scientific communication – ⋆ Second Gen Desi ⋆

Reading Time: 7 minutes

As a scientist with two years after her PhD training complete, I’ve realized time and time again the importance of effective scientific communication. I find value in reviewing the work of fellow colleagues and presenting it to an audience who has yet to be introduced to new findings.

I’ve mentioned before in previous “science-based” posts on this blog that science shouldn’t be intimidating, but oftentimes it comes across that way because many scientists are used to speaking with their peers. After years and years of school, training, and specialized research, technical terms become a part of one’s everyday jargon in the scientific research field.

So when I see scientific communicators like Bill Bryson—or in this post’s case, Dr. Sarah McKay—publish works meant for a general audience, I’m enthusiastic about reading them from a critical scientist’s point of view, and featuring them on this blog to pique your interest.

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The reason McKay’s book, The Women’s Brain Book, came across my (virtual) desk was because a fellow woman in STEM, Dr. Anjali Kasunich, and I connected on Instagram to form a “nerdy science girls” book club of sorts, because of our shared passion for disseminating topics in science for the general public. Anjali and I both thought TWBB would be a fascinating read for our inaugural IG Live book club series since it was expected to contain a hefty collection of peer-reviewed studies, simmered down to simplicity, in relation to a woman’s hormonal health and her brain.

TWBB has a chronological order to its chapters, with the book spanning over how a woman’s brain is formed, conditioned, influenced, and changed throughout all of life’s stages. Major external factors like the environment in which we grow up in, and the social connections we make, have a crucial impact on our general brain health as well.

Depending on your level of interest in a specific life stage and how it affects the woman’s brain, it’s easy to jump from one section to the other in the book without feeling incredibly lost. I decided to read the book in the “traditional” way, and while my background as a scientist made me familiar with some of the studies and concepts Dr. McKay mentions throughout the book, I found at least four key takeaways from the book that I thought were worth mentioning:

1. We are to be female, unless SRY has its way

My sub-heading title is not to be taken literally, but it refers to some interesting observations…

In the very first chapter of TWBB, McKay addresses an important detail – female brain development technically doesn’t take place right at conception, and its progression is based on whether or not the Y chromosome is present. If we define (in this context) a biological female as having two X chromosomes, and a biological male as having one X and Y chromosome, we can then understand why the presence of these chromosomes is life-changing.

McKay notes that when XY embryos are 6-8 weeks old, a gene known as the “sex-determining region of the Y chromosome” (SRY) is turned on. SRY allows for the development of the testes, as well as turns on several more genes that guide in other “male-associated” biological processes. Without the Y chromosome however, SRY and it’s associated genes remain off, and we become female!

I would have thought that if SRY has such a powerful role in male development, a similar gene would have a role in females, but that is not the case. I also found it interesting that while the presence of androgens (the family of male hormones that includes testosterone) turns on genes that involve the development of male organs and physical characteristics, the female hormone estrogen doesn’t have such a role in “feminization”. In fact, ovaries develop in the absence of testosterone.

We are conditioned to think that if A=Male, then B=Female, but perhaps we should think of it more like 0+A=Male and 0=Female. Nature prefers us to be female unless otherwise noted 😜.

2. Nature and nurture are equally important in brain development

Growing up in California, I remember seeing ads on TV—and later billboards, buses, and the metro when I moved to Los Angeles for grad school—for the First 5 California campaign, which emphasizes the importance of the first five years in a child’s life in regards to cognitive, physical, and emotional development.

In TWBB, McKay provides examples for which natural disasters could impact this development. One such example was an event that took place in Montreal in the late 90s. An ice storm left the city without power for 45 days, and researchers took it upon themselves to monitor women who were pregnant at that time to see how the development of their children was affected for years to come.

