BioScope

A UC Davis Graduate Student Blog

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Internet Accountability

Written by: Devan Murphy

Edited by: Jennifer Baily

Due to the pandemic, most of us are spending more time in front of our screens. Honestly, I spend a lot more time on social media than I used to, and it has affected my mental health. No, it isn’t the dreaded FOMO (fear of missing out). It’s the posts from some of my friends and family that have shattered my perception of the people I thought I knew. As I scroll, I see an accumulation of conspiracy theories about COVID, unwillingness to help protect others by wearing a mask in public, and little empathy or consideration for the essential workers and medical professionals putting their life on the line while we sit at home. Although the internet is a valuable tool with a wealth of information and a method for connecting people, it can also be used for the complete opposite—disseminating falsehoods and driving a wedge between communities.

This weighs heavy on my mind and heart as people who helped raise me and shape who I am today share and legitimize misinformed views on the pandemic. But the information they insist on propagating results in behavior that goes against the very values I learned growing up. To see them posting harmful opinions and incorrect information feels like an attack on my profession. As a student in the Veterinary Student Training Program, I reside at an interface between the medical and basic science fields. To me, this situation is similar to clients who come into the clinic, ignore your professional opinion, and insist on telling you how to do your job because Dr. Google diagnosed their pet’s ailments for you. In the light of COVID, research scientists are now getting a taste of this frustration dealing with a population that is either ignorant or belligerently dismissive of facts (although climate change scientists have known this pain for a while now).

I do understand how the public could be confused. There is SO MUCH information out there, but this is what we deal with in science all the time. And as graduate students, I think we are exceptionally good at updating our point of view when we receive new data. I remember a conversation with a family member about grocery bags. He was annoyed about paper bags being brought back into fashion. It went something like this:

I don’t understand. We used to use paper bags, then they told us not to cut down trees, so we all switched to plastic. Now, everything is “Plastic is bad, plastic is ruining this environment.” So, which is it? We are supposed to go back to killing trees?

I tried to explain that as we get new information, we need to reimagine our behaviors. It is natural for scientists to understand that nothing is simple. There are always things we don’t know; we live on the frontier of the known and undiscovered. As we find new information and uncover confounding variables, we build them into our understanding or understand when to reject them. I wish it was easy as a superhero movie, where the bad guy is easily identifiable. But that’s not the real world. It is messy and problems are multifactorial, and clear straightforward solutions rarely exist. But here is the irony, in this situation, a common enemy does exist! Coronavirus. So, with a clear threat in sight, why are some people insistent on defying health experts instead unifying to defeat the pandemic?

Initially, who knew what to do? Wear a mask, don’t wear a mask? And unfortunately, with government leaders not always being the most reliable sources, downplaying the severity of the problem and being slow to take action, it can be very confusing for someone watching the news to know what actions to take. However, now it is clear this virus is very contagious, deadly, and masks help prevent transmission. Therefore, perpetuating misinformation and bashing public health guidelines is a safety concern.

So, as graduate students, a community versed in critical thinking and evaluating primary literature, is it part of our job to combat misinformation online? Is it our place? And what internal conflict does this pose to call out our family members or friends? Interestingly, I wanted a career in science because I thought it was the unbiased pursuit of facts, untainted by the subjectivity of the humanities. Why deal with people when numbers don’t lie. But numbers can lie. In the worst case, they are purposely manipulated(1), but even in the best of circumstances, statistics without context mean nothing. And without placing these numbers in the proper context, it is easy to misdirect the audience. As recent events have made perfectly clear, science is not devoid of these conflicts. Our science is funded by taxpayers to help the public, therefore, getting involved to make science interpretable and usable to the public is implied in that paycheck.

Leaders and officials seem to be catching up on the relevance of internet accountability. The United Nations started an initiative to provide reliable information about COVID(2) and some social media sites like Twitter began fact checking posts(3). But to do this, you need to critique the information. Scientists do this all the time with peer review, disclosing conflicts of interest, and discussing the limitations of their work. However, it takes time to go through and fight/debunk all of the misinformation. In contrast, it takes NO effort to make stuff up to support a false narrative. I’m lucky enough to still have my job, and I honestly don’t have the time to refute all the misinformation I come across. To some extent, it must be the responsibility of the individual to self-educate. Again, there is a wealth of information online.

While I strive to stress the importance of accountability online, I acknowledge that this may not be an entirely safe conversation as people feel attacked when you dispute their worldview. So much of science has been tied to politics, which becomes emotional quickly. Being rejected or cut off by loved ones may not be an option. But if possible, in the way that personally works best for you (1-on-1 conversations, public sharing of valid resources, etc.), I think we have some responsibility as a science community to stop the spread of misinformation. That doesn’t mean everyone will listen, but letting this information spread unchallenged, like the virus, is dangerous.

(For more information, about spotting misinformation and fighting it, check out Fleming’s article (4) )

 

  1.   Florida and Georgia facing scrutiny for their Covid-19 data reporting – CNN. https://www.cnn.com/2020/05/20/us/florida-georgia-covid-19-test-data/index.html.
  2.   Online training as a weapon to fight the new coronavirus. https://www.who.int/news-room/detail/07-02-2020-online-training-as-a-weapon-to-fight-the-new-coronavirus.
  3.   Twitter fact-checks tweets linking 5G and coronavirus – Business Insider. https://www.businessinsider.com/twitter-factchecks-tweets-5g-coronavirus-2020-6.
  4.   Fleming, N. Coronavirus misinformation, and how scientists can help to fight it. Nature 583, 155–156 (2020).

 

Far From Home

Written by: Ellen Osborn

Edited by: Ross Wohlgemuth

Many of us leave home in order to attend college. It is a modern-American rite of passage when we throw what physical items we care about into a suitcase and leave the place and people that, up until that point, were our whole world. And yet, the physical separation that is a defining part of the university experience is rapidly overshadowed by the emotional separation formed as we build social networks and expose ourselves to new perspectives. The learning and expanding that occurs at university can reinforce values learned at home, strengthening core convictions about how life works and what matters most. It can also deconstruct, maybe even shatter, parts of you. After a few years, the physical distance separating you from home can still be overcome by modern day travel, but the psychological distance that develops can feel increasingly unbridgeable. In my case, my childhood home is not too far from where I attend university, but the separation I feel from the community that raised me is devastating.

I was a difficult kid. I got into fights in school, did not make or keep friends easily and was aggressively tomboyish. I vividly remember laying on my bedroom floor as a nine-year-old, thinking that I hated everyone around me and did not understand why I was alive. My mom, the exceptional person that she is, decided to homeschool me during those rough years. We joined a small, Christian fundamentalist homeschool group, and through the years, I grew into a completely different person. The people in my new community shaped me; due to their efforts, I began caring for others, making friends and appreciating the value of my life. Because of this personal transformation, I feel a deep sense of love and gratitude toward my home community. I understand their actions were well-intentioned, and the lessons they explicitly and implicitly taught me came from a place of love and concern. In addition to the lessons of love and kindness, they taught me that homosexuality, abortion, evolution and even liberalism were evils in this world. They taught me that a woman’s ultimate purpose in life is to stay pure, marry and have many children. They taught me that California public universities would rob me of my faith and scientists could not be trusted. I believed most of what I was taught and arrived at community college with my guard firmly up. 

Despite the anti-science views entrenched in my home community, I was drawn to science. After only a few classes, science no longer seemed to be the amoral machine of secularization whose design was to deceive. Rather, I saw science to be a study of the complex beauty of the world around us. Continuing my education as a transfer student in a biology major, I learned more about nature’s detailed complexity and what I learned was not always compatible with my first worldview. LGBTQ+ people are not immoral; women are research powerhouses in academia; evolution is supported by evidence. 

Parts of my worldview needed to be reconstructed in order to accommodate my newly acquired relationships and knowledge. The longer I lived in my new community of friends, classmates and mentors, the more lessons from my upbringing were replaced by lessons from my adult life. This exchange did not occur because I was swept up in the groupthink of an institution; instead, I was developing love and empathy for the people who shared with me their values and beliefs and challenged the narrowness of my worldview. I still loved my home community, but our vantage points were no longer the same. In addition to the physical distance separating us, there was a growing psychological distance created by every lesson I no longer believed. 

The 2016 election revealed the immediate consequences of the psychological separation from my home. People I loved and respected were unreservedly saying things I once agreed with but now considered to be wrong. Vitriol and outright insults were leveled by both of my old and new communities. I could feel my conscience pushing me to be a bridge between the divide, but I felt like an imposter in both places. I had, in a way, abandoned my home community both physically and psychologically, and yet I still felt loyal to those people and understood their anger. Ultimately, my feelings of self-doubt and anxiety associated with sticking even a toe into the maelstrom of outrage relegated me to the position of a conflicted observer. Finishing college in a post-2016 world and becoming a graduate student in a STEM field, my observer status persisted. 

