marks, but the cost wasn’t worth it. I had to find a way to balance my studies and the other parts of my life, otherwise I wouldn’t survive 2022.

It’s been a few months since then and I’m getting better at finding the balance. Now, I’m working to achieve good marks. The lesson I learnt was to be realistic about my expectations regarding Honours and myself. Yes, Honours is difficult, intense and sometimes crazy, but that doesn’t mean I won’t enjoy Honours.

Mary Poppins (1964) said, “In every job that must be done, there is an element of fun. You find the fun and ‘snap’, the job’s a game.”

Finding the fun in writing this, was finding a way to incorporate the quote.

Goodluck to all the future Honours students. Remember to take care of your mental health and yourself.

I would be just fine, right?

by Gomolemo Molope

Hey, I am Gomolemo. A young individual from Gauteng who is aspiring to be a scientist. I cannot share a whole lot more about myself right now, but I will share something in particular. The final semester of my undergraduate studies was the most nerve-wracking time of my life. I would try to make the most of my days but my thoughts were always about doing well on my final exams, ultimately getting my degree and then furthering my studies. On top of that, I would check my email regularly to see if any of the universities I had applied to do my honours at had
accepted me.

Once the exam season had finally ended and the long-awaited festive season was approaching. I received an email confirming my admission to UCT. To say that I was happy would be an understatement. I was over the moon! I could not wait to share these amazing news with my family and friends. As excited as I was though, I realised that going to UCT would mean that I would have to move to a different province and stay in a place that was completely new to me. Extremely far from friends, family and home – my comfort zone. However, I will admit that in high school my friends and I would constantly say, “I can’t wait to leave high school. I will finally feel grown and independent.” Needless to say, that is every teenager’s dream. However, it started to feel like everything was suddenly happening way too fast and I felt like I was no longer ready to be grown and independent. On the other hand, I kept thinking that it really could not be all that bad. I would be just fine, right?

Soon after New Year’s Day, I finally made it to Cape Town. I was overwhelmed with a feeling of excitement and a dash of fear. But surely I would be just fine, right? A few days into my stay I eventually got to meet my stream convenor and
classmates for the first time. Surprisingly, many of my classmates were just like me, in that they had now moved to a place which was totally unfamiliar to them. It was during our orientation that we realised that the journey we were now embarking on would not be as terrifying as we had imagined. Although we had all just met, we discovered that together we would form the best support system for one another. Our similarities would be what allow us to form a strong bond which would make those days away from family and friends slightly bearable. Our connectedness would be the source of strength and courage needed to help us through the eventful year ahead of us.

It certainly did not take me months to finally believe that I would be just fine. All my uncertainties and fears were slowly overcome with each passing day. That was all thanks to my stream convenor, lecturers and most importantly my
classmates. A small group of compassionate and friendly people who somehow showed me that change is not always scary. They revealed that stepping out of your comfort zone allows you to live a fulfilling life in which you discover your
abilities and potential. You learn to stand on your own and experience moments that will allow you to grow as an individual. So with all that I have shared, trust me when I say that throwing yourself into the unknown seems daunting. But take that leap of faith because in the end, you will be just fine.

The Mystery Behind Neuronal Death in ALS

by Imraan Dixon

Imagine the things your body is capable of. Imagine even the little things like stretching, scratching that itch, talking, and eating. Now, imagine not being able to do any of that, each ability you’ve had for as long as you can remember slowly eroding away. Every little thing we may take for granted like being able to swallow, being able to speak, or just being able to move our bodies is a gift that a person with amyotrophic lateral sclerosis (ALS) soon loses.

ALS is a neurodegenerative disease characterised by the progressive death of motor neurons in the spine and the brain that control voluntary muscle movements. The death of these neurons leads to the subsequent death of muscle cells. The loss of motor neurons spreads to other parts of the body leading to the inability to move, eat and swallow, and speak. Eventually, this fatally leads to the muscle and nerve cells of the diaphragm – the most important muscle involved in breathing – also dying. Now, symptoms and disease progression may vary, but ultimately one’s life and loved ones are affected severely.

There is unfortunately no current cure for ALS. All that can be done right now is supportive care that can potentially increase life expectancy but at the cost of quality of life. The difficulty in finding effective long-term treatments is due to our lack of understanding of how this disease occurs. There are a multitude of genetic and environmental factors that play a role in ALS, so the picture is quite complex. One fundamental question underpinning ALS pathogenesis is:
“Why do those neurons die?”

Firstly, cell death is divided broadly into two categories. We have accidental cell death that is uncontrolled and typically caused by direct chemical or physical injury. Then, we have regulated cell death (RCD) that is controlled and regulated by our own cells. One major kind of RCD is “apoptosis” which is typically triggered by death ligands (molecules that signal cells to undergo RCD) and a caspase cascade (a chain reaction of caspase molecules that result in apoptosis). It
was originally thought that motor neuron death was caused by apoptosis, but inhibiting it did not protect neurons in ALS. Then, “necroptosis” was suggested as a mechanism. It’s another form of RCD that’s typically caspase-independent and driven by inflammation. However, if we get rid of MLKL – a critical component of necroptotic signalling – we find no changes in neuronal death.

A group of researchers in Australia aimed to find a mechanism underlying neuron death in ALS. That led them to “ferroptosis”. Ferroptosis is a relatively newer discovery and also a form of RCD that is iron-dependent and caspase-independent. Ferroptosis is typically caused by iron dysregulation and glutathione peroxidase 4 (GPX4) depletion that result in lipid peroxidation and cellular membrane damage (lipids are a major component of cell membranes). GPX4 is a major regulator of ferroptosis as it is acts as a defense against lipid peroxides, preventing widespread cellular damage. It does require glutathione (GSH), an antioxidant, in order to do so. See, as it turns out, accumulated iron, lipid peroxidation, and glutathione depletion were found in spinal cord and brain tissue of affected ALS individuals. See the link here?

To test if ferroptosis was indeed the cause of cell death in ALS, the researchers tested the effect of GPX4 on neurons from ALS mice. The result? ALS mice had lower levels of GPX4, and iron levels were dysregulated as expected. Overexpressing GPX4 in these mice showed a positive effect. There was a decrease in lipid peroxidation, therefore cell death was decreased, and disease onset was delayed thereby extending the mice’s lifespan. Additionally motor function was somewhat preserved although disease progressed as usual upon onset.

Does it really amount to much though?

These might not seem like groundbreaking discoveries. After all, the ALS mice still displayed neurodegeneration, indicating that we’re yet to uncover the full picture, let alone find a suitable long-term treatment. But we’ve made progress. Highlighting ferroptosis’s role in ALS opens up new avenues for treatments and discovery. Just from the researcher’s suggestions alone, perhaps selenium (a component of GPX4) or GSH treatments may be useful; iron chelation to remove excess iron might also hamper degeneration. Just knowing that ferroptosis exists and is involved in ALS gives us the power to target it in the future. Perhaps this is just the beginning. Ferroptosis is slowly being linked to other neurodegenerative diseases. Understanding it and how to influence it has the possibility of building the foundation upon which we can treat other diseases as well. Every step we take towards learning more and more about the diseases that plague us is a step towards building a world where people don’t have to suffer from them.

Reference

Wang, T., Tomas, D., Perera, N.D., Cuic, B., Luikinga, S., Viden, A., Barton, S.K., McLean, C.A., Samson, A.L., Southon, A. and Bush, A.I., 2022. Ferroptosis mediates selective motor neuron death in amyotrophic lateral sclerosis. Cell Death &
Differentiation, 29(6), pp.1187-1198

Are cerebrospinal fluid pharmacokinetics able to predict brain target concentrations of drugs?

by Bianca Rijkmans

Are the pharmacokinetics of cerebrospinal fluid (CSF) able to predict brain target concentrations of various drugs? What role does the blood brain barrier (BBB) play in the distribution of drugs within the central nervous system (CNS)? What is the relationship, in terms of drug distribution, between the different compartments of the brain? These are some of the questions explored in a review paper by de Lange and Danhof (2002).

Knowledge about distribution within the central nervous system is important for drugs that have brain target sites, such as antidepressants, anticonvulsants, anaesthetics, antibacterials and anticancer agents. In the clinical setting, direct measurement of the concentration of these types of drugs poses many challenges. Historically, most often drug concentrations within lumbar CSF were used as a proxy for the concentrations achieved in the brain – however the role of the blood-brain barrier and blood-CSF barrier in the complex relationship of drug distribution within the different compartments of the CNS requires further research. The compartments of note include the brain extracellular fluid (ECF), intra-cellular brain compartments, as well as ventricular and lumbar CSF.

There are multiple factors that may affect drug distribution within the CNS. Firstly, the blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) affect the entry and distribution of drugs into the different CNS compartments. The BBB is found at the cerebral endothelial capillaries, which have tight junction proteins that restrict the movement of mainly hydrophilic drugs. The BCSFB is slightly more permeable than the BBB. The characteristics of these barrier systems have significant implications for the distribution of drugs in the CNS. Secondly, there may be distinct differences in the pharmacokinetics of drugs within lumbar CSF compared to ventricular CSF, due to diffusion as well as CSF dynamics. Thirdly, in terms of the physicochemical properties of drugs, the size, charge and lipophilicity of the drug affect its ability to passively diffuse. In this case, lipophilic, small and non-charged drug molecules are favoured when it comes to transcellular diffusion. On the other hand, hydrophilic, large and charged drug molecules rely more on paracellular diffusion, although this type of transport is mediated by the tight-junctions of the BBB and BCSFB, that preclude molecular transport based on size. Cerebral blood flow could also affect drugs crossing the BBB, with an increase in blood flow resulting in a greater influx of highly permeable drugs across the BBB. In addition, the extent of plasma-protein binding of a drug will affect its transport across the BBB and BCSFB. The turnover rate of CSF will also have an effect. Enzymes found at the BBB and BCSFB affect drug metabolism, which acts as a barrier for drug entry into the brain. In addition, pathological brain conditions can affect the permeability of the BBB. This creates repercussions for the transport of drugs across the barrier into the brain. Drugs can also cross the BBB and BCSFB by active transport, which involves the use of ion channels and pumps, including influx and efflux transporters. Some endogenous influx transporter proteins may assist drug entry into the brain, and efflux transporters may actively pump drugs out of the brain.

Considering the multitude of factors that affect drug distribution within the different CNS compartments, it seems logical to try to find a method of measuring drug concentrations as close to their presumed site of action as possible. This is important for antibacterial drugs, where a minimum inhibitory concentration (MIC) needs to be reached in order to kill off the bacteria – for example when treating bacterial meningitis. If we are still only using lumbar CSF concentrations as a proxy for brain drug concentrations, we are in the dark about the actual drug concentrations being achieved in the affected brain tissue. This has significant implications for determining whether sufficient dosages are being prescribed in the clinical setting in order to achieve the best patient outcomes.

Most drugs that target the CNS have their target sites within extracellular regions, thus extracellular brain concentrations of these drugs provide the most relevant information. Cerebral microdialysis is a method, although invasive, that may be able to measure drug concentrations achieved at specific regions in the brain. Imaging techniques, despite having significant limitations, may be non-invasive methods for obtaining better drug concentration information as well. These techniques include positron emission tomography and magnetic resonance spectroscopy.

The review concludes that the value of CSF concentrations of drugs in predicting the effect of the drugs in the brain is highly limited, and thus methods to measure drug concentrations closer to their site of action in the brain need to be further developed.