Understandably, the “Project Ice Storm” babies were born prematurely, and this also correlated to timing of a woman’s pregnancy (very early and very late stage pregnant women tended to have premature births). When the babies became toddlers, they not only had cognitive and language developmental delays, but attention deficits and behavioral problems as well. “Ice Storm Girls” had increased risk of puberty, obesity, and asthma, but interestingly, “Ice Storm Boys” tended to have more serious problems compared to the girls, and researchers hypothesize that this may be due to the fact that the female placenta is a more protective barrier against maternal stress hormones. While we can’t control the presence and timing of natural disasters, this study seems to demonstrate that external factors that impact a pregnant woman’s well-being can lead to striking outcomes in the development of her unborn children…

3. Hormone sensitivity and depression

I have struggled with depression as early as 18, but over the years, I have noticed that while it may be underlyingly chronic, there are certain periods in my life when the condition feels “stronger” than others. If I am to line up all the variables that could be involved, I automatically consider external factors contributing to stress, hormone fluctuations, and diet (quality and quantity of food, in addition to vitamin supplementation).

So I was certainly interested to see what sources McKay collected in regards to premenstural syndrome/ premenstrual dysphoric disorder, or PMS/PMDD. I am highly convinced that during a very stressful period of my life in late 2018 (the fourth year of my PhD, prior to the publication of my first paper…you can imagine), I was suffering from all symptoms associated with PMDD.

Some researchers have suggested that PMS is something that has developed out of social context, meant to “put down the woman” as a reason for her “inability” to perform activities. At first, I wasn’t sure how I felt about this because the way I see it, it is good to have a medical reason to explain why you feel certain symptoms at certain times of the month. Of course, each woman has a unique experience—unique symptoms, unique timings, you name it. I often found that in my situation, I had non-stop irritability, mood swings, intense bouts of crying, and physical issues like fatigue, sleepiness, and bloating that went on for half the month, only to quiet down around my period, but rise back up again within a few days after my period ended.

So, I did have these crazy symptoms, but sometimes it felt like I was under nature’s wrath for almost the entire month, or sometimes only in the two weeks before and after my period. Confusing in an understatement 🤷🏽‍♀️.

McKay’s note about a 2013 Canadian study titled “Mood in Daily Life (MiDL)” was able to find that in a cohort of women who were asked about their PMS-associated symptoms—without knowing they were being asked about PMS—there was no significant correlation that PMS phase influenced mood. The researchers suggested that the symptoms were more influenced by factors in a woman’s life that were external, like lack of social support, environmental stress, or poor health.

While this could be, I was relieved to see McKay included a note by Jayashri Kulkarni, a researcher who supports the study of endocrinology to understand what causes PMS. And when she said that “women may differ in their sensitivity to hormones, perhaps via genetic variations in receptor structure or number”, I wanted to stand up and scream RIGHT???? THANK YOU 😂! I’m sure some kind of specialized hormone profiling for women at different phases of their menstural cycle could bring SO much more insight into caring for unique sets of symptoms. And given that my family does have a (maternal) history of mental illness, I can’t help but hypothesize that my genetic make-up influences how reactive I am to the hormones in my body, and how that in turn can influence how I feel.

4. Estrogen’s importance in late life

Even though estrogen doesn’t seem to be “so important” in utero, we can see it has tremendous effects on our well-being as we get older. McKay noted several points about estrogen throughout the book, including the point that high levels of the hormone in young, fertile women are thought to lower schizophrenia risk (although, context is needed to clarify what is considered “high”), and that low levels of estrogen could exacerbate PMDD.

In the latter half of the book, McKay touches upon menopause, and how estrogen and glucose are essential players in menopausal outcomes. The brain’s main fuel source is glucose, and it is a greedy little organ consuming 20% of our resting metabolic rate (RMR). McKay mentions an interesting observation that women who’ve had their ovaries removed before menopause experience a critical drop in estrogen, and that this drop is associated with increased type 2 diabetes risk. This risk is similar in women after they experience menopause naturally, suggesting that estrogen may have an essential role in regulating glucose metabolism and lowering diabetes risk.

While we can’t fight nature on certain processes like menopause (although solutions like hormone replacement therapy are available, with McKay going into detail on that in the book as well), it’s eye-opening to see how such tiny molecules have an incredible impact on our metabolic processes and in turn, our physical outcomes and well-being. All the more reason to take care of ourselves as much as possible!

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McKay has done an incredible job compiling what is known about the field in regards to women’s health and the brain, but as she points out time and time again, there is still so much more that can be done to understand a woman’s biology and its impacts on her brain health.