The events of this year have forced me to reevaluate my role in this divide. Rampant misinformation and prejudice are reinforced by closed social networks. Opponents, including scientists and peers I respect, degrade and publicly reprove these groups, the effect of which is to further feed the machine of mistrust and distaste. As an observer, it seems as if I am already conceding defeat: anything I say will be immediately drowned out by the outrage. 

But I do not want to be characterized by defeat. What if I can connect, listen and engage with just one person on the other side, and lessen the outrage they feel? What would happen if we gently correct misinformation when we see it and offer evidence that breaks the cycle of confirmation bias? Could we slowly build bridges that narrow the psychological separation between divided communities? I am just beginning to grasp the enormity of America’s culture war between science and fundamentalism, so these questions could be a result of my naiveté. When I doubt my ability to bridge the gap, I think of Barack Obama, who overcame the institutions framed against him to become the first Black president of the United States, and his quote: “Change will not come if we wait for some other person or some other time. We are the ones we’ve been waiting for. We are the change that we seek.” 

It is painful to parse out the consequences of psychological separations from the people we love, and even more so to take the next steps to try to bridge that separation. Fortunately, it is not just one person’s job to build that bridge; I’ve had many encouraging conversations with other graduate students that are reaching out to their home communities in small but meaningful ways. Even if that is all we can do now, it is a start. 

 

To be continued.

It’s time to get deep (TMS).

Written by Jen Baily 

Edited by Anna Feitzinger

Illustration by Sydney Wyatt

 

As I sit with earplugs in my ears, a tight velcro cap and a firmly secured helmet on my head, my right hand and right eye twitch of their own accord while the magnetic field creates a drumroll sensation two inches into my skull. It only lasts three seconds, but repeats over twenty minutes until my session is complete. This will continue every day for a month, then twice a week for two months. 

As someone with drug-resistant major depressive disorder (MDD), there are few options available to treat my symptoms, especially after being on the maximum doses of 5 different medications over the last few years. Electroconvulsive therapy (ECT), colloquially known as shock therapy, is often used as a last resort; however, it can cause severe memory loss and brain damage. Anecdotally, I’ve known friends that have undergone ECT who were never the same, which took it off the table for me. It wasn’t until meeting a psychiatrist to manage my medications that I learned about deep transcranial magnetic stimulation (dTMS), and how it is a non-invasive procedure for which I was a good candidate.

From the paragraphs above, as well as the name dTMS, you probably get the idea that dTMS is a deep, skull-penetrating magnetic pulse. How can this be used specifically to treat depression? The idea behind dTMS is to use this magnetic field to affect neurons, which act as conductors.

 In 1985, Anthony Barker and his associates produced the first transcranial magnetic stimulation (TMS) device. It was based on Faraday’s discovery in 1881, where a magnetic field was created by running electricity through a coil. By rapidly switching the magnetic field’s intensity or direction, you can depolarize neurons in a specific region of the brain. Though not fully fleshed out, it is thought that increasing the neural activity in the mood center of the brain, the dorsolateral prefrontal cortex (DLPFC), may be the mechanism by which dTMS alleviates symptoms of depression

The treatment targets the DLPFC on the right side of your head. The psychiatrist or technician finds the DLPFC  by applying magnetic pulses until your hands begin to twitch, indicating the magnetic fields have reached the motor cortex.   This allows the doctors to position the helmet containing the magnets over the DLPFC and to induce the firing of neurons in the area. dTMS is akin to Transcutaneous Electrical Nerve Stimulation (TENS) machine, except dTMS is specialized to stimulate the brain while TENS is inTENded (pun) to reduce pain. Nevertheless, the principle of manipulating the nervous system to the benefit of the patient remains the same. The neural activity  caused by the dTMS magnets increases expression of brain derived growth factor (BDGF), increased neural outgrowth and connectivity in rats (Paus, 2011), and showed a major elevation in mood of patients relative to a placebo treatment during clinical trials (Yates, 2016). BDGF accomplishes these tasks due to its role in development, maturation, and maintenance of neurons. 

By increasing the activity of neurons in the brain regions typically affected in patients with MDD, a burst of growth is thought to follow the acute/intense phase of treatment, when a patient is going in every day. During the second phase, where a patient is treated a few times a week, the activity is thought to be maintained while the brain adjusts. Relative to previous models of the TMS technology, deep TMS has an excitingly high “remission rate of 32.6 in active deep TMS (vs 14.6 sham treatment)” (Levkovitz, 2015). Remission of MDD is typically thought to be a significant decrease in depressive symptoms for longer than 4-6 months (Frank, 1991). While this may seem like a low number, for someone suffering from depression, any reduction in symptoms can be helpful, and full remission of symptoms can allow someone to function normally. For the third of patients who’ve never felt relief, this is life-changing.

After extensive studies on rats and clinical trials on humans, the FDA approved dTMS use for patients who had failed 2 or more medications during their current episode of depression. Because dTMS is not a medication, simply a locally applied magnetic field, it is without the usual side effects such as “weight gain, sexual dysfunction, nausea, tremors, dry mouth, diarrhea, headaches, constipation, sweating, sleepiness or anxiety” that are associated with antidepressant use (History of dTMS). What’s wonderful, in my opinion, is that the patient can drive to and from their appointment. There are minimal side effects that usually dissolve shortly after a treatment session. Apart from the super magnets being quite noisy, the strangeness of the feeling itself, and occasionally scalp tenderness, it really is an amazing option for patients with drug-resistant MDD.

If dTMS is such a wonder “cure” for depression and anxiety related disorders, 1) why haven’t more people heard of it and 2) why don’t more people utilize this technology? To address question one, I’ll quote my lovely psychiatrist, “stigma.” There is a certain stigma associated with a daily treatment regime, especially one that requires transportation to a clinic. Though effective, it is a new technology and can often be lumped together with ECT in the public eye, which can be a traumatic experience for patients. To address question two, dTMS is very expensive. UC student health insurance is quite good for mental health services, but even then, I had to fail out of 5 medications and rate at a specific level of depressive symptoms prior to any coverage for almost a year. Failing out of medications involved either severe side effects or lack of effect for 16 weeks of treatment. If the insurance company doesn’t think you’ve gone hard enough for long enough, they can request that you take higher doses of medication prior to approval. All this is associated with the side effects mentioned previously, and during this time the patient is suffering. Additionally, a patient may be suffering to the point of suicidal ideation, but is functional enough to score below the required threshold on a PHQ-9 form. If a patient battling with depression must be their own advocate while on heavy medications and experiencing symptoms, getting to a place where dTMS is possible can be difficult. However, things are starting to change for the better.

As dTMS becomes a more mainstream treatment option, more and more patients are seeking it out to ameliorate their symptoms. Along with the patients themselves feeling better, those in their lives are able to notice improvements. My own partner told me that I was able to carry a conversation for significantly longer after a month of treatment relative to my depressive episode. As more and more people notice the impact that this treatment has on their loved ones, word will spread. Additionally, within the past 10 years, mental health stigma has significantly decreased. Now, I can openly talk about my own experience with minimal impact to my career prospects, and am still viewed as a functional and contributing member to my community.

In learning about dTMS for my own sake, I was amazed by the scientific literature behind it. The technology brings together physics and physicians, neuroscientists and patients. Through their creative and thorough research, hope has been brought to many suffering with MDD, myself included. If you or someone you know has struggled with a severe depressive episode, perhaps now is a good time to discuss dTMS with your physician  or other new technologies as treatment options. And always remember, reach out if you need help. You’ll be surprised by how many people and how many treatments out there can help.

 

On campus services – UCD specific

https://leadership.ucdavis.edu/strategic-plan/task-forces/mental-health

  • Individual counseling
  • Couples counseling
  • Group therapy
  • Skills groups
  • Case management
  • Career counseling
  • Outreach to the campus community

They only work if you use them.

 

Partial Hospitalization and Intensive Outpatient Programs

Group therapy at a hospital location, often using cognitive behavioral therapy, with access to on-call psychiatrist and nurse.

 

National Suicide Prevention Lifeline

We can all help prevent suicide. The Lifeline provides 24/7, free and confidential support for people in distress, prevention and crisis resources for you or your loved ones, and best practices for professionals.

Online Chat – Lifeline

1-800-273-8255

 

“Warm Line” – Talk to trained listeners before a crisis: Visit http://www.warmline.org/ to find the number for your area.

