Monthly Archives: September 2021

Growing with change

by Emily Higgitt

At the end of my undergraduate degree in 2020, I made the exciting yet challenging decision to move universities and provinces to pursue my dream of studying neurosciences. When I reflect on this year, I see the many challenges I faced due to leaving home for the first time and the uncertainties of changing universities, but I also see all I have learned from this fantastic opportunity and all the lovely people I have met.

Leaving home and moving provinces was much harder than I thought it would be. I have lived in KwaZulu-Natal my whole life, so moving to Cape Town with little family and no friends was very daunting. Additionally, the COVID-19 restrictions limited my ability to meet new people, including my new classmates. Thankfully, I was able to meet my class and build connections and friendships with them all. I am grateful for the support we have provided each other during these difficult times of online learning.

Although, moving to a new province has also been a fantastic adventure. Cape Town is a beautiful province with so much excitement and activity. I have loved going on hikes on the mountain and walks along the beachfront.

Changing universities was a transition that challenged me the most this year. After working hard on my undergraduate degree, I was chosen to fill one of the spots in a highly competitive degree at one of the top universities in the country. Joining a university and a degree with such high status was overwhelming. I felt, and still feel, a lot of self-doubt and question if I am good enough to be here with all of these other outstanding students. However, as the months went on, I found that I am capable. Self-doubt still creeps in on me now and again, so I made little notes of positive affirmations to stick around my room. Now, whenever I feel anxious or doubt myself, I read those little notes to remind myself of all I have achieved thus far and that I am capable.

One of the most exciting adventures of this year has been conducting my research project. Joining a new lab and conducting experiments using fancy equipment is a big jump from the work of an undergraduate, but it makes me feel like a real scientist! After all the work and effort that I put in during my degree, it feels amazing to have come this far. I am very grateful for the support I have been given and everything I have learned from my incredible lab.

The most valuable lesson I have learned this year is the importance of giving time for myself and prioritizing my mental health. Unfortunately, academia does not always support mental health; therefore, life can become overwhelming and stressful very quickly. This year has taught me that my health and well-being are just as important as my marks. This year I have tried to develop a balance between my work and my health and happiness. Even if it’s taking a quick walk around the neighbourhood or sitting on the couch watching your favourite show. Taking time for yourself is just as important as doing that assignment because if your mind is weighed down, you cannot perform at your best. So, take a short rest and then get going again with a happy mind!

Learning and Growing

by Jessica Garlick

The build-up to honours was immense. Throughout my undergraduate degree, we would all speak about the plans we had for after our BSc and our ideal career path thereafter. Once third year rolled round and conditional acceptances were being given, there was an even greater pressure to succeed in our undergraduate degree and get our firm acceptances. We were constantly reminded (and reminding each other) that conditional acceptances can be revoked and the pressure built and built. Every postgraduate that crossed our paths was interrogated about their honours year- which course they did, what their project was, was it enjoyable, did they have any advice and what their plans going forward were. Most senior postgraduates would say that honours was their worst year and the most stressful year of their university career thus far. Which only built upon the daunting idea of the honours year. Then it happened, we got our firm acceptance emails which signified that our journey was only just beginning.

Most of us came to med campus on the first day of semester brimming with excitement and some fear- as to be expected with the years building up to finally being a postgraduate. The honours year so far, has been stressful, but enjoyable. There is a lot more freedom than being a undergraduate and I think this is the main reason previous postgraduates emphasised the difficulty of honours. If you are studying the right thing, then it really is enjoyable, but it is also very easy to fall behind if you don’t work consistently and efficiently. Time management is more important now than it ever has been and the covid-19 pandemic has only added to the importance of correct time management owing to more online-based learning.

In the clinical anatomy stream, dissections were not compulsory, but highly recommended. It became apparent that you definitely needed to attend the dissection sessions in order to pass the modules well and fully understand what was being taught. However, we no longer had demonstrators and lecturers holding our hands by telling us exactly what was expected and there was no longer the threat of not meeting DP to make us go to dissections. Luckily, I did not struggle to motivate myself to attend these sessions and thoroughly enjoyed learning while dissecting.  The fact that assessments are only held at the end of the modules (for my modules anyway) also made us believe we had all the time in the world to study…later. Time management is a must! Especially during the techniques module and subsequent academic modules.