Recently, the NIH and other research funding bodies have stressed the importance of including male and female subjects in future research projects—especially if you have any hope of wanting to have your research funded in the future. This is a great step in the right direction, but there is no doubt we have a lot of catching up to do, as well as needing to put in energy to shift the current social construct of how women’s health is perceived.

If you’ve ever been curious about what we know so far about women’s health and the brain, TWBB is certainly a resource for anyone in this regard, whether you have an extensive science background or not!

Reading Time: 6 minutes

This is a blog post aimed to make technical scientific concepts more “digestible” for a lay audience. The work discussed is based on the research by Kusnadi et al., published in Science Immunology in January 2021. To read their work directly, please click here.

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It’s been over a year since the words lockdown, remote working, and stay-at-home became frequent in our conversations, and we have the global impact of the COVID-19 pandemic to thank for that.

Since then, we have applauded the efforts of fast-acting scientists and pharma in pumping out effective vaccines to help slow down transmission, but unfortunately, vaccine administration efforts have been inconsistent all over the world. Global herd immunity seems like a noble concept, but with conflicting policies and lack of organization among governments, it’s something that will be impossible to reach—at least in the short-term.

But those of us who have been vaccinated are incredibly lucky. Vaccines introduce biological material (based on an infectious agent) into the body to prompt a response from the immune system. If a vaccinated individual encounters the actual infectious agent in the future, their immune system should be able to recognize the foreign invader and prevent an infection from progressing. And of all the immune system’s key players, we have our lymphocytes—our T cells—to thank for this!

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In a previous blog post of mine, I described in general what CD8+ T cells are, but let’s recap:

T cells are born in the thymus (hence the “T” in their name) and primarily serve as “soldiers of the body”. If the body is under attack by foreign particles (often referred to as antigen), T cells are the main players in fighting off these particles to prevent damage in the body.

They are further categorized as “T helper” cells (CD4+) or “cytotoxic T” cells (CD8+). CD4 and CD8 are structures made out of carbohydrate and protein “blocks” and exist on the surface of T cells, giving off their identity. CD4+ and CD8+ T cells differ in how they interact with other cells in the immune system and foreign invaders.

So we know that vaccines can provide protection against viral infections like COVID-19 by introducing T cells to parts of a virus and priming them to recognize the virus in the future. But for those who were infected with COVID-19 directly, did the intensity of the symptoms they experienced alter their immune system at the cellular level?

A collaborative group of scientists out of San Diego, California and the United Kingdom believe this was something worth investigating, and went so far as to use advanced genetic sequencing techniques to conclude that when it comes to our immune system warriors—CD8+ T cells—the severity of COVID-19 symptoms could affect how these cells look and function. Their work was recently published in Science Immunology, a prestigious peer-reviewed journal in the immunology field.

Article by Kusnadi et al. recently published in *Science Immunology*

Since CD8+ T cells are critical when it comes to vaccine effectiveness and understanding immunity, it would make sense to characterize how CD8+ T cells are affected by COVID-19 infection. Obviously at the time this study began, not much was known regarding this, or much about COVID-19 in general.

The authors used blood samples from healthy donors, COVID-19 patients that were not hospitalized (characterized as ‘mild disease’ patients), and those that were hospitalized (‘severe’ patients) to isolate peripheral blood mononuclear cells (PBMCs).

PBMCs hold the key players of the immune system—T cells, B cells, natural killer (NK) cells, and monocytes—and are characterized by their round nuclei. Isolating this layer from the peripheral blood makes it easier to analyze CD8+ T cells in particular.

To isolate CD8+ T cells from the PBMC samples of COVID-19 virus-affected patients, the authors used a “cell sorter” to specifically collect CD8+ T cells expressing CD137 and CD69. Both of these markers indicate CD8+ memory T cells that are activated and are ready for battle. Going back to my earlier post, tacking the word ‘memory‘ next to CD8+ T cells indicates that these cells have the ability to recognize and act against a foreign invader.

Interestingly, the expression of CD137 and CD69 was increased in CD8+ memory T cells derived from “severe” COVID-19 patients compared to “mild” COVID-19 patients, perhaps indicating that severe patients could have an increased protective response to COVID-19 antigens in a future encounter.