Talk to trained listeners over text: https://www.crisistextline.org/

 

References

http://www.brainefit.net/history-of-tms.html

Yates E, Balu G. Deep Transcranial Magnetic Stimulation: A Promising Drug-Free Treatment Modality in the Treatment of Chronic Low Back Pain. Del Med J. 2016;88(3):90‐92.

Johnson, Mark. “Transcutaneous Electrical Nerve Stimulation: Mechanisms, Clinical Application and Evidence.” Reviews in pain vol. 1,1 (2007): 7-11. doi:10.1177/204946370700100103

Levkovitz, Y., Isserles, M., Padberg, F., Lisanby, S. H., Bystritsky, A., Xia, G., … Zangen, A. (2015). Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial. World psychiatry : official journal of the World Psychiatric Association (WPA), 14(1), 64–73. doi:10.1002/wps.20199

Tomáš Paus  Manuel A. Castro‐Alamancos  Michael Petrides (2011). Cortico‐cortical connectivity of the human mid‐dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation. European Journal of Neuroscience. 14(8), 1405-1411. https://doi.org/10.1046/j.0953-816x.2001.01757.x

Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW, Rush AJ, Weissman MM. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991 Sep; 48(9):851-5.

In memory of Syndey Brenner: his part of the discovery of messenger RNA

Written by: Hongyan Hao

Edited by: Ellen Osborn

All biology undergraduates learn the central dogma: DNA makes RNA and RNA makes protein. However, not long ago, this dogma was intensely debated because it was unclear if DNA or protein contained the genetic material of the cell. The famous double helix model opened the door to molecular biology in 1953. But it took an additional eight years to discover the messenger RNA. Sydney Brenner, who shared the 2002 Nobel Prize in Physiology or Medicine, was a key traveler in this long journey.  

Portrait photograph of Sydney Brenner, c. 1960s, 
Copyright: MRC Laboratory of Molecular Biology

 

 

 

 

 

 

 

 

 

 

As described in his autobiography, My life in Science, Brenner thought about how genetic information guides protein synthesis even before he saw the double helix model in April 1953 at Cambridge. Inspired by the similar step size of nucleic acid (3.5 angstrom units) and amino acids (3.3 angstrom units) pointed out in William Astbury’s 1947 paper, Brenner developed his “pet theory” that amino acids join together at the same time nucleic acid strands are synthesized. At the time, people knew that DNA sequences defined proteins, but it was not clear whether there was an intermediate molecule between DNA and protein. With the discovery that protein synthesis occurs at ribosomes, it was largely assumed that the intermediate was the ribosomal RNA (rRNA). However, some people were skeptical about this. One reason for this skepticism was that in bacteria, the ratio of the amount of G+C to A+T in DNA varied a lot between bacteria species, while in rRNA the variation was trivial.

Another concern was what Brenner called the “paradox of the prodigious rate of protein synthesis.” While working with bacteriophages at Cambridge, Brenner and Francis Crick observed that after phage infection, 70% of protein made in the infected bacteria was the phage head protein instead of the bacteria protein. If rRNA is the intermediate for protein synthesis, a significant increase of new rRNA should be observed. However, there was no detectable rRNA synthesis. In 1956, Elliot Volkin and Lazarus Astrachan discovered that a small amount of short-lived RNA resembles the phage DNA in base composition rather than the bacterial DNA after phage infection, however, they were kind of focused on the idea that these new RNA could be the precursor of phage DNA. 

Four years later, the secret of the mysterious Volkin-Astrachan RNA was uncovered in Brenner’s living room. It was during an informal meeting of a small group of scientists, including Crick and François Jacob from Institut Pasteur in France. Jacob described the new findings from the famous Pardee, Jacob and Monod (PaJaMo) mating experiment. Normally, bacteria synthesize galactosidase in a medium containing lactose. However, the lac- mutant cannot digest lactose until the gene that encodes the galactosidase is transferred into the cell. Galactosidase synthesis is extremely rapid, happening within minutes. Interestingly, when they let the bacteria produce galactosidase for some minutes and then destroyed the transferred DNA, galactosidase synthesis stopped immediately. These results ruled out the possibility of any stable intermediate like rRNA because if the intermediate were stable, galactosidase synthesis should have continued for a while after the gene was removed. Upon hearing Jacob’s description, suddenly, Brenner got excited and shouted to Crick, “Volkin-Astrachan; information intermediate; it’s short-lived; a short-lived intermediate! It must be! Look at the way it turns over in phage!”

The next step was to plan experiments testing whether the short-lived RNA was the intermediate messenger that guides protein synthesis. If Brenner’s hypothesis was correct, then the new RNA intermediate synthesized after phage infection should be associated with the old bacterial ribosomes.To do this, they needed a way to distinguish between the ‘new’ and ‘old’ ribosomes. Lucky for them, Matthew Meselson and Frank Stahl at California Institute of Technology (Caltech) developed the density gradient centrifugation experiment and successfully separated the isotope N15-labeled DNA from the N14 DNA in a caesium chloride solution. The RNA intermediate experiment could use this approach to label bacterial ribosomes with isotopes before phage infection and resuspended in the medium without isotopes right after infection, which would make the old ribosomes heavier than the new ribosomes and therefore distinguishable by density gradient centrifugation. 

Jacob and Brenner went to Matt Meselson’s lab in California the following summer to test their new hypothesis. The experiment that followed was, as described by Brenner himself, a “hilarious story”. The experiment itself was complex, isotopes were expensive, samples needed to be spun in the centrifuges for nearly 20 hours or more, and the centrifuges were unreliable. And they only had three weeks! The first problem Jacob and Brenner encountered was that the ribosomes were not stable and dissociated during sedimentation in the centrifuge. They tried to troubleshoot, but to no avail. They even thought of purifying ribosomes from Dead Sea bacteria because they already live in a high salt environment and might be more tolerant of the high concentration of caesium chloride. Unfortunately, their phage couldn’t infect the Dead Sea bacteria. 

Frustrated and tired, they went to a nearby beach to, in Brenner’s own words, “rest their weary souls”. Jacob recalled this time in his autobiography: “There we were, collapsed on the sand, stranded in the sunlight like beached whales. My head felt empty. Growing, knitting his heavy eyebrows, with a nasty look, Sydney gazed at the horizon without saying a word.” Lying on the beach, it occurred to Brenner that magnesium stabilizes the ribosomes and the high caesium could displace the magnesium, making the ribosomes unstable! They ran back to the lab and set up their last-chance experiment of three samples with higher magnesium concentrations. During the chaos, Jacob dropped the radioactive phosphate in the water bath and the centrifuge broke down in the middle of the experiment! Luckily, they were able to borrow a centrifuge from a neighboring lab. Nervously, Brenner carried the rotor with the tubes to the cold room. He walked there because the elevator would shake the tubes, destroying the gradient he had worked so hard to create. In the end, they managed to finish the experiment and showed that the new radioactive RNA peaked at the same position with the old ribosomes! Later, these results were published in Nature in 1961, along with the discovery from James Watson’s lab that a fraction of rapidly labeled RNA of different sizes were associated with the ribosome active site (where protein synthesis happens). That same month, the term “messenger RNA” and it’s possible role in gene regulation was discussed in Jacob and Monod’s review article in Journal of Molecular Biology.

Even today, the exploration of messenger RNA never ends. I’m fascinated with how the friendship between scientists, critical thinking, effective communication, and collaboration all contributed to the discovery of messenger RNA. When we hear stories about scientific discoveries, it often sounds like a genius just appeared and came up with an idea that changed the world. But Sydney Brenner’s story shows that it’s not that simple. Scientists can make wrong hypotheses, create naive models and misinterpret results. Sometimes, experiments won’t work; sometimes people tell you not to try an experiment because it is unlikely to work; sometimes you get weird results; sometimes people question and laugh at your hypothesis. But sometimes you make fascinating discoveries. Sydney Brenner passed away in April 2019 at the age of 92. Brenner’s obsession with science, creative thinking, open mindedness, and persistent pursuit of answers will continue to inspire scientists like myself.

 

Sources:

  1. Brenner, Sydney. My Life in Science. London, 2001.
  2. Hernandez, Victoria, “The Meselson-Stahl Experiment (1957–1958), by Matthew Meselson and Franklin Stahl”. Embryo Project Encyclopedia (2017-04-18). ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/11481
  3. Meselson, Matthew, and Franklin W. Stahl. “The replication of DNA in Escherichia coli.” Proceedings of the national academy of sciences 44.7 (1958): 671-682.
  4. Brenner, Sydney, François Jacob, and Matthew Meselson. “An unstable intermediate carrying information from genes to ribosomes for protein synthesis.” Nature 190.4776 (1961): 576-581.
  5. Gros, François, et al. “Unstable ribonucleic acid revealed by pulse labelling of Escherichia coli.” Nature 190.4776 (1961): 581-585.
  6. Morange, Michel. “What history tells us XLV. The ‘instability’ of messenger RNA.” Journal of biosciences 43.2 (2018): 229-233.
  7. Cobb, Matthew. “Who discovered messenger RNA?.” Current Biology 25.13 (2015): R526-R532.