Reference

de Lange, E. and Danhof, M., 2002. Considerations in the use of cerebrospinal fluid pharmacokinetics to predict brain target concentrations in the clinical setting. Clinical pharmacokinetics, 41(10), pp.691-703.

Early bird or night owl?

by May Krause

Do you consider yourself a night owl? Do you struggle to fall asleep and wake up early in the morning, hitting the snooze button a few too many times? This may be the cause of a genetic mutation, meaning we now have a medical excuse for missing that 8 am lecture.

Researchers from The Rockefeller University discovered a genetic mutation, altering the timing of the biological clock. The result of this is a common sleep syndrome called delayed sleep phase disorder (DSPD) or “Night Owl Syndrome”.  It is estimated that a whopping 15% of people in the United States struggle with this disorder.

Normally the intrinsic circadian clock promotes 24-hour rhythms, that are essential for daily human activity and body functioning. The 24-hour cycle consists of a negative feedback loop where transcription factors, Clock and Bmal1, produce inhibitors (of the Per and Cry family). These inhibitors gradually repress the transcription factors which are eventually silenced and therefore no longer produce inhibitors. Once all the inhibitors have degraded, the transcription factors regain their maximum potency, thus starting the cycle all over again.

The researchers sequenced the genes that form the mammalian circadian clock from the DNA of a patient thought to have DSPD. A mutation in the CRY1 gene was found, a gene already implicated in the circadian cycle. This gene mutation results in an altered protein expressed leading to the inhibitor being hyperactive. A hyperactive inhibitor causes the activators to be repressed for too long, extending the circadian cycle by at least half an hour.

To test whether the circadian abnormalities in this individual were related to the observed modification of CRY1, information on sleep patterns was obtained from the proband’s family members. The individuals were genotyped for the presence or absence of the candidate allele. Delayed sleep behaviour was found to be common among family members of both sexes and across several generations. This led the researchers to conclude an autosomal-dominant inheritance pattern.

So besides being an easy excuse as to why you overslept, this discovery may lead to the development of drugs in the future based on this mechanism that has been uncovered. Perhaps a drug that would reduce the activity of the hyperactive CRY1 protein in individuals with this disorder. Additionally, I believe that more research should be done around this since the human circadian cycle is known to not only regulate sleep but also hunger and levels of metabolites and hormones. How does the CRY1 mutation in people with DSPD affect this? Hopefully, the answer to this becomes clear soon, but until then I’ll carry on hitting my snooze button a few too many times. 

Reference

Patke, A., Murphy, P. J., Onat, O. E., Krieger, A. C., Özçelik, T., Campbell, S. S., & Young, M. W. (2017). Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder. Cell, 169(2), 203-215.e13. https://doi.org/10.1016/J.CELL.2017.03.027

NOTE TO SELF: You are growing and learning, it’s okay to fall but remember to get back up again.

by Thando Kubheka

With this piece, I am going to take you back to the very beginning and set the scene, it’s 2021, I am in my room preparing for the final exams of my undergraduate studies and I received an email that had me smiling for the rest of the day, it read: “Congratulations! You have been firmly admitted to the BMedScHons program at UCT in 2022.”

The day I arrived in Cape Town, from Joburg, was filled with so much anticipation, I had never experienced such a cocktail of emotions before, a mixture of excitement and joy laced with fear and anxiety. I got to my room at res and before doing anything else sat down and wrote down all the things that I was grateful for at that moment, little did I know that this would be an important grounding exercise for me throughout the year. This was followed up by me writing down my hopes and goals for the year on a blank A5 sheet. I put down a variety of things both academic, like
improving time management and asking as many questions as possible; and some personal things, like strengthening my relationships and working on my overall health through reading, journaling, and eating. I had placed this beautifully decorated sheet strategically on my wall so that it was the first thing that I saw when I woke every morning. I was fully prepared for the year ahead, or so I thought. The reality of what the honour’s year was to bring first hit me when I was faced with an excel spreadsheet titled “Student Year Planner 2022”, and I quickly realized that what I had ahead of me was a beast, truly going into the lion’s den and looked my little sheet and was filled with doubts, could I get through this? This question still looms over me as I write this.

As the real work began, I found it harder to stick to those goals I had written down. I could feel my mental health deteriorating exponentially, and with the people I love being so far away, I felt more alone than ever. For the first time it had got to me in such a way that I was unable to compartmentalize; separating my personal struggles and worries from my academic commitments/requirements became an incredibly difficult feat, and with this year being one that I
planned to find myself and determine whether this whole ‘being a scientist’ thing is really for me, you can imagine how heartbroken this made me feel because it made me think that maybe I wasn’t cut out for this. Nonetheless, I continued pushing forward and taking on each day and its lessons.

When the second half of the year started, I decided to revisit that list of goals I made and made the necessary adjustments that would allow me to be more flexible with the changes that come with this honour’s year. The old list is now stored away and now I wake up to see my new redesigned list of goals, it’s not as beautifully decorated but it is a better fit for the person I have grown to become. Despite the rocky beginning, this year has shown me just how resilient I am, I will not give up even when my world is literally shattering around me, which it has several times, and despite the pain and discomfort, I do believe that the struggles that I faced this year were necessary for me to truly
appreciate this trait in myself. I have also learned the importance of having a great support system, I had always thought this meant only my immediate family, but this year showed me that that support is through a variety of different people: from friends to lecturers to my incredible supervisors and lab colleagues who I truly appreciate for all their guidance and mentorship, and for handling me with such care and compassion.

I am going through the remaining months of this year, feeling immensely grateful for the lessons I have learned in and out of the classroom and lab. I’ve had the opportunity to learn many valuable lessons about myself and have met such amazing people who have shown me that what makes this life beautiful are those little moments in between the chaos, when you share a laugh with a friend, or when you have random dance parties as a mid-week pick-me-up to energize and relieve stress. So, with this last stretch, I want to allow myself to fall and get back up again, I want to open myself
up to more opportunities and forgive myself for the mistakes that I made while trying to figure things out because I am capable of achieving a lot more than I think or even believe sometimes.

And finally, thank you 2022 Honours year, you are truly a gift, I really see and appreciate that now.

The people behind the science

by Bianca Rijkmans

Patience. That is what the past couple of months have been teaching me. Patience. Waiting over 6 weeks for equipment to arrive in order to start your experiments for your thesis tends to do that, I think.

In the meantime, I have thrown myself into learning as much as I can with the research group my project falls under. They are the best bunch of people, all interesting and unique and kind and helpful. I got a teeny taste of what it is like working as a team sorting through old patient files and documenting certain details on a group spreadsheet, and enjoyed celebrating with everyone once the task was finished. We had a debrief session after this period of working through some pretty heavy and hectic patient files (mostly dealing with motor vehicle accident traumatic brain injuries) and it was a safe space to process the emotions of reading through the files over the past couple of weeks. I learnt about everyone’s different hobbies outside of the research space; they range from yoga, to dungeons and dragons, to sewing and baking. We talked about work-life balance, and coping mechanisms, and celebrated the birth of the baby boy of one of the researchers in the team. I think what I love most about science at the moment is the people, and how they can shape your experience of working in a lab. Interacting and getting to know different researchers and their stories has been the best thing, and I know that in whatever direction I take my studies, people will be a part of that story. I think this is really special and something to be treasured, along with scientific progress and academic accomplishments and all that. Isn’t there a saying that rather than what you did or said, people remember how you made them feel? Well so far I have felt very welcomed and encouraged working with this wonderful group of people, who also happen to be spectacular scientists I can look up to and be inspired by.

Okay, back to waiting for the equipment to arrive and stressing about my project…

Sometimes it is all in the tweaking – immunotherapy studies

by Gomolemo Molope

In school, it goes without saying that acquiring excellent marks throughout the year is a goal most students aim to achieve. However, there is a lot more to the honours year than just bagging distinctions and simply calling it a day – or rather one of the longest years. Some lecturers emphasize that this is a year where you get to expand your knowledge by delving into the scientific work which you find most fascinating; while learning some of the most important techniques researchers use to build this body of knowledge. My supervisor on the other hand refers to it as the year of “trial-and-error”. He says it is the year wherein you’ll gain some lab experience that will either make you joyful and proud or that will just make you cry and super stressed. I couldn’t agree with him more, especially while I was standing in the lab repeating an experiment for the fourth time!

I genuinely felt like giving up at that point. But following a series of numerous attempts at the same experiment, I eventually realized that simply adding a slightly higher volume of enzyme to my reaction tubes could have produced the best results. All I needed to do was to tweak the protocol. And much like me, researchers constantly find themselves having to tweak some of their techniques and protocols to produce effective treatments that aim to alleviate numerous diseases. For instance, acute myeloid leukaemia (AML). This blood and bone marrow cancer has limited treatments with high success rates due to their lack of specificity and their association with life-threatening side effects. Additionally, some of the available treatments cannot be administered to AML patients because they lead to graft-vs-host disease. Consequently, specific and more effective treatments still need to be produced to treat this cancer.

Recently, a much greater effort aimed at developing such specific treatments is being made. The latest research has revealed the use of chimeric antigen receptor (CAR) – T cells as an alternative and novel form of cancer therapy, which boosts the immune system to fight cancer. CAR- T cell therapy has shown exceptional success rates compared to conventional treatments as it targets specific antigens which are expressed by cells known to lead to the development of a particular disease. In some cases, researchers genetically modify natural killer (NK) cells as opposed to T-cells due to their cost effectiveness, reduced side effects and longer lifespan. For instance, work done by Albinger (2022) is proof of concept of a treatment which specifically targets AML cells. Essentially, they set out to generate CD33-targeted CAR-modified natural killer (NK) cells. They focused on CD33 because it is a potential antigenic target frequently expressed on leukemic blasts and cells that prompt leukaemia.

In order for Albinger (2022) to achieve their objectives, they first collected AML cells from patients and then isolated primary NK cells from healthy volunteer donors. They then tweaked or rather genetically modified (by lentiviral transduction) primary NK cells to express a second-generation CD33-CAR. In vivo functional studies of CD33-CAR-NK cells in humanized OCI-AML2 xenograft mouse models which reflect physiological conditions of a human host were
performed. Qualitative and quantitative analysis using flow cytometry and confocal microscopy were also done.

In the end, their work showed considerable results proving that the use of CD33-CAR-NK cells could be a potential treatment for AML. In vitro experiments, in the OCI-AML2 cell line, showed that the CD33-CAR-NK cells had stronger cytotoxic activity against AML relative to untransduced NK cells. The in vivo experiments where a single dose injection of CD33-CAR-NK was administered showed effectual clearance of leukemic cells and a greater reduction in leukemic burden relative to untreated mice or mice receiving untransduced NK cells. In vivo experiments where multiple doses of CD33-CARNK cells were administered also showed minimized leukemic burden. The confocal microscopy images obtained from some of the experiments showed low GFP-positive leukemic cells and the presence of intact CAR-NK in the bone marrow of CD33-CAR-NK treated mice. Another one of the major observations made from Albinger’s (2022) work was that the use of the single and repetitive doses of CD33-CAR-NK cells in the mice did not cause any noticeable changes in weight, appearance or behaviour. Additionally, no signs of cytokine release syndrome or graft-vs-host disease were observed.

In conclusion, the results prove that CD33-CAR-NK could be a suitable treatment for AML. Moreover, targeted therapies may assist in improving the prognosis of many patients with AML. This form of therapy could also be applied in the treatment of other types of cancer. However, further research about the identification of unique antigens needs to be done to produce more effective targeted therapies while minimizing undesirable side effects in patients.