A very basic and cartoonish depiction of activated CD8+ memory T cells in mild and severe COVID-19 patients.

Even though the analysis becomes more complex as the paper continues (given the nature of genetics-based techniques), there is no need to feel intimidated. There are still key take-aways from the paper that even someone with a non-scientific background would appreciate.

Depending on the viral infection, CD8+ memory T cells can respond by activating a number of different genes that can help with fighting back at the infection. For example, COVID-19-reactive CD8+ memory T cells were observed to express genes associated with exhaustion, the production of molecules (cytokines) that assist with fighting off infections, and activating T cells.

“T cell exhaustion” is exactly what it says—when T cells lose their ability to fight off infections due to non-stop stimulation by a foreign invader, they tire out and do not function optimally in their normal defensive roles. A common marker of “exhaustion” is programmed cell death protein (PD-1) which T cells can express on their surface. The issue is that PD-1 is also involved in the activation of T cells, so like most things in biology, it’s not black and white—there needs to be a balance.

The authors knowing this utilized single cell transcriptomics, a process that allows us to examine all sorts of genes expressed by an individual cell, to see if there was more to characterizing exhausted T cells beyond what is seen at the surface level.

Ultimately, they found that CD8+ memory T cells reactive to COVID-19 expressed a number of genes associated with exhaustion, because of their connection to type 1 interferon signaling. This cell signaling pathway is associated with immune system regulation and has been noted by earlier studies to be linked to the development of exhaustion in T cells.

A simplified version of a “cluster map” and a “heat map”. More advanced depictions of these plots can be used to assess how genes group together in a particular sample and if they share similar functions.

Although patients with mild disease had more exhausted CD8+ memory T cells compared to severe disease patients, the exhausted CD8+ memory T cells in severe patients showed an increase in the number of genes associated with toxicity and inflammation.

Even though we would see this as a “negative” attribute of severe infection, it was noted that those with severe disease had CD8+ memory T cells that could survive for a longer time, although whether this observation can provide long-term immunity still requires investigation.

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Given that this is a study involving live individuals, using PBMCs is the only way to go, even though the analysis can be limiting (we can’t exactly do lung biopsies willy-nilly!). Even with its limitations however, the overall study does bring valuable insight as to how CD8+ T cells are affected by mild vs. severe COVID-19 infection.

The authors were able to use techniques to isolate single CD8+ T cells reactive to COVID-19 and determine that although patients with mild disease have more CD8+ T cells that are exhausted, the exhausted CD8+ T cells that severe patients do have lean towards higher levels of toxicity and inflammation, despite these cells also exhibiting features of increased memory responses and survival…

Maybe in this case, quality does take precedence over quantity? It will be interesting to see if any follow-up studies are conducted based on the findings of this paper, as we still have so much to learn about COVID-19. Although I do think it’s safe to say the authors uncovered some interesting details on how COVID-19 infections impact our immune system’s essential soldiers.

This has certainly been a lot to digest, but it was a delicious meal of brain food to dive into!

Resources cited in this post:

Reading Time: 5 minutes

Written: April 29, 2020

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On my most recent trip to India, one of my cousins asked what I would like (as a gift), but I’m not one to be picky about gifts just for visiting family! Of course, I brushed off her offer (politely, haha), but she insisted.

Knowing I’m the “researcher” of our clan of cousins, she gifted me with a book by a favorite author of some of my uncles and my Dad: The Body by Bill Bryson.

It was a hefty book to bring back from India, but I was curious to see what Bryson, a master of science communication, had to say on the broad topic of the human body.

In an effort not to end up writing a blasé book review (because that is not my intention…), my focus will be on specific points Bryson brings up that I found fascinating, intriguing, and even controversial given the all-too-fresh COVID-19 pandemic.

As you can tell from the length of the Table of Contents, it seems to me as if no sub-topic of the human body was left abandoned…

Within the first couple of pages, you can tell that Bryson has a way of describing the components of the human body with humorous curiosity.

He also threads in history throughout the book, noting the quirky, weird, and heroic actions of scientists back in the day, and how their fascinations led to the discoveries we know of today.

There’s also a mix of sociology, with one quote that really stood out:

It makes you think, doesn’t it? That skin pigmentation—the very thing that stirs up wars, targeted-violence, and micro-aggressions—arises from a sliver of skin approximatey 1 millimeter thick.