How to Make Your Zoom Presentation Pop

Written by: Tess Gibson

Edited by: Sharon Lee

 

Viewers join one by one, and presentation time is about to begin. But how do you grab the audience’s attention when they’re miles away? Here are some tips to make your Zoom presentation stick out from the crowd. 

 

Use eye contact

The nature of online presentations allows you to make every audience member feel you are speaking directly to them. However, this only works if you’re looking directly into the camera.  Though it may not come naturally, you should look into the little green light as much as possible so your audience can sense that you are present despite your distance. 

 

Emphasize your verbs

No one wants to listen to a monotone lecture, and there’s even less incentive over Zoom, when you can turn off your video and snooze away. When you give a presentation online, a monotone lecture may even make it appear that you’re reading off of a script. A sure way to add interest is putting action into your verbs. Try writing out your hook and highlighting your verbs. For example, one should ask “how do we stop cancer?” instead of mumbling “how do we stop cancer?”. Use this to practice bringing life into your presentation and then transition to practice without your script. Adding a little extra excitement and inflection to your verbs grabs the attention of the audience and keeps them engaged with wherever you’re taking them next. 

 

Use animations

Most people know to try to limit the amount of words on a slide, but what do you replace them with? Animations! Using animations is a great way to “show” your audience rather than “tell.” You want the audience focused on your visuals, not reading a complete sentence off of your slide. Start with the basics by animating circles or arrows to appear on command as a way to highlight portions of your images. Then, take it up a notch by animating images to appear one after another using timing controls to achieve a sequentially animated talk that seems almost more like a movie than a presentation. If building multiple animations into one slide is daunting, you can also use multiple slides to add or remove images with the same effect.

 

Keep it aesthetically pleasing

Nothing is more off-putting than a glaring typo or an unintentional shift in font halfway through a presentation. On Zoom, these tiny errors have an even greater impact because a majority of the screen is your slide. Proof-reading your presentation is a simple but key step in the preparation process. Some common issues to look for are…

  • Typos
  • Font size, type, or color shift
  • Lack of continuity (e.g. using complete sentences in some cases and not others)
  • Poor quality images
  • Mislabeled graphs and tables

 

If you include it, talk about it

It’s great to have figures, but if you don’t explain them, no one in the audience will know what they mean. Be sure to explain your axes, what the figure tells you, and how it relates to your main point. If the results are not conclusive, discuss that too. Try using the laser pointer feature in place of your mouse to explain specific parts of your figures as you talk about them. 

 

Squeeze your butt

Lastly, squeeze your butt! That’s right, go ahead and try it! This is a silly but useful trick to start off your presentation right. Plant your feet, straighten your back, and tighten your behind. Don’t worry, you don’t have to maintain this posture for your entire presentation. Feel free to relax and move your arms. This is just to start you off with a feeling of confidence and strength. 

 

With these tips in mind, your audience will need a magnifying glass because they’ll want to zoom in on your presentation!

Looking at case-number data for COVID-19

Written by: Keith Fraga

Edited by: Sydney Wyatt

The California shelter-in-place order due to COVID-19 has been in effect for over a month, with an uncertain end-date. Understanding how the disease is spreading by making predictions based on current data can help health officials in their decision on when to lift the order. There are a number of ways one can analyze the data on COVID-19 cases to model where the epidemic is heading.

 

Often, statistics on COVID-19 growth rate are given in terms of cumulative cases from the start of the epidemic. As an example using data from the Johns Hopkins COVID-19 resource site, the growth rate in the number of cases in the U.S. quickly surpassed Spain, which has the second highest growth rate, and it is still increasing. How this growth rate changes and ultimately decreases will be a major determining factor for the ending of shelter-in-place orders. Yet, it is difficult to model or uncover the trends in COVID-19 progression through a timeline of total infections, like in Figure 1, due to the exponential nature of the growth of total cases.

 

Figure 1: Total number of COVID-19 cases in U.S. (green) and Spain (red) based on data from Johns Hopkins.

 

In epidemiology, the spread of a disease undergoes an early period of exponential growth. Once the disease progresses to a point where no new infections can occur, the growth rate slows and the cumulative number of cases plateaus. This is called logistic growth, and an example of logistic growth is shown from the 2014-2016 Ebola outbreak data below. Looking at the steepest part in the curve in Figure 2, could we have known that the Ebola outbreak would plateau when it did?

 

Figure 2: Timeline for the cumulative growth of cases in the 2014-2016 Ebola outbreak. 

 

When there is only data from the middle of the logistic growth curve, it is challenging to predict when the curve will plateau. It is possible to make estimates of when an outbreak could plateau, but this requires looking at the data in a different way, described more below. The ability to predict and model this time to plateau, thereby estimating when the epidemic might be under control, will be a major factor in deciding when normal operations can resume.

 

‘The virus makes the timeline’ 

 

Dr. Anthony Fauci, the NIH infectious disease expert at the center of the U.S. response to COVID-19, gave some insight into interpretation of the outbreak. In a CNN interview on March 25th, Dr. Fauci explained that it is very difficult to know when we can return to normalcy. Further, our attempt to put a deadline on the virus is folly: “You don’t make the timeline, the virus makes the timeline.” How can we understand the virus’ timeline? This question exposes that time may not be the appropriate independent variable to track the epidemic’s progress. 

 

The growth of the virus depends on many factors, but fundamentally it depends on the number of currently infected patients that can transmit the virus. Mathematically, this is captured by modelling the infection growth rate as proportional to the number of currently infected. As more infected cases occur, the faster the outbreak spreads. Time – in days, weeks, or months – since the outbreak is an indirect way to track the virus’s progression. As more time elapses there are more transmission events, but how the outbreak grows is controlled by the number of infected patients. 

 

This argument indicates that time is not the best variable to be on the x-axis when looking at the outbreak’s timeline. Instead, we should look at the number of total infections versus the number of newly infected. As the number of new infections drop, the exponential nature of an epidemic begins to subside. On a (total infections) vs (new infections) plot, we can more readily see when the virus is slowing down.

 

Fortunately, people have already performed this analysis and made it freely available online. Figure 3 shows the growth of COVID-19 for the U.S, Spain, Italy, and China on a logarithmic scale. On a logarithmic scale, the tick-marks on the axes reflect a common multiplier, whereas on a linear scale the tick-marks reflect a common addition between numbers. Therefore on a logarithmic scale, the number of tick-marks between 1,000 and 10,000 is the same as the separation between 10,000 to 100,000 because both are separated by a multiplier of 10. Specifically, Figure 3 displays the logarithms of the absolute number of total and newly infected COVID-19 cases. China is experiencing a massive drop in new cases, and thus has reopened many parts of their country. Germany is experiencing perhaps a reliable downward trend in new infections. The U.S. has plateaued on the number of new infections, but this indicates that the outbreak is still growing, just not exponentially. This YouTube video describes how and why this analysis website was made, and is largely the motivation of this article.

 

 

Figure 3: Total confirmed cases vs new cases for US, Spain, Italy, and China (Source: https://aatishb.com/covidtrends/). 

 

Taking a deeper dive into the data, we can look at the cumulative cases over time for Germany and compare it to the plot in Figure 3. Figure 4 below illustrates how the drop in new cases (left plot) is a more discernible sign that the epidemic is slowing than the cumulative progression of the virus (right plot). 

Figure 4: Side-by-side view of two different ways to look at the COVID-19 epidemic in Germany. Source of plot on the right is: https://www.worldometers.info/coronavirus/country/germany/

 

We are in this together

 

By selecting all countries on the COVID trends website, COVID-19 progression exhibits very similar dynamics across the globe. This clearly shows this is a pandemic that severely impacts all countries. Countries and regions that are not yet overwhelmed can prepare based on experiences from the hotspot regions  

 

By looking at the progression of the epidemic in different ways, we can start learning more about how the epidemic grows and estimate when the number of cases starts to decrease. It is encouraging when watching, for example, Governor Cuomo of New York analyze the daily increases in deaths and new cases. While this analysis is not exactly the view we use in Figure 3 and on the Covid Trends website, examining daily increases in deaths and cases are useful barometers for the outbreak’s timeline. When those daily increases subside is when the exponential nature of the outbreak begins to plateau. Modeling and visualizing the pandemic will hopefully improve our preparedness for any future waves.  