Not only have we had to develop our time management skills even further, but our projects also give us a lot of freedom. However, each task (proposal, blog post/infographic, graphing assignment, literature review and data collection) need a lot of attention and cannot be done to a high enough standard last minute. Although rather cliché I am going to have to say; “with great power comes great responsibility”. The power in this sense is the furthering of our academic careers, the power of learning and gaining knowledge and skills that will benefit our future career and self-development. Choosing a project was a daunting task since many of us were unsure on what type of research would suit us and we had so many questions about the fields we had chosen. Luckily, there are helpful resources available to us when it comes to what the honours year is about and how to get to where we want to be.

We’ve had to learn to be flexible and adaptable as many have had to alter or adapt their projects- be it experimental design or overall topic. We’ve learnt that science isn’t about succeeding first time and often requires us to ‘play’ with our methodology and thinking processes. This is just part of being a scientist and not succeeding first time doesn’t mean you’ve failed, but rather that something needs to be adapted. This is part of the fun of science- even if it is stressful and time consuming. It will be worth it in the end and a lot of us are developing new skills while having to adapt our projects.

Lastly, those that are studying clinical anatomy or biological anthropology learnt to dissect cadavers and spent many hours dissecting, learning about and appreciating the human body- on a cellular, tissue, organ and system level.
Our first day with the cadavers was filled with excitement, but also a lot of trepidation. There is nothing that we could do to mentally prepare for the day we started dissecting and there was a lot of nervous energy in the cadaver room that day. However, after the first incisions were made, it became easier and our nervousness melted away into an eagerness to learn more.  Many of us named our cadavers since it felt disrespectful to simply refer to our groups’ cadaver as “the cadaver” or “the body”. Our group named our cadaver Gerry and naming him instantly allowed us to feel as though we were giving him the respect he deserved for donating his body for us to learn about anatomy and for research purposes. The cadavers didn’t only aid our understanding of anatomy, but also helped us to develop more empathy and respect for the living and dead.  I will always be grateful and remember what I learnt by dissecting Gerry as I continue my research in anatomy.

The honours year is full of curveballs owing to having to own up to our responsibilities and having to learn to be more independent in a lab or cadaver room and with our research in general. This is stressful and daunting for most of us, but I have already felt a shift in myself and I’m starting to feel like a scientist. I know we all have our undergraduate degrees telling us that we are now scientists, but there is a difference between being a scientist on paper and feeling or acting like a scientist. Slowly, my peers and I are developing skills that will help us on our journey as we specialise and fully delve into the world of research.

The neurovascular unit in retinopathy and neurodegenerative diseases

by Dane Sevenster

The prevalence of diabetes mellitus is on the rise globally, with Africa having an estimated increase of cases from 19 million to 47 million by 2045. Africa also has one of the highest percentages of undiagnosed cases with estimates that 60% of people are unaware they are living with diabetes. These predictions show the possible rise in economic and social costs facing Africa and the world as diabetes further grows into an epidemic.  

The increase in diabetes will in turn lead to a rise in one of the most common cause of blindness, diabetic retinopathy, especially in the population who are unaware of their condition and allow the disease to progress. Diabetic Retinopathy (DR) is one of the most common complications of diabetes and requires further investigation of the components and mechanisms that lead to early progression of the disease.  One such area that has received more attention has led to a great change in the understanding of the disease.  

The shift was in the focus on retinopathy as a solely microvascular disease into a combined neurodegenerative and microvascular disease. The review article of mention discusses the role of microvascular abnormalities and neurodegeneration in the pathogenesis of diabetic retinopathy, dementia and possibly other neurodegenerative diseases. The term neurovascular unit (NVU) arises often, which refers to the functional coupling and interdependency of neurons, glia and the highly specialized vasculature in the central nervous system (CNS). This NVU occurs within the retina of the eye and brain, forming a core component of the blood brain barrier to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. These cells maintain an intimate connection and are often the first to respond to inflammatory effects such as cell damage or pathogen invasion, sending subsequent signals to nearby cells that could disrupt the fine balance between pro- and anti-inflammatory pathways.  