Reference:
Albinger N., Pfeifer R., Nitsche M., et al. (2022) Primary CD33-targeting CAR-NK cells for the treatment of acute myeloid leukemia. Blood Cancer J. 12, 61.

THE MALE PILL

by Husnaa Bux

Despite medical advances, uneven access to healthcare still contributes to gender inequality. The female combined oral contraceptive pill has been on the market for sixty years and has empowered women, giving us autonomy over our bodies. As reviewed by Dr. Stephanie Page and colleagues in Frontiers in Endocrinology, the variety in female contraception contrasts with male contraception which consists of condoms, withdrawal, and a vasectomy. Only 16% of global contraceptive use is male-driven, with the ‘latest’ commercially available male contraceptive being the condom, which was established two hundred years ago. Inadequate male contraception emphasises how society places the responsibility of safe sex on women.

Though the proof of concept of androgen use to suppress spermatogenesis was established by the WHO almost fifty years ago, male hormonal contraception is unavailable and pharmaceutical companies have abandoned male contraceptive development. Predictive models suggest novel reversible male contraception could decrease unplanned pregnancies by 30 to 40%, improving the mental, physical, and economic well-being of women and their families, and decreasing population growth. The perceived lack of market for male contraception highlights the commercially driven pharmaceutical industry.

Surveys show that 50-85% of men are willing to use male hormonal contraception. To date, however, only eight male hormonal contraception efficacy studies have been conducted, some of which were terminated prematurely due to mood-altering side effects. An unequal standard of healthcare between genders is seen by the side effects of the female ‘pill’ which include headaches, nausea, weight gain, mood changes, and more. Dimethandrolone undecanoate (DMAU) is an oral and injectable male hormonal contraceptive that acts on both progesterone and androgen receptors. Studies show it is safe, well-tolerated, and markedly suppresses gonadotropins and sex hormones, with few or no symptoms of hypogonadism. Yet male hormonal contraception commercial availability remains unseen.

While men bear no risks of childbirth or abortion, women are forced to use contraception as the benefits outweigh the risks. The benefits may only outweigh the risks for men if there were additional health benefits, for example, reducing long-term disease risk. Prolonging development, for an expectation yet to be explored for women, augments the burden of responsibility of pregnancy that society has already placed on women, diminishing the reality of the “shared risk”.

Through education, increased awareness, and engagement of pharmaceutical companies, male hormonal contraception can be materialised. This will improve the health and wellbeing of women, and decrease global burdens.

References
• Page, S. T., Blithe, D. & Wang, C. 2022. Hormonal Male Contraception: Getting to Market. Front Endorcrinol (Lausanne). DOI: 10.3389/fendo.2022.891589
• Roberts, M. 2019. Male pill – why are we still waiting?. BBC News (online). Available: https://www.bbc.com/news/health-47691567.

From Jozi to Stellies to CPT – Stepping out of my comfort zone

by May Krause

I was born and schooled in Johannesburg. Big, bad, crazy wonderful Joburg, I was a Jozi girl through and through. When I moved to the quaint and historically beautiful town of Stellenbosch for university, I happily donned my Matie shirt and threw myself into my own independence. Last year, after graduating I was more than ready for a change. Two years of covid had exhausted me (and almost everyone) and I felt stuck in a time warp, with the same faces who still had one goal and one goal only, to party as hard as they could. I was over that and had been since 2020 when my degree kicked into a higher gear. So, with my 3-year undergrad coming to an end, I knew it was time to leave. I needed a change, a fresh start, a new view, another layer to me.

Cape Town was the next beautiful Western Cape destination for me. I had visited my UCT friends on weekends and was already halfway in love with the vibey atmosphere, incredible nature and too- numerous to name stunning views at every turn. Whether those be of the sparkling sea, the magnificent mountain, vineyards or bustling busy streets or markets. Moving here and starting my honors at a new university knowing no one both excited and scared me but it has been the best decision I have made.

From watching the sunrise while driving around the mountain to campus, to being in my happy space, the lab, and having catchups with the wonderful friends I study with – my days are filled with interesting, challenging, expansive learning and then sensory delights in the beautiful cape. I have grown so much, in all the ways that are important. I am studying and learning what I am most passionate about. I most importantly, to me, I am the happiest I have been in a while. So, for those out there that are worried about making a change, moving away from what you know or what may feel comfortable, just do it. You never know… it might just pay off with a bigger, brighter, happier more challenging, varied, stunning view.

Not waving, but drowning

by Husnaa Bux

The amalgamation of twenty-twenty and twenty-twenty-one can only be separated by levels of
lockdown, like waves of an unexpected tsunami – isolated, estranged, remote, and restrained.
Entering twenty-twenty-two, the anchors were loosened, masks were lifted, and we were able
to come up for air. Life returned, or rather resumed, to (a new) normal – yet I still feel
restrained. Waking up for eight am lectures seems almost impossible. I struggle to comprehend
the ease with which I sailed through twenty-nineteen’s daily eight am to five pm. After a single
hour in a lecture this year, I almost feel as if I deserve to take the rest of the day off. The beach
always looks inviting, but I cannot find the will to go as the afternoon traffic tests my patience.
Even the simplest activities, like standing in an elevator with another person, seem suffocating;
it’s almost as ridiculous as staying out later than midnight and not sleeping for at least eight
hours. Suffice to say, being locked up has had a lasting effect.


Although I was present on campus last year, crowds were sparse. Now, the newly fallen
regulations have created upheavals, with everyone wanting to be above board, leaving me
feeling overwhelmed. It seems I am sinking. The sentiment of feeling alone while surrounded by
people has become my reality.


Fortunately, Honours has made the adjustment slightly easier. Coming from my third year of
MBChB, I was concerned that my background was insufficient and that I would be drowning in
work. I questioned whether the science boffins would be welcoming or deterring; especially
considering my now questionable ability to socialise and connect with others as an estranged
being. To my surprise, not only have I made friends, but the workload is manageable. Hybrid
learning, both physical and remote, has given me the space I need to transition, while still being
engaged with others.


In many ways my balance remains slightly skewed. It feels odd to be achieving a postgrad
without an undergrad, but the increased freedom and decreased working hours, has allowed
me to navigate through this new normal. At times I feel as if the tides still pull back, but I
continue to paddle in search of more stable ground.

BMedSc (Hons) in Personal Growth

by Anna Jellema-Butler

I entered this Honours program expecting to walk away with the field-specific knowledge and technical skills required to become an excellent scientist. However, as I have come to realize over the past six months, the primary outcome of our Honours year has little to do with a degree in science. The real takeaway will be immeasurable personal growth that can be applied to any career field, relationship, or goal.

Among the skills we have developed are time management, data analysis, problem solving, literature searching and review, project planning and development, and – perhaps reluctantly – public speaking. Our analytical minds were ceaselessly engaged as we were pushed to think and write critically. For the first time in our academic careers, we took personal responsibility over our work and found independence in the laboratory. We built relationships with fellow students and supervisors that will persist beyond the boundaries of campus. Most importantly, we practiced perseverance and positivity in the face of many, many mistakes and failures.

Undoubtedly, a portion of our class will go on to studies and careers unrelated to medical science. Still, we will have been well-prepared by this Honours year. Because the true challenge it posed was not in completing the lecture content or solving the scientific questions posed in our theses. Rather, it was a challenge of personal character, and one which precipitated immense personal and skill-based growth. For this reason, I am confident that my peers and I have been well-equipped for our future pursuits, wherever they may lie!

Effects of Exercise on Metabolism: More Extensive Than Previously Reported

by Anna Jellema-Butler

Regular physical activity is known to have cardiovascular-protective action mediated by improvements in lipid profiles, blood pressure, body fat, and insulin sensitivity (1). However, a recent study in Cardiovascular Research suggests that the magnitude and extent of the metabolic benefits of exercise are much more profound than previously reported. These findings have important implications for the prevention of heart disease, type II diabetes, and other cardiometabolic diseases which, together, account for over 30% of worldwide mortality (2).

In this unique study, Koay et al. (3) invited a group of 52 male military recruits of similar age and body mass index to participate in an 80-day program of daily aerobic and strength exercise. Critically, the soldiers were housed in the same domicile, allowing for careful – and previously unprecedented – control of lifestyle factors such as diet, sleep, work environment, stress, and tobacco and alcohol use.

To track changes in metabolic health, the authors compared post-exercise levels of 201 plasma metabolites to their baseline values. Global metabolism was dramatically shifted in the trained soldiers (Figure 1), with changes observed across numerous metabolic pathways and at magnitudes and significance levels heretofore unforeseen.

The largest change was a significant reduction in various fatty acid and ketone body intermediates – two substrate classes that serve as key muscle fuel. This indicates an increased capacity for and efficiency of muscular fatty acid metabolism, and to an extent that has never previously been captured. In addition to improved lipid metabolism, elevated levels of arginine and related metabolites in the post-exercise metabolomic profiles signify increased vasodilation and blood flow, reflecting improved vascular health in response to exercise.  

The scale and scope of shifts in several other metabolite classes, including gut microbiome-derived metabolites, markers of proteolysis, substrates of coagulation, endocannabinoids, nucleotides, and markers of redox stress, were similarly unanticipated and may provide novel insights into the metabolic adaptation to exercise.


However, not all the soldiers experienced the same metabolic benefits as their peers. Interestingly, an attenuated or maladaptive metabolic response was associated with increased levels of dimethylguanidino valeric acid (DMGV). This result supports a building hypothesis that DMGV, a poorly characterized metabolite, may serve as an early biomarker of subclinical metabolic dysfunction and allow for early intervention in individuals who will require strategies other than exercise to improve their cardiovascular risk (4).

As the most highly controlled metabolomic analysis of exercise to date, this study reveals the true range and magnitude of the effects of exercise across diverse metabolic pathways. Regular exercise significantly improved the overall metabolic health of young males in just three months. This result solidifies physical activity as a cornerstone of cardiovascular risk-reduction regimes. Furthermore, considered alongside demonstrated benefits for fitness, body fat, sleep, mental health, and non-communicable disease risk (5), these findings reinforce the prioritization of daily exercise for the average individual in pursuit of longevity and quality of life.


References

1.       Nystoriak MA, Bhatnagar A. Cardiovascular Effects and Benefits of Exercise. Vol. 5, Frontiers in Cardiovascular Medicine. Frontiers Media S.A.; 2018.

2.       Bhatnagar P, Wickramasinghe K, Williams J, Rayner M, Townsend N. The epidemiology of cardiovascular disease in the UK 2014. Vol. 101, Heart. BMJ Publishing Group; 2015. p. 1182–9.

3.       Koay YC, Stanton K, Kienzle V, Li M, Yang J, Celermajer DS, et al. Effect of chronic exercise in healthy young male adults: A metabolomic analysis. Cardiovasc Res. 2021 Feb 1;117(2):613–22.

4.       Robbins JM, Herzig M, Morningstar J, Sarzynski MA, Cruz DE, Wang TJ, et al. Association of Dimethylguanidino Valeric Acid with Partial Resistance to Metabolic Health Benefits of Regular Exercise. JAMA Cardiol. 2019 Jul 1;4(7):636–43.