 

Sources

 

  1. California, S. (2020). Stay home except for essential needs. Retrieved 28 April 2020, from https://covid19.ca.gov/stay-home-except-for-essential-needs/
  2. Cumulative Cases. (2020). Retrieved 28 April 2020, from https://coronavirus.jhu.edu/data/cumulative-cases
  3. Ma, J. (2020). Estimating epidemic exponential growth rate and basic reproduction number. Infectious Disease Modelling, 5, 129-141. doi: 10.1016/j.idm.2019.12.009
  4. Paul LeBlanc, C. (2020). Fauci: ‘You don’t make the timeline, the virus makes the timeline’ on relaxing public health measures. Retrieved 28 April 2020, from https://www.cnn.com/2020/03/25/politics/anthony-fauci-coronavirus-timeline-cnntv/index.html
  5. Covid Trends. (2020). Retrieved 28 April 2020, from https://aatishb.com/covidtrends/
  6. (2020). Retrieved 28 April 2020, from https://www.youtube.com/watch?v=54XLXg4fYsc
  7. Germany Coronavirus: 158,758 Cases and 6,126 Deaths – Worldometer. (2020). Retrieved 28 April 2020, from https://www.worldometers.info/coronavirus/country/germany/
  8. Sheridan, J. (2020). FILE: Slides from Cuomo’s 4/7 coronavirus briefing presentation. Retrieved 29 April 2020, from https://www.news10.com/news/ny-news/file-slides-from-cuomos-4-7-coronavirus-briefing-presentation/
  9. Caroline Kelly and Jen Christensen, C. (2020). CDC chief says there could be second, possibly worse coronavirus outbreak this winter. Retrieved 29 April 2020, from https://www.cnn.com/2020/04/21/politics/second-coronavirus-cdc-director-robert-redfield/index.html

 

Test Anxiety: COVID-19 Edition

Written by: Sydney Wyatt

Edited by: Jennifer Baily and Will Louie

 

If you’re like me, you’ve probably been panic-refreshing the Yolo County website for

Depiction of a swab collecting a sample from the back of the nasal cavity.

the newest case numbers as the COVID-19 pandemic continues. Case numbers continue to rise as testing capacity slowly increases, but social distancing appears to be flattening the curve in California. Disturbingly, there is still a huge backlog of samples to be tested and, currently, a high false negative rate. 

 

A nasal or throat swab is performed to get testable samples; according to one patient it “feels like they are swabbing your brain.” This sample is then shipped off to a laboratory to run a test to detect SARS-CoV-2 RNA. This involves RNA extraction, cDNA library prep, and finally RT-PCR to produce a band on an agarose gel that indicates a positive result. There is another method, approved by the FDA on March 13, that performs all these steps within a single automated instrument, but there is still doubt about whether it is better at extracting RNA without damage.

 

The FDA recently approved the use of Cellex’s antibody test, however antibody tests are not the best tool to diagnose illness. Antibodies develop to recognize and fight an invader, in this case the novel coronavirus; thus antibodies can only be detected during the late stages of symptomatic infection or after symptoms subside. It could help determine how many people actually had COVID-19, regardless if they tested negative or didn’t meet the testing requirements, however there is still debate whether antibody testing really works and demonstrates immunity. Antibody testing in California started on April 10. As of April 18, reports suggest that significantly more people have tested positive for antibodies than expected based on the laboratory test numbers.

 

While the initial World Health Organization (WHO) test implemented in January worked well for many countries, the Centers for Disease Control and Prevention (CDC) created its own test based on detecting different SARS-CoV-2 genes. While this test was shipped out starting February 6 after the CDC announced the first case on January 21, person-to-person spread was already occurring according to a CDC announcement on January 30 . The test was released under the Food and Drug Administration’s (FDA) emergency use authorization, meaning it was not vetted by the FDA prior to release. However,  problems with the negative control were reported as early as February 12. Labs found that the primers for the negative control were binding to each other to produce a false positive. The initial test batches with the faulty primers were recalled from general use, resulting in a bottleneck at the CDC lab in Atlanta, Georgia. The CDC approved modification of the test on February 26 on a lab-by-lab basis, although the test remains imperfect and there is a significant backlog due to the delay. This delay in testing between evidence of community spread on January 30th and the authorization of test adjustment on February 26th put the US almost a month behind on keeping the virus in check.  

 

While some county websites report the number of negative laboratory tests — like Santa Clara County in the Bay Area — there is currently a high false negative rate. Some reports indicate a 30% chance of a false negative, meaning 30% of those “negative” patients may actually have COVID-19. In some hotspots, this could significantly increase the number of positive cases. This inaccuracy can be caused by errors acquiring samples or during the testing process. The sample may not have enough genetic material. RNA is unstable and degrades easily, and the test process is difficult to troubleshoot due to complex steps. The antibody test may also give false negatives because not every patient will develop an antibody response as in the case of immunocompromised patients. RT-PCRs are notoriously finicky, yet they’re still the most sensitive testing method compared to antibody testing or culturing samples. 

 

As of April 2, there were a reported 60,000 pending tests in California alone; Quest Diagnostics — one of the largest private testing facilities in the country — reported a backlog of 80,000 tests on April 13. Again, these are RT-PCR tests that must be performed at private labs like Quest Diagnostics or university labs because the equipment is not widely available at the point of care. The testing bottleneck is further dependent on machine time and reagent availability. Accelerated results require the development of a sensitive sample-to-answer test that can be run at the point of care, similar to getting a flu test at the doctor’s office. 

 

A new point-of-care test from Abbott claims to detect infection in just 5 minutes using a specific proprietary machine already used in doctor’s offices across the country. It is important to note this test is also authorized by the FDA under emergency use authorization and will cease to be used when the authorization is revoked. Because it has not been officially vetted by the FDA, there are still doubts about its sensitivity.

While the backlog has been somewhat alleviated with 150,000 tests run per day last week, let’s keep it that way by staying home and physically distancing ourselves. Check out our articles about coronaviruses and maintaining your mental health while sheltering in place.

Diversity in STEM Conference: An Interview and Reflection

Written by: Aiyana Emigh

Edited by: Keith Fraga

 

Note: Interwoven into this article are parts of an interview held on Feb 12th with Alexus Roberts, third-year PhD candidate in Population Biology, who was one of the lead organizers for the Diversity in STEM Conference.

 

In the midst of university controversy over the valuation of faculty diversity statements in their application process, the students of UC Davis held their newly-expanded, annual Diversity in STEM Conference (DISC) on January 25th with the purpose of “[honoring] the progress that has been made towards diversity and inclusion on campus, in the industry, and beyond.” 

 

Me: How well did the events of the day meet your mission? Did you achieve everything you wanted to achieve?

Alexus: I think based on our mission and our purpose statements we were talking about bringing together marginalized students to create community… and [talk] about the barriers to marginalized students and how you overcome them. I think the panel alone addressed that. And then, honoring the progress that has been made on campus… those are really broad goals. We definitely addressed them but I think we have to collect feedback from people [over the next] couple years and … see if that [led] to internships or job opportunities. I think as a committee one of our goals is to create a pipeline for marginalized students to graduate from higher education on their own terms… That [will take] time.

 

Held in the ARC Ballrooms and filled with more food than everyone could eat, the day began with breakfast and time to mingle before sitting down for the first speaker. After splitting a cinnamon roll with the keynote speaker, Dr. Renetta Tull, because we both had a craving we didn’t want to indulge, I sat down to listen to a very inspiring morning of speeches and panel discussions. 

 

Dr. Tull’s keynote address “Joy in the Journey” outlined the meandering path she took to her current position as Vice Chancellor of Diversity, Equity and Inclusion. The title was inspired by a quote from Representative Ayanna Pressley of Massachusetts, “It’s alright to stand in joy…joy is a necessary act of resistance.” It was very clear from her talk that Dr. Tull intimately understands the mental health concerns of graduate students and personally experienced the bias and discrimination women and minorities face, especially within the STEM community, and wants to be an ally to current students who may be struggling. 

 

Her story highlighted that success may not always look like we imagined it to and we may need to rethink our trajectory, but if we focus on the problems that are important to us we can find our way. One part Dr. Tull shared that stuck in my mind was a section of a poem she wrote on her flight home from a speaking engagement on diversity in Latin America: 

I am out of the box, 

the voice you didn’t know you needed to hear, 

together we are better, 

join me in the struggle to lift others up.