Evidence shows that neurodegeneration via this NVU and its inflammatory response is an early event in the pathogenesis of diabetic retinopathy and other neurodegenerative diseases that could be linked to the development of microvascular abnormalities. The review states that the study of the underlying mechanisms leading to early disruption of the NVU, and later neurodegeneration is essential for the development of new therapeutic strategies. The below figure summarizes the potential mechanisms linking retinal neurodegeneration and early microvascular impairment, highlighting that impaired cell signaling within the neurovascular unit as a critical stage of early pathogenesis.   

What reveals the greatest evidence of the implications of the neurovascular unit and its future study is the idea that brain neurodegeneration as seen in Alzheimer’s may simultaneously occur with retinal neurodegeneration. Seeing as how many pathways such as insulin signalling impairment, low-grade inflammation, the accumulation of advanced glycation end-products (AGEs) and an increase in oxidative stress are replicated within both Alzheimer’s disease and retinopathy. This calls for investigation into the interdependence of these NVU components within the brain and retina, the relative contribution of each component, as well as the specifics of phenotypic or morphological changes that occur in the different cell types of the NVU to better explain the early progression of diabetic retinopathy, neurovascular and neurodegenerative diseases and hopefully provide insight into better therapies.  

The scope of research into these diseases has changed and grown over the years and the insights that can be gained from the NVU are promising, especially in the field of development of vaso- and neuroprotection therapies. 

References

  • Simó, R., Stitt, A. W. and Gardner, T. W. (2018) Neurodegeneration in diabetic retinopathy: does it really matter?, Diabetologia, Diabetologia, 61(9), pp. 1902–1912, [online] Available from: https://dx.doi.org/10.1007/s00125-018-4692-1. 
  • Gorelick, P. B., Furie, K. L., Iadecola, C., Smith, E. E., Waddy, S. P., Lloyd-Jones, D. M., Bae, H.-J., Bauman, M. A., Dichgans, M., Duncan, P. W., Girgus, M., Howard, V. J., Lazar, R. M., Seshadri, S., Testai, F. D., Van Gaal, S., Yaffe, K., Wasiak, H. and Zerna, C. (2017) Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association, Stroke, Stroke, 48(10), p. . 
  • Flaxman, S. R., Bourne, R. R. A., Resnikoff, S., Ackland, P., Braithwaite, T., Cicinelli, M. V., Das, A., Jonas, J. B., Keeffe, J., Kempen, J. H., Leasher, J., Limburg, H., Naidoo, K., Pesudovs, K., Silvester, A., Stevens, G. A., Tahhan, N., Wong, T. Y., Taylor, H. R., Bourne, R., Ackland, P., Arditi, A., Barkana, Y., Bozkurt, B., Braithwaite, T., Bron, A., Budenz, D., Cai, F., Casson, R., Chakravarthy, U., Choi, J., Cicinelli, M. V., Congdon, N., Dana, R., Dandona, R., Dandona, L., Das, A., Dekaris, I., Del Monte, M., Deva, J., Dreer, L., Ellwein, L., Frazier, M., Frick, K., Friedman, D., Furtado, J., Gao, H., Gazzard, G., George, R., Gichuhi, S., Gonzalez, V., Hammond, B., Hartnett, M. E., He, M., Hejtmancik, J., Hirai, F., Huang, J., Ingram, A., Javitt, J., Jonas, J., Joslin, C., Keeffe, J., Kempen, J., Khairallah, M., Khanna, R., Kim, J., Lambrou, G., Lansingh, V. C., Lanzetta, P., Leasher, J., Lim, J., Limburg, H., Mansouri, K., Mathew, A., Morse, A., Munoz, B., Musch, D., Naidoo, K., Nangia, V., Palaiou, M., Parodi, M. B., Pena, F. Y., Pesudovs, K., Peto, T., Quigley, H., Raju, M., Ramulu, P., Rankin, Z., Resnikoff, S., Reza, D., Robin, A., Rossetti, L., Saaddine, J., Sandar, M., Serle, J., Shen, T., Shetty, R., Sieving, P., Silva, J. C., Silvester, A., Sitorus, R. S., Stambolian, D., Stevens, G., Taylor, H., Tejedor, J., Tielsch, J., Tsilimbaris, M., Van Meurs, J., Varma, R., Virgili, G., Wang, Y. X., Wang, N.-L., West, S., Wiedemann, P., Wong, T., Wormald, R. and Zheng, Y. (2017) Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis, The Lancet Global Health, The Lancet Global Health, 5(12), pp. e1221–e1234. 