5.       Ruegsegger GN, Booth FW. Health Benefits of Exercise. Cold Spring Harb Perspect Med [Internet]. 2018 [cited 2022 Aug 31];8. Available from: http://perspectivesinmedicine.cshlp.org/

The Covid Storm

by Pearly Joubert

An unexpected storm
Wild and unpredictable
Such an unusual form
But undeniable


Wind, hale and rain
Increasing world-wide pain
Help! The children are crying
Scientists and doctors were trying
But Covid couldn’t care less; did its best,
And put people to rest


Hospitals overcrowding
Made the beds limited
Businesses drowning
Humans became intimidated


So, we created lockdowns
Morning, afternoon and evening, we stayed in our gowns
Working from home
Having zoom meetings with colleagues from Rome
Every five minutes, washing our hands; trying our best
To not let Covid, put us to rest


Unfortunately, the rate of mutation,
created a Beta, Gamma and Omicron nation
Wearing masks couldn’t even make the storm end
Covid made sure it became a legend.

Friends became round icons on a screen
Some lecturers became a meme
WhatsApp became my hang-out spot
And although Covid is smaller than a dot
Its impact greater than a storm
Covid became our norm


Despite it all, I had time to look at the stars
Also, read about Elon Musk and Mars
I could spend quality time with my sister
Which usually only happened end semester
Almost beat my dad at chess
And helped my mom clean up the kitchen mess


There were conspiracy theories
Bill Gates using vaccines to implant microchips
Storming influx of online queries
We realized the need for improvement in our leadership
Learn from our history
To prevent a similar catastrophe


We can now un-mask?
I heard everyone ask…

Growing with Science

by Keegan Mills

Transitioning from medicine to science this year has been interesting. I have found that science has involved more thinking, understanding and application as opposed to the memorization that is required in medicine. I have been tasked with analysing and interpreting data this year and learning about and figuring out how different experiments work and how they can be used to answer specific questions which has required me to do a lot of my own research and learning so that I was able to understand the experiments and report back on them to my peers. Being challenged and having to apply myself in this way is something that I have enjoy and it has grown my interest in science and spurred me to want to continue my scientific journey and become a future clinician-scientist.

I have read many, many journal articles this year which has proved to be a valuable learning experience. In the past when I would read articles I often would struggle to understand and interpret the results confidently because of my lack of understanding of how the experiments that were done worked and how they could be used to prove a hypothesis.  Through my learning of various scientific techniques this year, I am now able to read papers confidently and can interpret the message they are trying to convey. Not only that, but I am much better at identifying bad science and when things aren’t quite adding up in a paper, which is an important skill to have.

Engaging with my research project has been frustrating. You can spend hours working on an experiment and do everything you needed to and when it gets right to the final point where you just need to quantify your results using various scientific equipment, you can get no data. This has happened a couple of times to me and it has been very frustrating. It is very different from medicine  where you know what you need to do and what is required of you academically and so the responsibility is on you to do what is required or not, things are in your hands and control (most of the time anyway). But such is the nature of science, things don’t always go to plan.

Working with different personalities for presentations and projects has also presented its challenges with people only wanting to work at certain times of the day or to work independently and just submit their portion of work. Navigating these situations and finding common ground has been a good experience to have to help develop my future leadership capabilities.

2021: The year I stepped into my power

by Samantha Kuphe

Honestly, the first 3 years of my undergraduate were filled with experiences attached to a lot of regret. I was leading my life based on the lives of my friends and my personal growth and goals took a backseat. I remember consoling myself saying ‘this is what university is for, to completely live like there’s no tomorrow and to enjoy my youth’. Little did I know that I was due for a rude awakening.

Toward the end of 2019 I was slowly losing interest in my degree. I put enough effort just to pass and on days where I did want to excel, I was subconsciously limiting myself. When I moved out of residence and rented a house with my friends in 2020, I thought life would get better and I would become dedicated again. However, as the pandemic began, I found something to blame for my lack of passion. I mean, the world felt like it was ending so why did I have to try.

But mid 2020 something very interesting, confusing, and challenging started to happen to me. Having more free time and less distractions I began a journey of introspection. I started feeling like I’m missing out on something great, like my life purpose was rapidly diminishing. I felt strongly drawn to figure out who I am and what I want out of life. As I started reading self-help books and listening to podcasts, I was reminded of all that I had to be grateful for and not take for granted.

Fast-forward to the beginning of 2021 I decided to rent a space to live alone, I needed complete isolation to re-invent myself and step into my power. That was the best decision I have ever made. The rest of the year was filled with moments of clarity, drive, and many opportunities to elevate my personal and career goals. That year also taught me that leading a balanced life is a lifelong journey that requires effort but is rewarded with many benefits.

Struggling to study? Try out Spaced Repetition Learning

by Ashraf Moosa

University students spend much of their time studying and preparing for exams. The transition from high school to university can be quite challenging with the increased volume of work and demanding time pressures. Many students struggle to get through vast amounts of content before an exam. However, a solution touted by many is spaced repetition. The idea of spaced repetition has its origins in the late 19th century when Hermann Ebbinghaus proposed a ‘forgetting curve’ (Figure 1). He noted that “frequent repetitions are indispensable in order to make possible the reproduction of a given content” (Ebbinghaus, 2013). Spaced repetition is a learning technique usually performed with flashcards. Flashcards are repeated at intervals to consolidate learning. Newer or more difficult flashcards are shown more frequently, while older less difficult flashcards are shown less frequently. This supposedly makes learning
more effective and efficient. However, is there any scientific evidence to support this technique and might it be the magic bullet to solve students’ studying woes?

A study in Australia by researchers Anton Lambers and Adrian J. Talia sought to answer this question. Their study, titled: “Spaced Repetition Learning as a Tool for Orthopaedic Surgical Education: A Prospective Cohort Study on a Training Examination”, aimed to determine the effectiveness of spaced repetition learning in postgraduate surgical trainees studying for an orthopaedic basic sciences examination. The study consisted of twelve participants who were prospectively enrolled in the study and were provided with a set of 1400 practice flashcards to use through the learning program Anki. Anki is a free and open-source flashcard programme that uses spaced repetition algorithms to enhance learning. The programme is able to track studying habits. Thus, the researchers collected data on time spent using the Anki programme, time spent studying per day, number of reviews performed per day, total number of cards reviewed, and the maturity of studied cards. After the students had written the examination, the researchers collected each student’s examination score. The researchers could then correlate the time students spent studying and the number of flashcards they reviewed with their test scores.

Out of the 12 participants of the study, 11 passed the examination. That represents a 92% pass rate, which was much higher that the overall national pass rate of 67%. It would appear that the participants fared much better than others that had not used the spaced repetition technique. This goes to show that it was effective. It was also interesting to note that the participant that did not pass the examination had only undertaken 1 hour of study time on Anki. This was well below the average of 30 hours other participants had used the programme for. The researchers found a strongly
positive correlation between time spent on the Anki program and final examination score (Figure 2). This supported the researcher’s hypothesis that spaced repetition learning using a flashcard format is an effective study strategy for learning material for Orthopaedic examinations. However, one can more broadly conclude that spaced repetition learning is an effective learning strategy for any fact-rich subject.

Whilst the results of the study are promising, it is limited by its small numbers and the fact that it was not randomised which opens it up to selection bias. In addition, the participants may have employed other studying techniques in conjunction with spaced repetition to prepare for the examination. Despite this, the findings of this study may
be of particular interest to students and those in the education community. Spaced repetition learning offers a way to learn faster and more efficiently. This would be of benefit to time-poor learners who want to maximise their learning from the limited time they have to study. Additional research is needed to further elucidate the benefits of spaced repetition learning, but why not try it out for yourself and see if you find any difference in your results?

References:
• Ebbinghaus, H., 2013. Memory: A Contribution to Experimental Psychology. Annals of Neurosciences, 20(4).
• Lambers, A. and Talia, A., 2021. Spaced Repetition Learning as a Tool for Orthopedic Surgical Education: A Prospective Cohort Study on a Training Examination. Journal of Surgical Education, 78(1), pp.134-139.

The difference between undergraduate and postgraduate studies

by Warwick Pitman

My honours year thus far has been a very different year compared to my years as an undergraduate. The first thing I noticed is that there is more freedom given to students to learn about the science they want to learn about. I often found myself going down different rabbit holes, spending hours reading up on topics that I found particularly interesting. An example of this was an obsession I developed with axolotls during my regenerative medicine module. I also quickly noticed that more responsibility is given to honours students to enhance their learning. I think one of the reasons that permits this is that there is a step away from being so mark obsessed, therefore as an honours student one must have the desire to perform as well as one can in presentations and assignments for the sake of one’s growth as a future scientist rather than for the mark one will achieve. Another obvious reason is the requirement for one to do a research project, where you determine how much literature you want to read and therefore learn. This is very different to being given a set of lectures to learn from, which is of importance at an undergrad level, to learn the language of the field and different forms of evidence, but I do believe it limits one’s capacity to learn as most students only focus upon learning the lecture content that they will be tested on.

During the module component of the course, we did receive lectures, but were most often assessed via presentations. My favourite assessments were coming up with project proposals and then presenting your ideas to the class. In this way one uses the experimental techniques taught in the lectures/discussions and then applies them to an area of research to find something novel. I loved these assessments as I felt like a scientist. Someone that reads the literature, identifies gaps, and then considers experimentally how one would fill the gap whilst also being aware of experimental limitations.

Another aspect that I have enjoyed about my honour’s year is being integrated into a lab. It is enriching to be around masters students that help teach you the different techniques they have learnt over the years and often serve as a guide considering that they have already completed their honours. Also, I cannot forget to mention the impact my supervisor, Dr Mubeen Goolam, has had on my honour’s year. He has always replied promptly to my emails and been available for meetings whether they are online or in person to discuss my project. Whenever I speak with him, I try to take in as much information as possible considering he has already got some of his work published in impressive journals such as Cell and Nature whilst working under professors that have contributed tremendously to the field.  

Overall, the difference between an undergraduate and a postgraduate degree has enhanced my growth as a future scientist in the world of research and has provided me with greater clarity on whether I want to engage in a career of research.   

No thesis is worth your sanity

by Kaitlyn Sparks

There is a test tomorrow. It looms in front of you. Nothing exists but the slides containing the information that surely should be in your brain by now. Your research write-up is due next week. You can’t bear to think about that right now. Assignment deadlines accumulate like neutrophils around you. All there is to do is to try not to be engulphed.

Unfortunately, the line between coping and not coping is a thin one. A line that undulates and shifts with every passing hour. One moment you can be doing well, and the next, a small task can feel impossible.

Often, at this level of academia, our self-worth is intimately linked to our success in classes and research. From the first time we set foot in primary school, we are often taught that academics are at the top of the priority list. Even if we are told that other things are more important, there are many non-verbal signals that imply the opposite.

In addition to this, getting to, and staying in, university is not easy. Many sacrifices are made, not just by us but by the people we care about. The pressure that comes with this is immense. Often, we can feel like we are representing the hopes and dreams of everyone around us. Thus, when things start to slip in this and other areas of our lives, it can feel like the whole world is ending.

Unfortunately, not many people speak about how difficult it is to maintain your mental health while in university. It has become better in recent years, yes, but it is far from being an open topic. That is why I am writing this piece: in the hopes that it will spark an open discussion in the academic space.

It should not be controversial to say that your mental health should come before your academics.

No grade is worth your mental health.

No thesis is worth your sanity.

No degree is worth your life.