This consistent message throughout her story was the need for resilience, mentorship, and community. “[Reshaping] environments [people exist in] can mean something. It can inspire.” We need to choose to surround ourselves with people who are going to build us up. 

 

Me: What did you enjoy most about the day?

Alexus: There was a certain point during the luncheon where I had to go up [on stage] and tell everyone … ‘here is what’s happening.’ And just seeing everyone out there talking, smiling and laughing, seeing them lining up to talk to the panelists–it was really cool. [The DISC Organizers] are really making a difference and making a space for community … [and] connections. 

 

This message of community was echoed throughout the remaining morning sessions. Two panels – “Transitioning from College to the Workplace” and “Navigating the Workplace in STEM” – consisted of four speakers* each plus the lead panelist and moderator, Dr. Devin Horton. I could fill up several pages with the stories, advice, clarifications, solidarity and support the speakers packed into this hour, but to sum it up through quotes by the panelists:

 

  1. “Don’t measure by how much help someone appears to need.” –Lakshmi Sharma
  2. “The system is not fair and you have to find ways to change it, but don’t let it compromise your mental health.” –Colleen Bronner
  3. “There is so much [we] don’t know and don’t realize. Mentors can help you figure out how prepared you are.” –Gwladys Keubon
  4. On dealing with imposter syndrome, adopt the attitude: “I don’t know it yet, but I will.” –Amanda Dang
  5. “Resources may have been there but not the knowledge of them or the thought I deserved them. Have the confidence to go after them. Move the resources closer to you.” –Barbara Blanco
  6. “My culture tells you to be humble and that if you put your head down and work someone will notice you. This doesn’t work. [We need to] encourage people who are doing well and give them the opportunity to be leaders. Doors open up from achievements but also from advertising them.” –Carlos Gonzalez
  7. “Always be willing to learn and grow no matter what position you are in.” –Linda Finley
  8. “The reimbursement system is b***s***.” –Crystal Rogers 

 

An important distinction made during this time that I don’t think is discussed enough is on the difference between mentors and sponsors. A mentor helps you through advice and support. A sponsor advocates for you, even when you aren’t in the room. During the Q&A, one student attendee spoke about his struggle with finding a sponsor. The response: Sponsorship requires trust; Invest time in them, in who they are and their personality. The truth is that these sponsor-sponsee relationships are investments and, when networking, the number one piece of advice someone can give you is to find what you can do for your sponsor. It’s not just about what they can do for you. Demonstrating what you can do for the sponsor and your developing relationship with them will encourage the sponsor to advocate for you when you are not in the room. 

 

Me: What challenges did you face?

Alexus: Everyone [who was planning this event] is a student. So making sure that we actually made time for all of this was difficult. I definitely know there was a good two weeks when I got back from winter break where I didn’t focus on anything else besides this conference. We had already been planning since June, but [this] was the time when everyone needed updates … Additionally, [the organizers] are strong visionaries and leaders … and when you have [many of these people] in a room together, there is a lot of back and forth about how we [wanted] things to be––making sure that everyone was happy with how this looked can cause tension sometimes. The last thing was student turnout. We had 100 students come which was incredible. And all the students that were there really gave some high praise and admiration for the conference overall. But, to put in all that work and have 100 of the 200 that RSVPd not show up was [frustrating]. I think people are busy but if you are involved in planning an event then, you know, that handful of people not showing up is difficult. 

 

Another important discussion graduate students need to have is on the balance between hard work and mental health. So many students come in and acquiesce to professors’ expectations or demands, or they don’t feel like they have the right to pursue their interests outside of their lab work. Complicated by a power imbalance and centuries of tradition, the relationship between PI and student can be wonderfully supportive and productive but it can also be very contentious

 

Also asked in the Q&A was how to bridge the gap between working hard and maintaining mental health. The response: Taking care of yourself improves your work. Set boundaries and priorities, and commit to your hobbies. Most importantly: Learn to say no. “No” is a complete sentence. This advice should be given to every graduate student walking on to campus and will continue to be relevant as we move on in our career. Women and minorities are often asked to contribute more of their time on average to serve on committees and be present because of these efforts to diversify. This means the people often struggling hardest to stay afloat are the same people with more pressure and responsibilities.

 

Me: One point brought up in the panels was how people may have access to resources but didn’t know they were there. What are your thoughts on trying to make all the resources known to people, whether on campus or in general?

Alexus: I think it’s difficult because we have all these different mediums to connect with students and make sure that what you have to offer is out there. The people providing the resources… have to do their part to advertise it and make it accessible to people… I know it can be very overwhelming to try to look for all those things and when you are struggling it is very hard to be like ‘I can go and I can do this thing.’ 

 

After the lunch break and conversations with the interesting women at my table, we split up for an afternoon of workshops. There were three options for each of the two workshop sessions divided into two tracks: graduate and professional. For my first session, I attended the “Conflict Management”  professional track option led by two student interns from the Center for Leadership and Learning which began with an exercise where we individually chose four words that we associated with the word “power.” I chose (1). Money, (2) Politics, (3) Corruption, and (4) Confidence. We then paired up and were tasked with narrowing down our combined eight words back down to four by advocating for more of our words to be included in the final set than our partner’s. Then, our pairs combined with another group and repeated the process but this time arguing for more of the other group’s words to be included in the final set. This activity was accompanied by debrief questions about what it revealed about your approach to conflict and was followed up by a quick conflict management style assessment similar to the one linked here that assigned an animal (I’m an owl apparently) to different approaches to conflict. The last session before the career fair, ”Stories from Professionals,” consisted of guest speakers talking about their career paths and experiences. Their advice reiterated many points made during the morning panels but could be boiled down to: reach out and make as many connections as possible. Not only do opportunities open when you meet new people but it exposes you to differing viewpoints that improve collaboration and broaden your perspective.

 

Me: What did you find disappointing about the conference?

Alexus: From a little feedback from people, making sure that this is useful for graduate students. All the undergrads really seemed to enjoy it, but I want to make sure we are serving the general  UC Davis student body. So, making sure that the people we are inviting to lead our workshops are aware that we have grads and undergrads. [However,] I think Dr. Tull’s keynote speech and the panelists really addressed everyone.

 

To close the day, there was a career fair composed of several industry sponsors plus a few departments and campus resource centers. The room felt lively with conversation but I couldn’t help but notice the lack of diversity in the organizations attending – nearly all were engineering-based. I don’t happen to be personally interested in working in industry (although I did stop by the US Army Corps of Engineers booth to say hello since my dad and uncle worked for them for forty years) so I gravitated towards speaking with the representatives from the departments and resource centers. I mostly spent time speaking with the wonderful Nicole Rabaud, the Director of Graduate Academic Programs for the College of Biological Sciences. We spoke for nearly an hour about the state of graduate education (and more specifically my biophysics graduate group) and pathways for influence and reform. A few important reminders inspired by our conversation: (1) there are several exciting science policy fellowships opportunities in Sacramento including CCST and Capital Fellows, (2) Aggie Compass is available 24/7 for helping meet your basic needs, and (3) A “Buy Nothing” Facebook group exists for the Davis area. 

 

Me: Will you be doing it again next year? If so, what will you be changing?

Alexus: Yes, we are meeting [soon] to talk about next steps and plans for next year. We are looking to make DISC an actual organization. Having people focused just on DISC will be good. This year, we had the presidents of all of the organizations that were involved be the representatives on the committee. I was with ESTEME and also [focusing] on DISC as well, which means that often something else had to go. It’s not like we could drop off [the responsibility to] our clubs. So, for me, that was my research sometimes.

 

Overall, I really enjoyed the day and I look forward to attending this event next year. The DISC conference is a great celebration of the diversity of people in STEM at UC Davis and an important reminder about the value of community.

 

*There was a substitution not indicated on the website in the first panel of Blen Kelleni for Gwladys Keubon.

COVID-19: Keep Calm and Watch the Data

Written By: Ellen Osborn

Edited By: Jennifer Baily

 

Considering the massive media fever surrounding the current coronavirus outbreak, it might come as a surprise that most people are infected by one, if not multiple, coronaviruses during their lifetime. However, the current coronavirus outbreak is much more than just another flu.

Coronaviruses are a large family of viruses, of which several members cause mild to moderate upper-respiratory tract illnesses in humans, which account for 10% to 30% of these types of infections in adults. These endemic human coronaviruses (HCoVs) are considered inconsequential pathogens incapable of causing global epidemics. Until the early 2000s, HCoVs received little attention. 

Figure 1: The recent outbreaks of coronavirus-caused diseases known to infect humans (COVID-19 numbers are confirmed and as reported by China).