Life in a year

by Leoné Pretorius

Even though the year 2021 and its academic activities have not yet come to an end, I think most of us will agree that the first part of this academic year has been filled with a lot of events and challenges that it has felt that we have experienced a whole year within six months. At least that is how I have experienced it…

With a rocky start to commence my studies in February, within the BMedSc Applied Anatomy honours stream, I was still optimistic for the academic year ahead and was prepared to use every opportunity given to me to make a success. I was given the opportunity to have contact classes and dissections for the first part of my General Techniques, Modules 1 and 2 courses.

It has been a real privilege and thrill to be able to interact with other students in my stream and from other streams that dissected or had a class with us (The Biomedical Engineering Master students and the Neuroscience honours stream). Having this opportunity to interact proved beneficial with relaying and solidifying my knowledge in the field together with working up close with my study material.

I had the experience to dissect properly following the relevant study block and it proved immensely beneficial while studying and recalling what I had seen, while I had traced and searched for certain structures. All in all, I was very intrigued by my learning environment and how I was growing throughout it. Unfortunately, as I mentioned, some events would hinder or disrupt these opportunities, and some weeks we would have to resort to online learning. The transition was smooth but commencing contact classes thereafter would prove challenging in the beginning.

Coming from a different university, where I had completed my undergrad, then adapting to UCT (a new setting, lifestyle, and academic activities) has been challenging here and there but also beneficial. Despite some technical difficulties faced with my transition, I must admit that the kindness and support in this environment (with regards to my well-being) is not something I am used to, and I am grateful to my peers and academic team for this experience.

Contact classes, although in my experience, can be very interactive and beneficial can also prove to be very draining, and commencing my Modules 3 and 4 stream was a blissful break in the form of an online platform. Although, being cooped up after 6 weeks, I wanted to go back to class again.

Finishing all my tests, assignments, and exams during this first part was stressful and I have doubted myself more than once, but the assistance and aid given to me was nothing but reassuring. Looking back at all that I have accomplished or overcome, even in this week with 3 exams, my SciComm Infographic, and this reflective piece, I truly am amazed.

For the future and maybe even for prospective students in this field, I would not be able to give an analogy of how I would do things differently and more readily to ensure a successful academic year. Because, as the year 2020 and 2021 has proven to us, no matter how prepared you are or you think you are anything can happen at any time and although being able to adapt is a good trait to have, it is also okay if you struggle at first or do not have the right approach at hand. If anything, I would just like to remind myself and others to always be kind to yourself, the rest will follow.

It’s a Beautiful Life

by Kate Morris

Being a fairly anxious person, I was a ball of nerves as the start of my honours
year loomed closer and closer. Would I cope with the workload? Am I cut out
to deal with the stress of postgraduate life? Will I manage to adapt to the
transition and bid farewell to my days as an undergraduate student? According
to most opinions imparted on me regarding postgraduate life, all of those
questions were met in my head with a resounding no.
And how pleasantly surprised I have been. Don’t get me wrong, being an
honours student ain’t easy, but to say I have loved my first semester of my
course in neuroscience & physiology would be a serious understatement. I
have had the opportunity to be taught by lecturers who are intelligent and
inspiring, to explore a whole new campus, experience life at a different
university, and to witness the bond that has formed between the 12 students
of my honours stream. I have found the content that we have covered so
invigorating and have very much appreciated the time I have managed to
spend in the lab – along with the additional skills I have acquired. And while
the prospect of taking on an experiment that will result in the writing of my
first thesis in the next few months is rather frightening, it is also absolutely
amazing. Second semester, bring it on!
Of course, the deadlines, the workload, the amount that we are sometimes
required to juggle at one point in time is challenging. Since I was expecting to
never have any time for myself and to be constantly drowning in work, as
often was the case in undergrad, I have found it difficult at times to adjust to
the workload and way of learning in postgrad – let along take some much needed rest! The situation in the world at the moment resulting in
predominantly online learning does not help this, and towards the end of this
semester I have found myself feeling particularly burnt out.
However, I have to say that the support and guidance I have received from all
levels of the academic hierarchy – be it masters/PhD/post-doc students,
lecturers, or medical doctors – has been outstanding. While there were
elements of this in my undergraduate days, the sheer minuteness of our
honours classes and the structure of postgrad in general has allowed for the
support to be more pronounced for me. When asked what the best things
have been about my honours year, the atmosphere of postgrad and the feeling
that there are so many people around you who are rooted in your success is
definitely at the top of my list.
I wait in anticipation for what this next semester will bring, and the journey
that this year will send me on. I am so grateful to be given this opportunity to
study what I love in a time when science is once again proving itself immensely
and is at the forefront of so many aspects of our lives today. I am proud of the
field I chose to study in, and I am proud of where I am today. It’s been a
beautiful year, it’s a beautiful life.