Edging closer to an idea popularized in science fiction: the culturing of embryos outside of the mother’s body

by Warwick Pitman

Both my favourite science fiction novel, Brave New World, and science fiction film Blade Runner 2049, depict a reality in which ‘humans’ can be cultured outside of the mother until the end of embryonic development. The idea stems from the allure of potentially hacking biology in a way that allows humans to create organisms with preferable capabilities. If that isn’t a recipe for a perfect science fiction novel or film, I don’t know what is! With the discovery of genetic engineering tools such as CRISPR-Cas9, the idea of introducing specific changes into the genome has indeed become a reality, but what about the culturing of embryos outside of the mother’s body? Recently a study published in Nature shows that although we are far from this reality, we are a step closer to achieving this controversial yet remarkable feat. The authors established a system that allows for the culturing of mouse embryos from an early point in embryo development, specifically known as gastrulation, through to a point at which organ development occurs.  

The purpose of developing such a culture system is to help elucidate the developmental processes of tissue and organ formation during embryo development as these processes are difficult to investigate inside the body because they occur after implantation of the embryo. An analogy for this could be a little mole that one can observe and study when it is above ground but is actually most interesting to study when it burrows itself underground where they are adapted to hunt and create tunnelling networks. The same can be said for the embryo after it embeds itself within the uterine lining of the mother, as this is when the body axes of the embryo are established and where cells change in multiple ways to form the different organs of the body.

Since the maternal environment provides the embryo with specific nutrients and availability of oxygen to aid development, the authors had to attempt to replicate this environment as accurately as possible. This was accomplished by testing different media, supplements, and pressures, before ultimately finding the goldilocks conditions that supported the growth and correct development of the cultured embryos. The authors then provided evidence that the cells of the cultured embryos expressed the same genes as those found in embryos that developed inside the mother. This suggested that the culture system was not interfering with the normal development of the embryo and therefore could be used as a tool to recapitulate what occurs within the maternal environment.

One of the major implications of the system, that the authors make mention of, is as a tool to determine the effects of different perturbations on development of the embryo. This was something Aldous Huxley, the author of Brave New World made use of, to differentiate the castes formed in his dystopian novel. For example, oxygen deprivation and alcohol treatment are used in the novel to lower the intelligence and size of individuals of the lower three castes (Gammas, Deltas and Epsilons). In contrast to this, the motives of the authors of the Nature paper are ethically superior, as they contemplate using such a system to better understand the processes leading to the formation of organs through genetic modification which can have therapeutic applications. One of which would be its use in the field of regenerative medicine, as by understanding the molecular cues that orchestrate the development of an organ can provide insight into how one could regenerate it following an injury. To better understand this idea, one could view each organ of the body as a specific building each with its own architectural plan. If you knew the exact amount of brick, wood, and glass that was used to assemble the structure, it would be much easier to rebuild it, should it ever get knocked down.  

Overall, the study established a system that prolonged the culturing of embryos outside of the mother to a point in embryo development never observed before, but also showed the current limitations in executing what was described and depicted in Brave New World and Blade Runner 2049, respectively. This may be a good thing, as with such great power comes great responsibility, and whether our society would want such a culture system to be available for use is questionable considering the dystopian worlds developed in such novels and films.

Reference:

Aguilera-Castrejon, A., Oldak, B., Shani, T. et al. Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis. Nature 593, 119–124 (2021). https://doi.org/10.1038/s41586-021-03416-3

The Real Heroes of Universities

by Sharief Hendricks

The real heroes (or heroines if you like) of our tertiary institutions are the administrators and support staff. And like true heroes, their superpower often goes unnoticed, unrecognised.

No doubt, a University will not function without the work of the administrative and support staff. Our research, travel, teaching, and every day would not be possible.

The superpower though, is the care, kindness and generosity in their work. Work that is aimed to help us achieve our goals.

This time of the year, as we process postgraduate applications for the upcoming year, I always remember the kindness and generosity of our Faculty’s Postgraduate Office when I was a student applying to the Honours programme (back in 2007). The Postgraduate Office frequently shares this fond memory with me, a memory that serves our current working relationship well.

I always needed help with my student administration, and visited the Postgraduate Office more than usual, which I think provided me with the opportunity to experience their superpower. I can’t help wonder though, in today’s age, where everything is online and most communication takes place via email, are students and staff missing out on similar opportunities?

I have many stories similar to the above, where the care regularly goes beyond the call of duty. A more recent example is my trip to a conference in Monaco. On the Saturday, the last day of the conference, South Africa was issued a travel ban and my flight home got cancelled. True to form, my heroes emerged, and what could have been a complete nightmare without their kind and generous support, finding my way back home turned out to be somewhat of an adventure instead.

Have you experienced the superpower of your administrators and support staff? Please share.

As thanks for their work, I wanted to end off with naming all the administrators and support staff that have used their superpower to help me achieve my goals, like an author list on a paper. I decided against this though, in fear of missing a hero (and there are many heroes to mention). Also, like many of our favourite fictional superheroes in suits, anonymity is not a bad thing. So I’ll simply end with thank you.

In my own bubble

by Kaylene Baron

What makes the university experience more valuable is time spent with classmates and other students outside the lecture theatre. Due to COVID-19, that was minimal as all our lectures were online. With only a select few that were in person. Whenever we have a contact lecture or contact meeting, we have to wear masks. Needless to say, it is very uncomfortable for me. The reason is, if I do not know the people, then it leaves a very unsettling feeling inside me.

This year has just been eating, sleeping, work repeat with time for nothing else in-between. Even when we started with lab work, it was still very isolating as we are all trying to avoid contact with people.

For me, I am extra dependent on my peers for emotional support as I am a first-generation student. Meaning that I am the first person in my family to attend university, much less to obtain a postgraduate degree. Hence why getting emotional support, encouragement and motivation were very challenging. Yes, there is social media but in-person interactions for me at least, are much better. The ever-changing lockdown levels also aggravated it as it affects how much time I have in the lab, and how quickly I need to commute home when necessary. Nonetheless, even if it was virtual for the most part, I know that all my classmates and friends were supporting me in spirit

The New Genetics of Intelligence (Robert Plomin and Sophie von Stumm)

by Saleha Suleman

For centuries, humans have been defined by how intelligent they are. Although the definition of intelligence has changed with evolving times and the differences in lifestyles, the importance of intelligence has not. It is a predictor for occupational, health and overall quality of life outcomes, more than any other trait. This is because a higher intelligence involves the ability to adapt to quickly changing circumstances and undertakings that one would face in their work.

Worldwide, the most standard and widely accepted measurement for intelligence has been IQ (intelligence quotient). An IQ test is able to quantify a person’s reasoning and problem-solving abilities through various tests that the person goes through, and so should be able to account for creativity, thinking outside the box as well as skills needed in schooling subjects such as mathematics. The genetics of intelligence, however, has eluded humans for the longest time. Judging from simple logic, it can be said that there is a certain component of intelligence that is hereditary. But how much it is, and whether it outweighs other factors such as family support, schooling, socioeconomic status and others has not been determined yet. Simply put, intelligence is one of the facets of the ‘nature versus nurture’ debate.

In this paper, the authors performed a meta-analysis to accumulate the findings thus far of the effect of genetics on intelligence. They did this by reviewing results from initial genome wide association studies (GWAS) and showed how genome-wide polygenic scores (GPSs) are a better predictor of intelligence due to it’s accuracy and ability to measure the effects of thousands of DNA variants that are associated with intelligence.

The main findings of the paper are presented in the infographic bellow. Since this is a review, the authors confirmed that there have been multiple attempts to gauge the effect of genetics on intelligence, but the most recent success has come from the use of GPSs. At the time this paper was published, there was also a much larger scale GWAS study being performed that would allow identification of up to 10% of variance. Such studies would allow a clearer definition of the relationship of intelligence with socioeconomic environment, family support, educational attainment of parents and other environmental factors that have so far been attributed to nature in the nature versus nurture debate.

It is important to remember that such studies, and even any tests that would be available to take at a clinic for example, would still be probabilistic and not determinate. Because of that, despite the potential to understand the human mind more, as well as the fact that understanding measurable outcome differences in people of different genetic intelligence would be revolutionary, there have been major ethical concerns for these studies. These include four; biological determination and potential for stigmatization and discrimination, both which can see people being afforded opportunities such as in careers or social circles because of their genetic intelligence, ownership of information, and finally the emotional impact of knowing one’s own personal genetic intelligence levels. As results from current studies become available, it will be of utmost value to distinguish the benefits and shortcomings for them.

References:

Plomin, R. and Von Stumm, S., 2018. The new genetics of intelligence. Nature Reviews Genetics, 19(3), pp.148-159.

Running and Patellofemoral Pain Syndrome: What makes you weak at the knees? — Rugby Science

Patellofemoral Pain Syndrome (PFPS) is a knee condition associated with anterior knee pain when loading the knee in movements like squatting, stair climbing, running and jumping (Ferber et al., 2015). Due to its high prevalence and running becoming an increasingly common form of exercise, it is important that high quality evidence regarding treatment and preventative […]

Running and Patellofemoral Pain Syndrome: What makes you weak at the knees? — Rugby Science

DOCTRINE OF SIGNATURES (You are what you eat)

by Sedzani Mbedzi

The doctrine of signature is an ancient pharmacological theory which states that the way plants look, taste, react or shaped offers strong clues to their medical implications. Major category of doctrine of signature are the similarity between shape of the plant and ailing human organ, and the similarity of plant colour to disease syndrome. Indigenous people coined the concept “you are what you eat and so is the brain” which suggest that what you eat is valuable to your health and heart. They had a well versed and in-depth understanding of nature, and knowledge about how some plants work and what they are used for. Physical characteristics of plants reveal their therapeutic value, for instance the reddish color of beetroot (blood root) indicates the plant’s efficacy in treating blood disorders.

Pomegranates resembles the human heart and known to have rich antioxidant polyphenols, which includes tannis, anthocyanin and flavonoids. Study by Dos Santos and co-workers reveled that having pomegranates at least once a day can be significant in attenuating hypertension, stress level and making your skin glow (Dos Santos et al., 2016). Using pomegranate dried peels, extracts for dietary purposes attenuates stress and coronary angiotensin converting enzyme (ACE) activity. ACE is a zinc metallopeptidase comprised of two homologous domains, the N and C domain. These domains are the main targets of ACE inhibitors that act by binding to the zinc. Polyphenols have chemical structures that favor chelation of redox active metals which favor ACE inhibition. This fruit lowers cholesterol, blood pressure and melts away heart blockages.

Figure 1: Infographic presentation of pomegranate resembling a human heart with chambers inside and the seeds encased like blood vessels. Pomegranates contain punicalagins that benefit the heart and blood vessels. The fruit lowers cholesterol, blood pressure, and melts away heart blockages.

“You are what you eat” concept plays a crucial role in managing chronic diseases. Therefore, it is important to know what you eat and how that impacts your body. It is quite difficult to eat healthy under stressful situations. For instance, during examinations a lot of university students tend to eat more fast food and snacks. The doctrine of signature indicates that having healthy snacks such as walnuts regularly may improve brain health and reduces risks of heart disease and cancer. Figure two below just shows some of healthy food and organs that they resemble.

Figure 2: info graphic representation of certain medicinal plants (fruits and vegetables) and resemble organs that they are good for.

Studies suggest that doctrine of signature could be the future for development of effective drugs and reducing chronic illnesses. For instance, beneficial effects of pomegranate peels extracts may be considered in development of therapies for hypertension.