This changed when two novel coronaviruses (nCoVs) jumped from their animal reservoirs into humans and caused the Severe Acute Respiratory Syndrome (SARS) outbreak in 2002 and then Middle East Respiratory Syndrome (MERS) outbreak in 2012. Together, the SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-CoV) resulted in over ten thousand confirmed cases and 1640 deaths. The international panic brought about by these coronavirus outbreaks was crippling. In response, the World Health Organization (WHO) placed SARS-CoV and MERS-CoV on its Priority Pathogen list in an effort to galvanize research into nCoV biology as well as providing countermeasures to contain future outbreaks. 

Just two years later, an outbreak of an nCoV began in Wuhan, China. This nCoV is officially named SARS-CoV-2 due to preliminary analyses that identified genetic similarities to the 2002 SARS-CoV. Because the official name references SARS, the WHO shortly began referring to the virus as “the virus responsible for coronavirus disease 2019 ,” or COVID-19, in order to prevent unnecessary panic in populations affected by the 2002 SARS outbreak. 

The strong similarities between the COVID-19 coronavirus and SARS-CoV will undoubtedly assist in preventing and treating COVID-19. However, coronaviruses remain one of the least understood family of viruses due to their exceptionally large genome and proteome, and as a consequence, the complexity of the virus’ interactions with hosts. Here at the University of California, Davis, the California National Primate Research Center and Center for Immunology and Infection Diseases are working to establish a rhesus macaque model of COVID-19, which will be fundamental in understanding viral dissemination and age-related differences in COVID-19 disease progression. Additionally, the Interdisciplinary Research & Strategic Initiatives division of the Office of Research is coordinating the campus’ response to COVID-19 research funding opportunities and established the UC Davis COVID-19 Research Working Group to enable efficient sharing of resources, information, and to connect potential collaborates across UC Davis.

As an average news consumer, it has been difficult to pinpoint the exact level of concern COVID-19 merits. At the beginning of March, the WHO recorded 127 cases of COVID-19 in the United States – nine of which were fatal – and that community spread was beginning to occur in several locations. The CDC also received heavy blowback for an uncharacteristically slow response and subsequent release of a faulty test kit. Is the United States destined for an uncontrolled spread of coronavirus? Some are saying no and point to a more encouraging trend emerging from China in recent weeks. Dr. Bruce Aylward, an expert from the WHO, recently returned from a two-week trip to China to assess the state of the coronavirus outbreak after the country’s initial response garnered a storm of anger from its citizens and the rest of the world and relayed optimistic data. At the end of January, China was diagnosing over 2000 new cases per day with 31 provinces on red alert, but by early March, there were less than 100 new cases per day with 24 provinces down to yellow or green alert. Dr. Aylward says that this data is a good sign, and that with appropriate government-sanctioned public health measures and public cooperation, COVID-19 can still be contained globally, despite less than encouraging initial government responses.

Other world leaders and health professionals are suspect of China’s severe approach to contain COVID-19, questioning the effectiveness of essentially putting hundreds of millions of people, regardless of their health, on house arrest. Michael T. Osterholm, director of the Center of Infectious Disease Research and Policy at the University of Minnesota, wrote in a recent New York Times op-ed that although China did a remarkable job of slowing the progress of the outbreak, he is not convinced that it is sustainable and asks what others are asking: did the Chinese actually contain the virus, or have they just suppressed it? Only time will tell whether the virus will continue to spread when the Chinese people return to work and school. Even if the virus was successfully contained, it is hard to believe that China’s cordon sanitaire* could be reproducible in other countries that do not have the same surveillance infrastructure as China and whose citizens are not accustomed to authoritative government action.

Though the data are incomplete and public health measures in the United States have yet to be fully formed and delivered, it seems fair to say that social distancing is essential to contain COVID-19. Containment might require people to make sacrifices they are unaccustomed to, like working from home and canceling social events, but these are ultimately small sacrifices in the face of a global pandemic. In the meantime, instead of trying to gauge how concerned we should be from the headlines, it might be better to take the advice of New York Times reporter Donald McNield who has covered disease outbreaks since 2002: “don’t panic; watch the data.” As graduate students, we are uniquely qualified to practice this advice and communicate the data to our community.

Figure 2: Check Financial Times for the live version of this figure.

For our UC Davis readers, find campus updates here.

California state updates can be found here

CDC updates can be found here

WHO updates can be found here

 

Resources: 

The WHO daily situation reports. 

Cohen, J.; Powderly, WG. Infectious diseases. 2nd edn.. Mosby; New York: 2004.

de Wilde, Adriaan H., et al. “Host factors in coronavirus replication.” Roles of Host Gene and Non-coding RNA Expression in Virus Infection. Springer, Cham, 2017. 1-42.

de Wit, Emmie, et al. “SARS and MERS: recent insights into emerging coronaviruses.” Nature Reviews Microbiology 14.8 (2016): 523.

Li, Yan‐Chao, Wan‐Zhu Bai, and Tsutomu Hashikawa. “The neuroinvasive potential of SARS‐CoV2 may be at least partially responsible for the respiratory failure of COVID‐19 patients.” Journal of Medical Virology (2020).

Paules, Catharine I., Hilary D. Marston, and Anthony S. Fauci. “Coronavirus infections—more than just the common cold.” Jama 323.8 (2020): 707-708.

*A cordon sanitaire is the establishment of a quarantine zone where both sick and healthy people are not allowed to leave. 

The Science Behind Going Keto

Written By: Ross Wohlgemuth

Edited By: Sydney Wyatt

 

In the plethora of dieting options out there, it can be difficult to find the right one for you; sticking with it and seeing the results weeks or months later can be even more challenging. Whether it’s a traditional low-fat diet (LFD) or something more complex like intermittent fasting, each eating regime has its pros and cons that apply to different types of people with different goals in mind. Often, people choose the wrong diet or fail to stick with it, and do not reach their perceived goals. In worse cases, people may develop or worsen eating disorders by following strict diets. There is also a lot of misinformation about dieting, so it would be a shame if your 2020 resolution centered around a diet that has no scientific backing. Whatever the case may be, finding the right diet and sticking with it should be done with medical supervision.

Fig. 1. Sample ketogenic diet macronutrient proportions. This differs from the USDA recommendation by a large amount, especially in the carbohydrate category. Image from [3].

One diet in particular that is popular for weight loss and athletic performance is the ketogenic diet (KD, keto). The KD is similar to many diets in that it cuts carbs, almost to zero. While the USDA recommends that 45-60% of calories come from carbohydrates [1], the KD suggests less than 50g [2]. The macronutrient deficit is made up by an increase in fats, which make up around 70% of the caloric intake on keto [2].

The basis of the KD is that when your carbohydrate intake is low, your body can adapt by producing a new energy source called ketone bodies (KBs) [4]. KBs are made by mitochondria in the liver from fatty acid derived acetyl-CoA, and circulate throughout the body and even cross the blood-brain barrier to provide a source of energy to your cells [4,5] (Figure 2). Thus, even without consuming the recommended amount of carbohydrates, your body can still function just fine by running on fats—for the most part. The jury isn’t out on keto just yet, as some doctors and health organizations are still hesitant to proclaim as a safe way to eat.

For most people, one of the biggest factors in choosing a diet is how effective it is at promoting weight loss. In the case of the KD, science seems to support its weight loss promotion. In a meta-analysis [6] on thirteen studies involving long-term weight loss on a KD or a LFD, it found that five of the parameters tested differed between the KD and LFD groups, one of them being weight loss. They found that the average weight loss of the KD groups was 2 pounds more than that of the LFD groups. The study also found KD groups experienced decreases in blood triglycerides and diastolic blood pressure and increases in both high-density and low-density cholesterol (HDL, LDL).

Fig. 2. Schematic of ketone body (KB) formation. 3-Hydroxybutyrate, a KB, is produced from the oxidation of fatty acids, resulting in the production of acetyl CoA. Acetyl CoA is consequently converted into HMG-CoA and then to acetoacetate which is the precursor to 3-hydroxybutyrate. Figure and caption adapted from [5].

At first glance, this seems like a solid win for the KD since 3 out of the 5 changes are considered to represent indicators of health, but there are limitations to these studies to consider. The studies took place over a year or longer, and the provided counseling from a dietician varied between studies. In addition, participants were obese individuals with a mean age between 40 and 60. Further, the amount of carbohydrate intake per day by each participant was only reported to be in the keto range of 50g or less in one of the studies; the other studies either had a greater caloric proportion allocated to carbohydrates, or the value was not reported. Even greater concern is the high participant drop-out rate (15-85%) from the studies. This variation makes it hard to trust these studies, and the KD regime in general. Ultimately, the 2 pound difference between the keto and low-fat diets over a year’s time is not that much of a change, even if it is statistically significant. Thus, even though this study attempts to demonstrate that the KD is more effective in producing weight loss than the traditional LFD, there is still much to question as to the ability of participants to stay on the diet, and the relevancy of the results to a younger or more fit population.