Antigen-specific T-cell Activation Distinguishes between Recent and Remote Tuberculosis infection

by Samar Abrahams

Introduction:

Mycobacterium Tuberculosis (Mtb) remains the number one killer in South Africa, with insufficient diagnostics and treatment contributing to the high mortality rates. With limited resources and the number of deaths reaching 58,000 individuals in 2019, it is imperative that all cases are detected, and that treatment is allocated to those most at risk of active Tb disease (ATB).

In this study the authors aimed to identify a blood-based biomarker that can be used in a simplified assay to measure risk of progression to active TB disease (ATB) and that can classify different stages of TB infection (TBI) that confer an increased risk of ATB-progression.

TB thrives in poverty-stricken areas where resources are limited. Thus, this study addresses a very important issue as it will allow for the identification of Mtb-infected individuals who are likely to progress to ATB (TB-progressors) and thus permits the prioritization of TB-preventative therapy (TPT) to this high-risk cohort.

Furthermore, none of the currently available TB diagnostic tests can detect TBI individuals that are likely to progress to ATB as the tests are unable to differentiate between recent infection (likely to progress to ATB) and persistent infection (low risk of progression). In addition, the identification of a blood-based biomarker presents an appealing alternative to traditional sputum-based tests.

In this study the authors focused on the expression of the T cell activation marker, HLA-DR, on Mtb-specific T cells and its potential as a blood-based biomarker. The authors hypothesized that more recent TB-infection would yield higher levels of activated Mtb-specific T cells compared to that of remote TBI and thus there would be increased expression of HLA-DR during recent infection which would signify increased risk of ATB-progression.

Methods:

Adolescents and adults were recruited for the study and divided into groups according to the following table:

Peripheral blood mononuclear cells samples were collected from the participants, stimulated, stained, and analyzed using flow cytometry. ∆HLA-DR Medium fluorescent intensity (MFI) was then measured for the test cohort and TB progressor cohort in a blinded and unblinded analysis, respectively.

Results & Conclusion:

Results generated from the test cohort revealed that HLA-DR expression on Mtb-specific CD4+ T cells, was able to effectively differentiate between those with recent QuantiFERON-TB positive (QFN+) conversion and persistent QFT+ individuals as well as persistent infection and recently diagnosed ATB. Furthermore, results from the TB-progressor cohort revealed that HLA-DR expression was also able to distinguish which TBI infected individuals were likely TB-progressors or non-progressors, with HLA-DR expression on Mtb-specific T cells being upregulated in likely TB-progressors and recent Mtb-infection.

From these results it can be deduced that HLA-DR expression on Mtb-specific CD4+ T cells is a promising biomarker candidate that can be measured and used as a screening test to identify individuals with recent infection and likely TB-progressors, thus enabling the allocation of TPT to this high-risk cohort. Provision of TPT to likely TB-progressors, is essential in middle to low-income areas where TB is endemic and thus distribution of TPT to all TB-exposed individuals is not feasible.

Furthermore, given that HLA-DR is a blood-based biomarker, it presents with an easily accessible and readily available sample. Thus, such a blood-based test can be applied to a broader category of TB-patients, such as those with extra pulmonary TB for which sputum-based tests are not applicable.