You could probably guess that my obsession with the “skin chapter” indicates my overall fancy of the book, and you wouldn’t be far off. I found some chapters more interesting than others—for example, a few chapters in, when I got to “The Chemistry Department”.

The section itself discusses the history and difficulties of treating hormone-based disorders, but what caught my attention was the complications with oxytocin, and how the difficulties of studies focused on it describe the trials and tribulations of biomedical research in general.

Oxytocin is famously known as a “motherly” hormone, in the sense that it is what drives the emotional connection between mother and child; it drives uterine contractions in childbirth and induces the production of breast milk. It doesn’t stop there though—Bryson notes that the hormone also plays a huge role in facial recognition and helping us to interpret moods in other people.

You’d think that in vivo animal studies would help us elucidate oxytocin’s mechanisms, but it has done the opposite. In a rat-based study, females given oxytocin were driven to increase production of nests and care for pups even if they were born to a different mother. On the other hand, oxytocin clinically administered to humans had no effect or rather, a negative effect, causing patients to experience more aggressive and less co-operative behaviors. The point is, the very insignificant size of a hormone belies the huge impact it has on our body.

What caught my attention as well was the the “Deep Breath” chapter. The fact that I landed into a discussion about sinuses and lungs in the middle of the COVID-19 pandemic seemed like more than a coincidence—this book was published in October 2019, and after I read about the nature of a sneeze, I was wondering why on earth the CDC didn’t recommend the usage of face masks by the general public much earlier at the onset of the pandemic…

Bryson highlighted the work of Dr. Lydia Bouroubia of MIT, a “sneeze expert” if you will. Sneeze droplets can travel up to approximately 26 feet and can drift in the air for 10 minutes before landing on surfaces. A sneeze itself was found to be comparable to a sheet of liquid film versus a collection of individual droplets flying out separately, but together. Temperature also plays a role in how sneeze droplets fuse together, an action more favorable in colder weather.

All of this would have been valuable information for the general public to be aware of pre-COVID. But perhaps these times have ignited a curiosity for people to further their understanding of infections and how they spread…I only hope.

If I’m mentioning covid, might as well highlight the “When Things Go Wrong” chapter. It’s uncanny how Bryson’s paragraphs on epidemics is so fitting for the times. Given that it takes months—years even—from the inception of a book to its release on bookstore shelves, you could almost say Bryson’s depth of (digestible) information on infectious diseases was a foreshadowing event. Like, Bill Gates Ted Talk circa 2015 level.

“A successful virus is one that doesn’t kill to well and can circulate widely,” Bryson writes, when he discusses the 1918 Spanish flu: an epidemic that thrived because of the contagion’s persistence and contractability. On the other hand, Ebola tends to be highly lethal but this characteristic lends it to be slow-spreading.

To me, the most striking characteristic about (most) infectious diseases are their origins—their zoonotic origins. Whether you consume animals or not, the data is there to interpret. The domestication of animals brought along with farming and agriculture also brought along leprosy, plague, tuberculosis, typhus, diphteheria, measles, influenzas, and coronaviruses…

I think nature is giving us big clues about something…

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Overall, the publication of Bryson’s book and when I read it could not have happened at a “better” time—a time of a newfound respect for things science. The discoveries that make science take patience, organization, and creative thinking that only certain individuals may find solace in, but its communication should not be restricted.

Bryson does an amazing job distilling the biology, throwing in creative descriptions, and chuckle-worthy anecdotes to make the human body a topic more approachable to the layperson…and it needs to be.

COVID-19 has proved/continues to prove that it is imperative for the general public to have a solid understanding of science. Like I said earlier, the simple observation that a sneeze is more of a liquid sheet versus individual droplets sprayed out sporadically in various directions paints a better picture for someone, who can then make a conscientious decision to wear a face mask and understand why they should.

Need a good read?

Want to come out of this pandemic feeling like an expert in biology?

Then I recommend this knowledge-packed piece of literature. 👌🏽

The Women’s Brain Book by Dr. Sarah McKay

Digestible Science – CD8+ T Cells and COVID-19

The Body by Bill Bryson