Another factor to consider when choosing a diet is whether it improves your physical fitness or athletic performance. Under the scrutiny of scientific investigation, it seems that the KD may only benefit athleticism in certain cases. In a pilot study of five endurance athletes (four female and one male) between the ages of 49-55, a KD was maintained over 10 weeks of each athlete’s typical training schedule, consisting of 6-12 hours per week of cycling or running [7]. The athletes were tested for body composition and athletic ability at the end of the period, and were also asked to give commentary about the experiences they felt during their time on the diet.

Fig. 3. Weight loss, time to exhaustion (TTE), and ventilatory threshold (VT2) in endurance athletes from [6].

The researchers found that the body composition of the athletes improved significantly, with an average weight loss of almost 9 pounds and a significant loss in fat mass as measured through several skin folds (Figure 3). This positive weight loss was not accompanied by positive results in performance however, with declines in VO2 Max, peak power, and ventilatory threshold (Figure 3). Some athletes even reported negative experiences toward the beginning of the study, including complaints of fatigue or irritability, however, there were more positive experiences reported like feeling healthier or enjoying the weight loss by the end.

The researchers concluded that although the KD was effective in improving body composition and weight, it was not successful in improving endurance performance. They hypothesized that the lack of athletic improvement was due to lower rates of glycogenic metabolism (metabolism which uses glucose as the primary substrate), which could hinder performance in high intensity exercise. This could be due to lower blood insulin downregulating pyruvate dehydrogenase, an enzyme necessary in linking the glycolytic pathway in the cytosol to the Krebs cycle in the mitochondria [8]. The researchers also thought that liver glycogenolysis (breakdown of glycogen) could be influenced by dietary intake of carbs while gluconeogenesis (the process of making new glucose from lactate, glycerol, and other substrates) remained constant during KD [9]. Whatever the case may be, it seems that using KBs as a metabolic substrate attenuates the athletic ability of the endurance athletes in maximal intensity efforts.

In another study that compared the effects of the KD and traditional western diet (WD) on strength performance in nine elite male gymnasts around the age of 21 [10], researchers found that 30 days of the KD produced better changes in body composition than the WD, but not in strength or performance. Since the athlete’s training regimes were consistent throughout the year, each participant was able to undergo 30 days of the KD and 30 days of the WD in order to pair the two treatments for comparison (a 3 month gap was used between the two dieting periods). The results showed that 30 days of the KD led to an average weight loss of 3.5 lbs and a fat mass reduction of 4.2 lbs. This translates to a change in body fat percentage of 2.6% and an increase in lean mass percentage by a similar degree. Nevertheless, these underlying changes in body composition did not affect the athlete’s muscle mass or their athletic ability. There were no significant changes in either parameters after the KD or WD regimes. The investigators attributed the weight loss to fullness from adequate protein consumption, a greater ratio of fat breakdown to fat synthesis, lowered resting respiratory exchange ratio (meaning the predominant fuel during rest was fat), and elevated metabolism from gluconeogenesis and the thermic effect of proteins [11]. They also stated that increasing muscle mass during the KD is difficult since blood insulin levels are so low, which attenuates the muscle growth pathway via IGF-1, mTOR, and AKT (Figure 4) [12]. Thus, maintaining muscle mass during the KD is a more reasonable and attainable goal than gaining mass. With that in mind, the relevance of the KD to athletic performance becomes more important to athletes whose sport involves weight classes such as boxing. Competitors who desire to maintain muscle mass and strength while trying to lose fat to fit into a lower weight class may reasonably benefit from short term use of the KD. With this in mind, the KD seems like a reasonable option for a specific niche of athletes who may stand to gain (or lose) from periodic keto use.

Fig. 4. The signaling pathway for muscle hypertrophy relies on insulin and IGF-1 signaling, which leads to the increase in phosphorylation of AKT and the activation of mTOR. mTOR activation leads to downstream effects ultimately resulting in muscle hypertrophy (muscle growth). Figure taken and caption adapted from [12].

After looking at the KD as a weight loss promoter and performance enhancer, it certainly has its fair share of pros and cons. As far as diet commitment, the KD seems to be difficult in the first few weeks but easier as it continues. Not only were there great proportions of participants who dropped out from the studies involved in the meta-analysis, but the experiences reported from the endurance study show that the KD can be difficult and perhaps even miserable in the beginning. In addition, the carbohydrate caloric contents of the studies in the meta-analysis were not even low enough to be considered “keto” by the latter two studies addressed [7,10], so adherence to the KD by non-athletes or those who have less dietary or physical motivation may be called into question.

In the studies on endurance and strength athletes, the net carbs consumed per day were well below the 50g mark, with around 10-35g in the endurance study and 22g in the strength one. These bode well with the body composition and weight loss observed in the short amount of time the KD was followed compared to the long-term studies in the meta-analysis. Even though the meta-analysis showed that the KD had better weight loss effects than the LFD, the amount of weight lost in the 12-month period was unimpressive compared to the short-term studies. This may have to do with the demographics of each population, as the long-term studies were done on older, obese individuals and the short ones done on active people of various ages. This highlights the confounding effect of lifestyle and level of exercise to dietary studies of the KD. It is virtually undeniable that diet and exercise are the cornerstones of weight loss programs, and the combination is more effective than either alone.

The KD presents some promise to those looking to lose weight who are also generally active on a weekly basis. Although it may not be useful in improving athletic performance, it is remarkably beneficial to metabolic health when used safely and correctly. Again, any new diet program you want to try should be discussed thoroughly with a qualified physician or dietician. Given the scientific literature on the KD, I would say KD shows promise for a certain niche of people who are focused on losing weight.

Citations

  1. Dietary Guidelines for Americans. 2010. USDA, USDHHS.
  2. Gunnars, Kris. (04 January 2019). 5 Most Common Low-Carb Mistakes (And How to Avoid Them). Healthline.com 
  3. Ketogenic diet breakdown. Perfectketo.com
  4. Pinckaers, P.J.M., Churchward-Venne, T.A., Bailey, D., van Loon, L.J.C. (2017) Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype? Sports Med. 47:383-391. doi:10.1007/s40279-016-0577-y
  5. Watanabe, Shaw & Hirakawa, Azusa & Aoe, Seiichiro & Fukuda, Kazunori & Muneta, Tetsuo. (2016). Basic Ketone Engine and Booster Glucose Engine for Energy Production. Diabetes Research – Open Journal. 2. 14-23. 10.17140/DROJ-2-125.
  6. Bueno, Nassib Bezerra, et al. “Very-Low-Carbohydrate Ketogenic Diet v. Low-Fat Diet for Long-Term Weight Loss: a Meta-Analysis of Randomised Controlled Trials.” British Journal of Nutrition, vol. 110, no. 7, 2013, pp. 1178–1187., doi:10.1017/S0007114513000548.
  7. Zinn, C., Wood, M., Williden, M., Chatterton, S., Maunder, E. (2017) Ketogenic diet benefits body composition and well-being but not performance in a pilot case study of New Zealand endurance athletes. Journal of the International Society of Sports Nutrition. 14(22) doi:10.1186/s12970-017-0180-0
  8. Peters, S.J., LeBlanc, P.J. (2004) Metabolic aspects of low carbohydrate diets and exercise. Nutrition and Metabolism. 1(1):7. doi: 10.1186/1743-7075-1-7.
  9. Webster, C.C., et. al. (2016) Gluconeogenesis during endurance exercise in cyclists habituated to a long-term low carbohydrate high-fat diet. The Journal of Physiology. 594(15): 4389-4405. doi:10.1113/JP271934.
  10. Paoli, A., Grimaldi, K., D’Agostino, D., Cenci, L., Moro, T., Bianco, A., Palma, A. (2012) Ketogenic diet does not affect strength performance in elite artistic gymnasts. Journal of the Society of Sports Nutrition. 9(34)
  11. Paoli A., Canato M., Toniolo L., Bargossi A.M., Neri M., Mediati M., Alesso D., Sanna G., Grimaldi K.A., Fazzari A.L., Bianco A. (2011) The ketogenic diet: an underappreciated therapeutic option? La Clinica Terapeutica. 162:e145–e153.
  12.  Egerman, M.A., Glass, D.J. (2014) Signaling pathways controlling skeletal muscle mass. Crit Rev Biochem Mol Biol. 49(1): 59-68. doi:10.3109/10409238.2013.857291

 

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