REFERENCE

Dos Santos, R.L., Dellacqua, L.O., Delgado, N.T., Rouver, W.N., Podratz, P.L., Lima, L.C., Piccin, M.P., Meyrelles, S.S., Mauad, H., Graceli, J.B. and Moyses, M.R., 2016. Pomegranate peel extract attenuates oxidative stress by decreasing coronary angiotensin-converting enzyme (ACE) activity in hypertensive female rats. Journal of Toxicology and Environmental Health, Part A79(21), pp.998-1007.

2021 Dissections

by Astrid Kühn

The first part of my year was spent in the pam lab, a small dissection hall, a temporary home to six bodies. My initial feeling upon entry to the lab was that this was a sacred space, housing those who had made a huge and noble sacrifice in their death, to teach someone like me a lesson in anatomy.

In the weeks to come, I would learn that my idea of the dissection hall was naïve and romanticised, some of the bodies are actually unclaimed- unknowing of their fate during their lifetime. It was advised by one of my lecturers that due to certain characteristics of the body assigned to my study, he was most likely one of these unclaimed people.

I began to feel that every mark I made on his body was a mark I did not actually have permission to make. It is common for students to name their bodies due to the amount of time spent with them and the strange intimacy foundered. But who was I to name someone who already had a name, to superimpose my own narrative onto a body whose soul I already felt unhappy, restless and turning? The more I dissected, the more I became cognisant of the fact that I had no clue what he had been through, what these hands had held, lost, hurt, cared for, perhaps prayed to. My familiarity with him was always marked with a respect, he was a stranger, a reluctant participant in my well-intentioned butchery. He will be cremated at the end of October 2021, his ashes scattered in a barren garden, unbeknownst to his loved ones- if he had any. I still feel a profound sadness and guilt for my part in the violation of his body, the vessel that carried him for a lifetime. However, through his circumstance I am reminded of my privilege, not only to learn anatomy in this deeply intimate way but for the support of my loved ones- a blessing I still, somehow, wished for him.

A LETTER FROM THE FUTURE YOU

by Lwanda Ndwandwe

To whom it may concern

It took me a while to figure out what I could say my honours year has been like, I’ve had so many mixed emotions and I haven’t taken the time to process everything. So instead, I thought to write a letter, a letter to myself 6 months ago, and to those who’ll soon find themselves on this incredible journey.

“Honours will be honours”, I am sure you are probably tired of hearing this line but trust me when I say you will grow to understand it. The honours programme itself needs you to be fully prepared not only to work hard but smart, it comes with a lot of exciting and different content that you will be engage in which will challenge your thinking while shaping you for the field ahead. The year will be a different experience for everyone, it may be difficult to adjust both to the environment and the work but keep in mind that this is all part of the process. While trying to be productive and on track with everything I had to learn these 4 lessons below, that may seem silly but really helped to keep me calm and enjoy the year thus far:

Lesson 1: It is okay to not be okay, please read that again. This year is meant to be challenging bringing you out of your comfort zone, but with that comes growth.

Lesson 2: Set a timetable and stick to it, this will help you stay ahead while being productive with your time. There will be activities, lab work, a project, individual and group assignments that will be expected from you, multitasking comes into play and this will be highly effective if there is a schedule/ timetable to work with.

Lesson 3: Give yourself a break, add it to your timetable, whether it’s a walk or going out for lunch it’s easy to forget to take a moment off your laptop or cellphone, so go outside and breath.

Lesson 4: Enjoy the process and the pressure it comes with; the year goes by so quickly and before you know it, you’re sitting in your room wondering where the time has gone.

Overall, this year is going to be an adventure filled with excitement, tears, disappointments, procrastination, self-doubt, great achievements, and most importantly new skills and greater knowledge; and through all this don’t forget to take care of yourself.

Warm Regards,

A Proud honours student

Genetic data and Global populations: Do we have enough data to do a genetic study on the correlation between mental illness and drug use in a South African population?

by Mellie Msipa

Studies into Crystal Meth and its association with Schizophrenia

We all know that drug abuse is “bad”. Cocaine, Benzodiazepines and Methamphetamine (Crystal Meth) are just some of the drugs that people abuse, and if you were like me and grew up around people that weren’t always politically correct, then you probably heard the saying that ‘drugs kill your brain cells, and make you mentally ill’. Although phrases like this are often thrown at children and adolescence as a scare tactic to deter them from experimenting with opioids, some researchers in South Africa, Germany and the United States may have taken it quite literally, when they investigated and later published their paper on, “Schizophrenia Polygenic Risk and Brain Structural Changes in Methamphetamine-Associated Psychosis in a South African Population” (Passchier, et al., 2020).

How was the investigation conducted?

Saliva samples were collected for various cases and controls. The cases included patients that had Methamphetamine-associated psychosis (MAP) and patients who had a methamphetamine dependence (MD) and no psychosis. Healthy controls (HC) were also investigated for comparative purposes (Passchier, et al., 2020). The samples were genotyped, and quality control was performed on the data. Principal component analysis was performed to account for stratification, Structural brain imaging was performed to investigate the brain regions that have been linked to MAP and schizophrenia (Passchier, et al., 2020). Polygenic risk scoring was performed to determine the effect of the risk variants on the phenotype/ disease. Statistical analysis was then performed using tests, one of which included a t-test that tested the differences between the two case groups and the healthy group.

The results found the following:

The aim of the study was to determine how the polygenic risk scoring data from a European ethnicity based GWAS study on MAP compared with the brain measurement volumes tested in the South African MAP patients (Passchier, et al., 2020). The results of the investigation showed no significant association between Schizophrenia-derived risk scoring and the MAP disease diagnosis in patients.

The researchers also found that there was no correlation between the polygenic risk scoring and the volume measures from the different parts of the brain in the patients. The paper explains that that the negative result could be since Schizophrenia polygenic risk scores have no relation to the brain volume measurements seen in the case samples (Passchier, et al., 2020).

Due to the lack of GWAS data available for patients of African descent, the researchers found that people of African descent had the lowest polygenic score performance, and they concluded that the Polygenic risk score data from European population based studies were not applicable for the South African patients studied in this paper (Passchier, et al., 2020).

Ultimately the results for the study were inconclusive due to the limitations due to sample size, stratification bias and the risk of misclassification from the diagnostic interviews.

Impact of this research:

African health care systems like South Africa saw that mental and substance used disorders like schizophrenia increased by over 50% in the different populations just between the years 2000 and 2015 (Sankoh, et al., 2018). Diseases like Schizophrenia have led to over 14% of deaths globally and previous studies have found 145 genome wide significant loci for Schizophrenia ( Stevenson, et al., 2019). Mental health is a global problem, however very little genetic data is available/ recorded for mental health diseases that plague non-white populations. While the results of the study could not show any strong correlation between Schizophrenia and Crystal Meth use, the design of the study highlighted the need for more studies into non-European populations, like African populations that could uncover new risk variants.

References:

Stevenson, A. et al., 2019. Populations-Psychosis (NeuroGAP- Psychosis): a case-control study protocol and GWAS in Ethiopia, Kenya, South Africa and Uganda. BMJ, Volume 9, pp. 1- 9.

Passchier, R. V. et al., 2020. Schizophrenia Polygenic Risk and Brain Structural Changes in Methamphetamine-Associated Psychosis in South African Population. Fronteirs in Genetics, Volume 11, pp. 1- 7.

Sankoh, O., Sevalie, S. & Weston, M., 2018. Mental health in Africa. The Lancet Global Health, Volume 6, pp. 954- 955.

Burn wounds and P-fibrin

by Alexander Geragotellis

Background:

Burns are a global public health challenge and claim the lives of ±180 000 people each year [1]. The vast majority (±90-95%) of these deaths occur in LMICs and disproportionately afflict African children under the age of 5 years, who carry double the incidence of burn deaths compared to children under the age of 5 years worldwide [1]. Despite the extensive catalogue of burn wound coverage options, skin repair could still be defective owing to the complexity of the healing process. Cell-mediated treatment achieved through bioengineered constructs may provide alternative and more effective avenues to resolve burn wounds. Hydrogels are valuable tools in tissue engineering and regenerative medicine for stabilising tissue, and for delivering growth factors, bioactive ingredients and stem cells. The polymers used to make hydrogels can be natural [2], synthetic [3] or hybridised using both polymer types to infuse the desirable properties into one construct. The group who published the current research paper have previously reported on the advantageous properties of the poly(ethylene-glycol)-fibrin hybrid hydrogels [4]. Figure 1 offers a resource with further clarity on relevant tissue engineering terminology.

Aim:

The current study [5] aimed to evaluate the burn-wound healing potential of a bio-engineered 3D PEGylated-fibrin (P-fibrin) hybrid hydrogel as a scaffold to deliver adipocyte derived stem-cell (ASCs) using a rat model. The synthesis scheme has been summarised in Figure 2.

Figure 1 – Glossary of useful terminology to guide interpretation of the paper and results.

Figure 2 – Synthesis scheme for the ASC-embedded P-fibrin hybrid hydrogels used in the study [5]. ASCs were embedded within the hydrogels to try further augment the pro-regenerative activity of the P-fibrin hydrogels.

Objectives:

Methods used to achieve objectives have been summarised in Figure 3. By comparing burns wounds (i) untreated, or treated with either (ii) P-fibrin or (iii) P-fibrin with embedded ASCs between 7-21 days post- burn injury, authors set out to determine:

  1. Whether or not the application of the gels negatively affected burn wound closure.
  2. Characterise wound coverage and wound integration of the hydrogels using light and fluorescent microscopy.
  3. Explore angiogenic potential via immunohistochemical analysis of burn wounds to quantify blood vessels.
  4. Evaluate macrophage activation status of regenerating wounds, and how it is impacted by hydrogel application using immunohistochemistry.
  5. Assess collagen deposition and organisation 21 days post-injury to understand longer-term recovery phenotype.

Figure 3 – Rat burn model, adapted from Chung et. al [5], and accompanying methodologies used to achieve the objectives of the study.

Take home messages:

  • The major value of using a P-fibrin hydrogel appears to be with the increased cellularity of the granulation tissue at one week post-burn, suggesting an increase in tissue regeneration capability. The increased cellularity was similar to that observed when the P-fibrin was embedded with ASCs, indicating that the scaffold itself was the responsible factor and that the ASCs had little effect.
  • Angiogenesis is central process in tissue regeneration. The major value of embedding ASCs within the P-fibrin scaffolds was the bolstered neovascularisation observed at 7 days post-burn, which was significantly superior to the small increase observed with the P-fibrin only group. This would support the authors’ supplementary findings that suggest a role of the ASC secretome upregulating pro-angiogenic genes [5]. Although not fully studied, it is likely that the ASCs influence the population diversity of regenerative cells recruited to the burn wound to influence this superior angiogenic response.
  • To this end, there is some evidence in the present study to suggest that embedded ASCs can inflict a local tolerising pro-regenerative phenotype. Specifically, wounds treated with P-Fibrin embedded with ASCs showed a drastically greater coverage of the M2 immunosuppressive, pro-regenerative macrophages than when the wounds were treated with P-Fibrin gel alone.
  • It is encouraging that the wound thickness, collagen deposition and organisation between the studied hydrogel groups did not vary significantly, because this suggests that the hydrogels only accelerate but do not change the orchestrated sequence of the in-vivo regenerative response to full-thickness burns.
  • P-fibrin hydrogels hold great promise for burn wound healing applications, especially when conjugated with biological agents. Infection control is a crucial consideration in the burn wound healing process, and was not explored in the present study [5]. Interestingly, a recent study found that both infection control and neovascularisation post-burn can be enhanced through sequential delivery of P-fibrin embedded silver sulfadiazine loaded chitosan microspheres followed by P-fibrin embedded ASCs [6]. Future studies will likely focus on further characterising similar functional hydrogel constructs prior to progressing to more advanced trials.