The use of HLA-DR MFI biomarker as a screening test can be combined with further clinical investigations to prioritize TPT with the goal of mitigating the TB burden in resource limited areas.

Notes to the reader:  

  1. QuantiFERON-TB is a test that measures IFN-y which is a cytokine produced by sensitized T cells in response to Mtb-antigen exposure. When a patient has a persisting QFN+ test it is an indication of persistent infection. 
  2. HLA-DR is an MHC class 2 molecule expressed on the cell surface and is involved in antigen presentation to elicit an immune response. HLA-DR is also expressed by CD4+ T helper cells and in this case, it serves as a correlate of T cell activation.

References:

  1. Mpande, C., Musvosvi, M., Rozot, V., Mosito, B., Reid, T., Schreuder, C., Lloyd, T., Bilek, N., Huang, H., Obermoser, G., Davis, M., Ruhwald, M., Hatherill, M., Scriba, T., Nemes, E., Mahomed, H., Hanekom, W., Kafaar, F., Workman, L., Mulenga, H., Ehrlich, R., Erasmus, M., Abrahams, D., Hawkridge, A., Hughes, E., Moyo, S., Gelderbloem, S., Tameris, M., Geldenhuys, H. and Hussey, G., 2021. Antigen-Specific T-Cell Activation Distinguishes between Recent and Remote Tuberculosis Infection. American Journal of Respiratory and Critical Care Medicine, 203(12), pp.1556-1565.

The Refuse Removal System of the Sleeping Brain

by Kate Morris

Sleep. We all need it, yet few of us get enough of it. Now more than ever before the importance of sleep in protecting and prolonging the health of the brain is evident. With neurodegenerative diseases being among the most prevalent in the world today, maintaining cognitive function throughout an individual’s life in the hope of escaping neurological decline is a prominent focus of scientific research. The build-up of neurotoxic waste, such as the protein amyloid beta, in the brain is a major factor in the development of these disorders. Therefore, the recent discovery of a system that can clean the brain more efficiently during sleep, the glymphatic system, was pivotal. Reviewed by Hauglund, Pavan &
Nedergaard (2020), crucial factors influencing this system – which has been referred to as a garbage truck within the brain (Nedergaard, 2013) – are identified and compared, illustrating the biological necessity of sleep and optimal glymphatic clearance in warding off neurodegenerative disease.

Original research by Xie et al. (2013) observed the flow of CSF into the brain in live mice using powerful microscopy. Hablitz et al. and Winer et al. then studied the impact of brain waves during sleep and wakefulness on glymphatic flux and on amyloid beta levels in the brain, respectively. Finally, microscopic analysis was done by Mestre et al. (2018) on the movement of a fluorescent marker in the CSF of mice with and without distinct perivascular AQP4 channel expression. These channels are little filters that are crucial for allowing adequate flow of CSF into brain tissue.

Greater glymphatic ‘flushing’ of the brain was found to occur during sleep owing to brain wave activity and hormone levels characteristic of this state (Figure 1). Brain wave activity characteristic of wakefulness in turn foresaw higher levels of amyloid beta in the brain, correlating with poor sleep quality – which reciprocally affects amyloid beta levels. Additionally, mice lacking distinct perivascular AQP4 expression experienced a reduction in glymphatic clearance (Figure 2).

These results emphasize the importance of sleep and the quality thereof in
maintaining efficient glymphatic clearance of the ‘garbage’ in the brain,
and preserving cognitive function throughout one’s life. With 25 to 60% of
patients with neurodegenerative disorders such as Alzheimer’s Disease
experiencing dysfunctional sleep, future research on means to increase glymphatic clearance will be indispensable to the continuing fight against cognitive decline.

References

  1. Hauglund, N., Pavan, C. & Nedergaard, M. 2020. Cleaning the sleeping brain – the potential restorative function of the glymphatic system. Current Opinion in Physiology, 15: 1-6.
  2. Mestre, H. et al. 2018. Aquaporin-4-dependent glymphatic solute transport in the rodent brain. eLife, 7: e40070.
  3. Nedergaard, M. 2013. Garbage truck of the brain. Science, 340: 1529-1530.
  4. Xie, L. et al. 2013. Sleep drives metabolite clearance from the adult brain. Science, 342:373-377.
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