A Stressful Situation

by  Saksham Vashistha

Affecting nearly 80% of Americans, stress has become an integral part of our communities. However, while stress can affect our mental health, cells, too, experience physical stresses. However, while stress can affect our mood, physical stresses affect our bodies at the cellular level. Getting to the bottom of how cells respond to stresses is a useful tool in a wide variety of fields. Dr. Mike Gustin, a professor of biological sciences at Rice University, aims to understand stress responses in cells and their role in the treatment of cancer.

Dr. Michael Gustin’s passion for cellular biology developed during his time as a graduate student. While working in the Ching Kung lab at the University of Wisconsin-Madison, then-physiologist Dr. Gustin and his team were the first to discover that ion channels, special proteins that span the cellular membrane and help transport charged particles into and out of the cell, exist in yeast and bacteria. Now at Rice University, Dr. Gustin has made the transition to genetics, focusing on the impact of stress on cellular behaviors. His most recent works include collaborations with researchers across the Houston area, namely Dr. Erik Cressman, a chemist at MD Anderson. 

Dr. Gustin and Dr. Cressman worked together on an NIH funded project that investigates ways to treat liver cancer. Unfortunately, as Dr. Gustin points out, “for liver cancer, there is no good chemotherapy.” Oftentimes, cancerous tumors in the liver are inoperable and alternative treatments are required. However, Gustin and his team have found that “chemistry-driven exothermic reactions (heat-generating reactions) can ablate (remove) tissues in an increasingly controlled way.” There are a variety of different reactions that can be used to ablate cells. Dr. Gustin’s group decided to use a reaction between an acid and a base. By mixing the two solutions on the cell’s surface and allowing them to react, heat and a high solute concentration (osmolarity) are produced. This extreme heat combined with the high osmolarity is toxic to the cell and kills it.

As Dr. Gustin explains, “there is an ablation zone [on the cell’s surface] where the temperature is high enough to kill cells and there is a combination of not just heat, but also high osmolarity because of the salt that accumulates there.” Gustin’s group is interested in the peri-ablation zone, the area just around the region of high osmolarity.  It was hypothesized that the applied cellular stresses are followed by some types of cellular defense mechanisms or signaling pathways. These signaling pathways serve to protect the cell from physiological stresses, helping it survive the harsh ablation conditions. Understanding how these pathways work is key for ablation treatment in cancer patients. The goal is, as Dr. Gustin says, “to inhibit those pathways in a controlled way [to] control how much ablation actually happens.” Thus, by inhibiting certain cellular defense mechanisms, ablation in cancer cells can be modulated and used precisely during cancer treatment. 

One of the interesting finds during their investigation was that sometimes the stress applied to the cells prevented the cells from even responding. Upon further investigation, it was found that some of the genes that are activated for the stress response actually inhibited other stress responses. Dr. Gustin’s team attempted to understand these stress responses at the molecular level. By using computer modeling of known proteins that were involved in the stress response pathways, they were able to identify how the structures of the proteins were changed by the cellular stresses. Gustin’s team wanted to understand “what happens to the fluid around a protein and what happens when stresses combine around that protein.” Understanding what happens to the fluid around the protein can indicate what environmental changes the protein is experiencing. The alteration of the fluid condition can lead to altered protein structures. Changes in the molecular structure of proteins affects the cell’s ability to react properly to stress. This is because the structure of the protein is what determines its function. If the structure is altered in any way, the protein wouldn’t be able to carry out its function correctly. This molecular modeling approach can help scientists understand not only at the cellular but also the tissue and organ level of how stress responses operate in a mammalian body. Furthermore, ablation in tumor cells can be controlled via inhibition of the genes and subsequent proteins involved in the cellular stress response. This control over the cell’s genes can help make ablation more effective for liver cancer patients with inoperable tumors. 

Dr. Gustin’s investigation into harnessing the power of cellular stresses has the potential to change how physicians approach the treatment of cancer. By identifying mechanisms by which cancer cells resist ablation, Gustin’s work provides new insight into how physicians can directly alter cellular defense mechanisms to make them more vulnerable to treatment. While understanding the influences of stress on cells has made significant contributions in medicine, Gustin’s work can also have applications in other fields. Dr. Gustin has his eyes set on something greater. “I am really curious about … what happens during coral reef bleaching”, Dr. Gustin says with a glint in his eyes. Coral reef bleaching is a direct result of stresses (changing water temperatures) on the cells of the organism, causing them to lose the algae living in them. The algae are responsible for providing the majority of the coral’s energy, without them the coral starve and die.  Gustin hopes to use his knowledge of cellular stresses to “genetically engineer algae that stay in the coral” reagrdless of the water temperature in an effort to save an inumerable amount of coral around the world. Such an effort would help lead the effort to rebuild important coral reef ecosystems globally.