References:

  1. World Health Organisation. 2018. Burns. Online: https://www.who.int/news-room/fact-sheets/detail/burns
  2. Janmey PA, Winer JP, Weisel JW. Fibrin gels and their clinical and bioengineering applications. J R Soc Interface. 2009;6(30):1-10.
  3. Overby RJ, Feldman DS. Influence of Poly (Ethylene Glycol) End Groups on Poly (Ethylene Glycol)-Albumin System Properties as a Potential Degradable Tissue Scaffold. Journal of Functional Biomaterials. 2019;10:1.
  4. Nam SY, Chung E, Suggs LJ, Emelianov SY. Combined ultrasound and photoacoustic imaging to noninvasively assess burn injury and selectively monitor a regenerative tissue-engineered construct. Tissue Eng Part C Methods. 2015;21(6):557-566.
  5. Chung E, Rybalko VY, Hsieh PL, Leal SL, Samano MA, Willauer AN, et al. Fibrin-based stem cell containing scaffold improves the dynamics of burn wound healing. Wound Repair Regen 2016;24:810–9.
  6. Banerjee J, Seetharaman S, Wrice NL, Christy RJ, Natesan S. Delivery of silver sulfadiazine and adipose derived stem cells using fibrin hydrogel improves infected burn wound regeneration. PLoS One. 2019;14(6):e0217965.

The Science of Human Sexuality

by Sesethu Mbunge

What better time, than the time of the release of the ever so controversial Lil Nas X’s music video for his single titled “Industry Baby”, to write about the neurobiology that underpins human sexuality? This masterpiece features an iconic shower scene, with a group of male bodies dancing in the nude, that had naysayers claiming that Lil Nas X is “turning people gay”. Contrary to popular belief, the nuance subject matter of gender identity and sexual orientation is not as simple as deciding to be gay. Although there is a huge gap in the understanding of the biological underpinnings of human sexuality, many studies have suggested that the prenatal environment, including the maternal immune environment as well as exposure to certain sex hormones, may play a role in gender identity and sexual orientation of the developing foetus. Further studies hypothesize that there is a genetic determinant of human sexuality, although these studies have been difficult to reproduce. It is believed that this resultant maternal, and potentially genetic, environment results in the organizational differentiation of the developing foetal brain. In simple terms, this means that these factors contribute to the structural differences in certain regions of the brain, and that these differences are what is attributed to the difference in the human sexual identity. The assumption with many of these studies was that sexuality is categorizable and binary. For the sake of cohesiveness, this summary will also be written under this assumption, although it is understood that sexuality is a spectrum.

Human sexual identity is categorized as gender identity and sexual orientation. Gender identity refers to one’s perception of oneself as male, female, or non-binary and this can be the same, or different from one’s biological sex. Sexual orientation refers to the pattern of emotional and/or sexual and romantic attractions to males, females, or both. To understand the effects of different factors on sexuality, let’s look at these factors individually.

Pre- and Perinatal Hormone Environment:

Animal studies have demonstrated that prenatal exposure to testosterone resulted in masculinization (male-type development) and that in the absence of testosterone feminization (female-type development) occurred. Masculinization results in permanent neural structural differentiation and occurs within the period when the brain is most sensitive to testosterone. Brain areas that are affected by testosterone levels are thought to be important for sexual differences in various adult behaviours including sexual behaviour, aggression, and cognition as well as gender identity and sexual orientation. Clinical studies have shown that in XY (typical male genotype) children that were born with ambiguous genitals developed into males when exposed to testosterone prenatally, but that if they had an androgen receptor (receptor for testosterone) mutation, they were phenotypically female and identified as female.

Studies in several animal models have shown that perinatal exposure to testosterone resulted in female partner preferences, whereas testosterone deprivation resulted in male partner preferences. In humans, it has been observed that women that were born with congenital adrenal hyperplasia (were exposed to an elevated amount of testosterone) developed masculinized genitals and behaviours and were less likely to be exclusively heterosexual in comparison to unaffected women.

Genetic Factors:

It is difficult to analyse the biological basis of gender identity in animal models, thus this is best studied in individuals that identify with a gender that is different from their biological sex. Although there is very limited evidence, it has been observed that in female-to-male transsexual individuals, there was a higher incidence of the A2 allele polymorphism for the gene that codes for a testosterone-synthesis catalysing enzyme, CYP17A1, compared to male-to-female transsexual individuals.

Familial and twin studies have shown that sexual orientation is moderately accounted for by a genetic component. A recent study approximated that about 40% and 20% of the variance in sexual orientation in men and women respectively was due to a genetic component. In a linkage study performed by Hamer in 1993, it was hypothesised that a locus, namely Xq28, on the X chromosome contained a gene that was loosely associated with homosexuality in men. This was then also confirmed in a larger genome-wide study, and it was also found that there were associations with chromosome 7 and 8. No specific genetic locus has been identified as associated with sexuality yet.

Neuroanatomy:

Studies have found that transgender individuals had structural and functional brain features that are more similar with individuals of the same gender identity, rather than with individuals with the same biological sex.

Rodent models have identified the sexually dimorphic preoptic nucleus (SDN) of the brain as the region associated with sexual partner preferences. In male rodents it was found that the larger the SDN was, the greater its attraction to female rats. It was also subsequently found that destruction of the SDN in male rats and ferrets either resulted in neutral or male preferences. This finding was also confirmed in sheep models, where they found that larger the ovine sexually dimorphic nuclei (oSDN) were associated with more female-oriented rams, whereas male-oriented rams had smaller oSDN. It was found that oSDN due to prenatal exposure to testosterone. Exposure of female lamb foetuses at the proper time was shown to alter oSDN size independently of genetic and phenotypic sex.

In humans, the third interstitial nucleus of the anterior hypothalamus (INAH3) has been implicated in sexuality. Based on its localization and the structure of its cytoskeleton, this nucleus resembles the oSDN of sheep. Studies have shown the INAH3 is smaller in homosexual men in comparison to heterosexual men, and the INAH3 in homosexual men is similar in size to that of women.

Maternal Immune Environment:

One interesting observation that has been made is the effect that the maternal immune environment has been shown to affect the sexual orientation of the developing foetus. It has been observed that homosexual men have, on average, more older brothers that heterosexual men. This is referred to as the fraternal birth order, and incidence of homosexuality increase by about 33% with each older brother. This is hypothesised to be due to the mother developing antibodies against a gene on the Y-chromosome that is a key factor in male brain development, and this immune response increases with each male pregnancy. This is subsequently thought to alter the neural structures that affect sexual orientation in boys that are conceived later. It was found that the mothers of homosexual sons that had many brothers, had a concentration of antibodies against neurolignin 4 (NLGN4Y), a gene that codes for a protein that is assumed to play a role in foetal brain development.

These factors are an indication that the events and environments that occur during early foetal development play a crucial role in determining the sexual identity of the developing foetus. Animal models have been found to display the causality of the effects of prenatal hormones on sexual orientation, but this however has not translated to gender identity. There are so many more biological processes that are implicated in sexual development that are yet to be understood or discovered. As such, it is biologically incorrect to reduce sexuality and sexual identity to a mere choice!

Reference:

Roselli, C., 2018. Neurobiology of gender identity and sexual orientation. Journal of Neuroendocrinology, 30(7).

Facts, some realistic heartbreak story, and an outrageous ending paragraph

by Sagel Kundieko 


At first, I thought it was a new virus that was practically wiping out the Chinese population. It was unrealistic that it would actually spread to the entire continent and cover all the many kilometres that there is to cover. Then we heard of Italy and the consequences of their stubbornness. Then finally it hit us too, in waves and lockdowns. It is really scary to think about how the economy has plummeted in this very short period of time. Also, how easily a virus from one corner of the world was easily able to cross barriers at such an overwhelming rate. On the other hand, the global pandemic aspect of it brings a sense of “we are all on this earth together” at the end of the day.  

The recent lootings and taxi violence is an offspring of the (increased) poverty, depression, and frustration from the lockdowns. It is clear that those most affected are from the black community because they have to commute to work and do not (literally) have pantries full of food or big companies that can make them money while they lockdown at home. This is not even considering that some do not have “homes” conducive for a lockdown or quarantine. Acknowledging that the lockdown was necessary, the inadequacy of the government in providing the necessary food to those who needed it, was problematic. 

On my immediate hand (usually written as on the other hand), the lockdown meant that I could not pursue my driver’s license because our documents needed to be renewed by the Home Affairs. In the grander scheme of things, that seems like a minimal issue, but the sense of unfulfillment still lingers, getting behind on an imaginary timeline I had set for myself. 

Furthermore, last year started off on a left foot (in the heat of the rising cases and lockdowns). I always felt that a problem is only a problem in relation to the other problems at hand. I imagined that something worse than my heartbreak would happen and I would forget about the man that broke my heart and move on, and it did. The idea of the possible end of the world or how insignificant and fragile our bodies are and how my life is worth nothing more than a statistic if I and those around me were to die, cured me of my heartbreak. A terrible parallel to draw between actual real world problems to a common heartbreak, it is unforgivable really. It is not even a parallel if you think of it, it is more of a mountain and me realising that because I am a pebble, then my problems must be a grain of sand, thus nothing to ponder ever so deeply on. I am more motivated now to do better, study harder, work harder, love God more, help those in need, go after my dreams and goals, and as I find true love, I experience it to the fullest of its capacities, because we do not know when another virus will head our way and who it will want to claim. I pray we survive through this as a world and do better for the future (do better in reference to the social class structures that have governed our countries, now we should realise that we are more the same than different and more together than apart).  

I also realise that the virus is the main topic at hand, but everything else that was wrong with the world before still exists. Even more so, humans are the deadliest virus this planet has ever been invaded by. That is an undeniable and uncontained fact.

A Whole New World

by Jesmika Singh

Am I really writing a piece about being in HONOURS? I still feel like I was just yesterday sending in applications for my first year of university. When they say university is over before you know it, they really weren’t joking. Regardless, it has been an exciting ride (even though parts of it have been stressful).

Throughout my schooling career and general social life, I have been someone that gets stressed very easily. I put a lot of pressure on myself to achieve my academic goals. Particularly in the third year of my undergraduate degree in 2020, I felt an even stronger need to push myself and put all my time and effort into my studies since everything was done through remote learning. As a result, the stress I felt during that year was unexplainable. Directly following that, I came into honours with the expectation that my stress would be even worse- I was moving to Cape Town from Durban; gaining more independence; being isolated from the majority of my loved ones and having to begin what I was told would be the hardest year of my university career. Granted, these things have been as challenging as expected, yet, I’m surprised to say that this has been one of the least stressful academic years I have had- perhaps I have gotten used to the stress or lost my ability to stress my usual amounts.

Honours is a year that I was told would push me to my breaking point- granted the year is far from over and there is still plenty of time left for that, somehow I have enjoyed the academic aspect of this year much more than any previous academic year. To be fair, if it were not for online learning, recorded lectures (I don’t know where I would be without these), teamwork and the lecturers, I doubt I would have been able to cope.

Something I have admired greatly about how this course has been run and kept my morale up- is how we are assessed. Unlike previous years, we were allowed (in some cases) to indicate the type of assessment we felt would best showcase our understanding of work and the way we were marked has been one of my favourite parts of the year. From the time I started school if your answer was not exactly what was in the memo, you didn’t get the mark- that was not the case this year. The lecturers took their time with each individual script/assignment to determine whether someone understood the work or not. If we didn’t get the correct answer but showed understanding, we could still do well. This kind of teaching and learning has helped me better understand my work, but more than that, it has helped me grow my confidence. If I had been marked like this for my entire schooling career, perhaps I wouldn’t have been so stressed and I may have been able to retain my work better. Being able to chase knowledge and understanding over answers from an unseen memo, has made a big difference in the way I take in knowledge.

I was also very fortunate to get a very helpful supervisor and co-supervisor this year. Without the constant guidance, kindness and willingness to assist from my co-supervisor, I don’t think I would have managed half of the challenges phased by my project and even the modules. By allowing me to ask questions at any time of the day and equipping me with the ability to solve problems I had myself, she has also assisted in helping me deal with the stress of Honours.

I am very grateful for being given this opportunity to do this incredible degree this year. I have made great friends, met highly accomplished academics, and opened doors for my career goals that I didn’t think possible.

If there was anything I would change about the way I handled this year, I would go into every assessment to aiming show my full understanding of topics rather than just putting down answers I thought were wanted.

To every individual that has helped me along my way through this Whole New World of Honours at UCT- Thank you!

CANCER RISK ESTIMATION USING COLONOSCOPIC SURVELLANCE AND MMR GENE MUTATIONS

by Kelly-Robyn Singh

Lynch syndrome is an autosomal dominantly inherited cancer syndrome which predisposes individuals to a wide range of cancers, most commonly, cancer of the colon and/or rectum (colorectal cancer- CRC). It presents as colonic adenomas (benign epithelial tissue tumor) at an early age of onset that is averagely seen in other cancers. Lynch syndrome is the most common type of hereditary colon cancer, and it is estimated that approximately 1 in every 300 people carry mutations which are associated with Lynch syndrome. These associated mutations are found in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 or PMS2. Consider the following analogy: the MMR genes encode the MMR machinery, which we can think of as the police-force of the genetic code, in the sense that they recognize inconsistencies in the genetic code which may have arisen during DNA synthesis, and they repair it to restore genetic stability, much like a policeman/woman would in the instance of crime. In a society without the police to maintain law and order, there would be chaos, much like there is when the mutated MMR genes cause non-functional MMR and subsequently, deleterious mutations are allowed to accumulate in the genetic code, uninterrupted.

The question is, could mutations in some of these mismatch repair genes have a more severe effect than others? Is colonic surveillance and removal of pre-cancerous adenomas an effective strategy to manage CRC risk and incidence? The paper by Møller et al. aims to investigate the effects of surveillance in individuals carrying Lynch Syndrome associated mutations and their risk of cancer in more effective and accurate estimates than the usual risk estimation approaches which mainly involve retrospective studies.

To accomplish this, a cohort of patients carrying mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2 were studied and monitored on an Oracle regional database, with the aim to correlate data across categories like age, sex and mutated gene as the data develops to identify significant trends.

The findings were that 314 patients had developed cancer out of 1942 mutation carriers with no prior history of cancer. The cancers were found were mostly CRC, followed by endometrial and ovarian. Interestingly, carriers with mutations in the MLH1 and MSH2 had an earlier age of onset (25 years) as compared to that of MSH6 and PMS2 carriers (40 years). The cumulative cancer incidence rates at 70 years (patient age)for each gene as well as ten-year crude survival can be found below.

Table 1: Cumulative cancer incidences for each MMR gene and ten-year crude survivals for their respective cancers

Figure 1: Cumulative incidences by age and mutated MMR gene for any cancer

These findings conclude that there are varied penetrance and expression patterns of each of the mismatch repair genes, with that of MLH1 and MSH2 being higher and therefore causing an earlier age of onset as well as incidence. The results of this paper conclude that colonoscopic surveillance did not significantly decrease the incidence of CRC, but it did result in a lower mortality rate. The early detection of pre-cancerous adenomas is therefore imperative to prevention and the prolonging of life.

References:

Møller P, Seppälä T, Bernstein I, Holinski-Feder E, Sala P, Evans DG, Lindblom A, Macrae F, Blanco I, Sijmons R, Jeffries J, Vasen H, Burn J, Nakken S, Hovig E, Rødland EA, Tharmaratnam K, de Vos Tot Nederveen Cappel WH, Hill J, Wijnen J, Green K, Lalloo F, Sunde L, Mints M, Bertario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Frayling IM, Plazzer JP, Pylvanainen K, Sampson JR, Capella G, Mecklin JP, Möslein G; Mallorca Group (http://mallorca-group.eu). Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2017 Mar;66(3):464-472. doi: 10.1136/gutjnl-2015-309675. Epub 2015 Dec 9. PMID: 26657901; PMCID: PMC5534760.

Are human personalities preprogrammed?

by Muhammad Adeeb Fakier

“The apple does not fall far from the tree”, is a common saying relating to offspring having a similar characteristic or quality to the parent. The advancement in genetic studies has allowed for the identification of genes associated with specific phenotypic observable characteristics, but what is the relationship between genetics and personalities?

Research from family, twin and adoption studies have indicated strong evidence for heritability of human personalities. However, the phenotypic architecture of the human personality is complex, and therefore includes uncertainty as either the same genetic networks may lead to different phenotypic outcomes; or different genetic networks in complex systems may lead to the same outcome. Past genome-wide association studies (GWAS) had very little success, where heritability of complex traits have been called “missing” or “hidden”.

The Temperament and Character Inventory (TCI) is a system that evaluates specific dimensions of personalities. TCI character traits have been identified to be associated with brain networks for metacognitive processes such as self-reflection and purposefulness; whereas temperament traits (innate traits) generate and condition automatic behaviors, such as stress reactions. Therefore focusing on self-regulatory character traits such as self-directedness, cooperativeness and self-transcendence can be used determine the health state of an individual’s adaptive functioning.

The study utilized a machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions. A discovery sample of 2149 individuals were used, and sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals were identified. Thereafter five cluster of individuals with distinct profiles were identified. Lastly the association significance of the SNP sets with one or more character profiles (resourceful, organized, creative, dependent and apathetic) were identified.

The GWAS analysis of the genotypic and phenotypic architecture of personality measured by the TCI, illustrated each SNP set maps to one or more genes, identifying its association to each of the five general character profiles (Figure 1). This was followed by categorizing the variation in health status of SNP sets as: well, ill and intermediate (Figure 2). It was found that 42 SNP sets identified to 727 gene loci were significantly associated with one or more of the character profiles. Interestingly the SNPs sets often had similar character profiles associated with particular molecular processes such as involved in regulation of inositol-calcium signaling for obtaining food (G_8_8) and for neuroprotection against injury (G_12_8).

In conclusion genetics have an influence on human personalities, and this study has illustrated that it is possible to characterize the complexity of genotypic and phenotypic architecture of self-regulatory character traits. The study highlighted that self-regulatory personality traits are strongly influenced by organized interactions among more than 700 genes, despite variable individual cultures and environments.

Reference

Zwir, I., Arnedo, J., Del-Val, C. et al. Uncovering the complex genetics of human character. Mol Psychiatry 25, 2295–2312 (2020). https://doi.org/10.1038/s41380-018-0263-6

Zwir, I., Mishra, P., Del-Val, C. et al. Uncovering the complex genetics of human personality: response from authors on the PGMRA Model. Mol Psychiatry 25, 2210–2213 (2020). https://doi.org/10.1038/s41380-019-0399-z

Into the Thick of it: Can Cannabinoids be used to treat COVID-19?

by Robyn Lesch

Weeding through fact and fiction in search of the truth

The therapeutic effects of cannabis have long been known because of the presence of cannabinoids like THC and CBD commonly used to treat various symptoms and side effects related to cancer – but what effect does cannabis have on COVID-19?

In recent years, with more research into its usefulness, cannabis has evolved from that substance your parents warned you about as a “gateway drug” into the shining flame at the end of a dark seemingly endless tunnel of research. As this research into the therapeutic properties of cannabis has developed, so has the mainstream use of cannabis products. These properties are mainly due to the presence of cannabinoids which refers to every chemical substance, regardless of structure or origin, that joins the cannabinoid receptors of the body and brain and that have similar effects to those produced by the Cannabis Sativa (C. Sativa) plant. With its remarkable healing potential, you may be wondering if cannabis could help fight the virus currently taking the world by storm – COVID-19. COVID-19 has resulted in millions of deaths, closed international borders, and has brought global economies to their knees. This contagious respiratory disease can leave one with a fever, feeling fatigued, and struggling to breathe and can very quickly become fatal. So, can cannabis help in the fight against COVID-19?

A January 2021 study published in the journal Aging has found that cannabis may offer some help for patients with COVID-19.

Cannabis and the cytokine storm

One of the main biological events that occur in patients with severe acute respiratory distress caused by COVID-19 is a “cytokine storm.” This is where the body experiences an extreme increase in proinflammatory cytokines. Cytokines are a category of proteins which are involved in the cytokine storm that leads to increased inflammation.

COVID-19 patients tend suffer from lung fibrosis, a dangerous and untreatable condition that leaves lung tissue scarred and making it difficult to breathe. If a substance could stop the cytokine storm, it would be able to suppress inflammation, prevent lung fibrosis, and possibly even put COVID-19 patients in remission.

The Experiment

Researchers used a well-established full thickness human 3D skin artificial EpiDermFTTM tissue model and exposed the tissues to UV in order to induce inflammation. The tissues were then treated with extracts of seven new cannabis cultivars. It was noted that out of seven studied extracts of novel C. sativa cultivars, three were the most effective, causing profound and concerted down-regulation of COX2, TNFα, IL-6, CCL2, and other cytokines and pathways related to inflammation and fibrosis. This data was further confirmed in the WI-38 lung fibroblast cell line model.

The Conclusion

In this study, C. Sativa, a type of cannabis, was found to reduce multiple cytokines and pathways related to inflammation and fibrosis. Two of these cytokines of note that were reduced were TNFα and IL-6, which are thought to be the main targets when trying to block a COVID-19 cytokine storm and acute respiratory distress syndrome.

Closing Thoughts

Cannabis has shown great potential in fighting against COVID-19, thanks largely to its anti-inflammatory properties. The study shows that cannabis could significantly improve the condition of COVID-19 patients by reducing a cytokine storm and protecting lung tissue from inflammatory damage. Novel anti-TNFα and anti-IL-6 cannabis extracts can be useful additions to the current anti-inflammatory regimens to treat COVID-19, as well as various rheumatological diseases and conditions.

Although this research is exciting and shows the potential power of cannabis in the fight against COVID-19, always remember to follow your doctor’s advice when managing COVID-19.

References

Kovalchuk, A., Wang, B., Li, D., Rodriguez-Juarez, R., Ilnytskyy, S., Kovalchuk, I. and Kovalchuk, O., 2021. Fighting the storm: could novel anti-TNFα and anti-IL-6 C. sativa cultivars tame cytokine storm in COVID-19?. Aging, 13(2), pp.1571-1590.

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