[1] Saad, L. Eight in 10 Americans Afflicted by Stress. https://news.gallup.com/poll/224336/eight-americans-afflicted-stress.aspx

[2] Fuentes, D.; Muñoz, N. M.; Guo, C.; Polak, U.; Minhaj, A. A.; Allen, W. J.; Gustin, M. C.; Cressman, E. N. K. A Molecular Dynamics Approach towards Evaluating Osmotic and Thermal Stress in the Extracellular Environment. International Journal of Hyperthermia2018, 35 (1), 559–567.

More Than Meets the Mask: The Controversy of Face Masks in the COVID-19 Pandemic

by Vincent Lai

In a matter of months, the world has been overtaken by the coronavirus disease 2019 (COVID-19) pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, spreads from person to person through droplets or direct contact and can cause symptoms including cough, fever, muscle pain, difficulty breathing, and even pneumonia [1]. Furthermore, asymptomatic carriers help spread the virus even more effectively because they can still infect others despite showing no symptoms [1]. The many challenges people must face during the COVID-19 pandemic include loneliness, financial burdens, and bereavement [2]. To cope, the world has drastically changed. Hand sanitizer dispensers are stationed at nearly every wall. Hugs and handshakes are relics of the past. Pulling on a face mask before leaving the house has become second nature.. Although face masks have been recommended as a protective measure against COVID-19, their use has been met with considerable controversy, especially in the United States [3]. To protect the general public during the pandemic, we must consider the effectiveness of face masks, the specific reasons that make them so controversial, and ways to increase the public’s willingness to wear face masks.

One of the reasons that face masks are so controversial is because of the belief that they are not effective in reducing or preventing the spread of COVID-19. However, researchers have found preliminary evidence to suggest that this may not be the case. For example, when using model simulations of New York, Eikenberry et al. (2020) found that an 80% adoption of moderately-effective masks had the potential to prevent 17-45% of projected deaths over two months as well as decrease the daily death rate by 34-58% [4]. Researchers have also looked beyond models to find evidence for the effectiveness of face masks. In a study looking at the relationships between mask-wearing and COVID-19 cases in different areas, Cheng et al. (2020) compared the Hong Kong Special Administrative Region (HKSAR), which practices community-wide mask-wearing, with countries such as the United States (U.S.) where mask-wearing was not widely adopted in the community at the time of the study [5]. They found that the incidence of COVID-19 in HKSR was lower than that of Spain, Italy, Germany, France, the U.S., and the United Kingdom (U.K.) [5]. By preventing the spread of COVID-19, face masks have the potential to slow infection rates and prevent deaths.

With evidence that face masks are effective in helping control the spread of COVID-19, their ineffectiveness is not sufficient to explain the controversy surrounding face masks. Researchers have identified a number of other potential reasons that people may object to wearing face masks. One of these reasons is physical discomfort—specifically, headaches and adverse skin reactions such as dry skin, itching, and rashes can result from wearing face masks for prolonged periods of time [6,7]. Additional, psychological reasons also exist as Scheid, Lupien, Ford, and West (2020) describe how face masks threaten three things: people’s sense of freedom, their need to relate to others, and their ability to control their circumstances [3]. Specifically, face masks may cause people to feel that their freedoms are restricted and create divisions between people of different opinions towards mask-wearing, which can be exacerbated by mixed messages regarding mask-wearing [3]. Face masks may also hinder forming empathetic connections since they cover the mouth, which is important for recognizing emotions [8]. The importance of the mouth in emotion recognition was supported by a study where participants were instructed to assign emotions to covered faces that were sequentially unmasked, where Wegrzyn et al. (2017) found that the parts of the face that were most important for recognizing emotion were the eye and mouth regions [8]. Finally, compliance with mask-wearing may also be influenced by people’s trust in the government, and people who do not trust their government may be less likely to wear masks [9, 10]. In a study looking at data from the 2014 Taiwan Social Change Survey, Chuang et al. (2015) found that respondents who reported having higher general trust in their government were more likely to have the intention to wear a face mask when encountering a potential influenza pandemic [10]. 

Despite the many reasons that lead people to oppose mask-wearing, people must comply with mask-wearing mandates and policies to protect themselves and others from COVID-19. One way to increase compliance is to establish a mandatory mask-wearing policy rather than a voluntary one. In a study looking at German participants, Betsch et al. (2020) found that a mandatory mask-wearing policy increased compliance despite not being highly accepted and that mask-wearing was related to other protective behaviors such as physically distancing from others, handwashing, and avoiding handshakes [11]. They also found that a voluntary policy was associated with less compliance because the policy was seen as unfair since some people may comply while others may not [11]. Furthermore, a voluntary policy could increase the stigmatization associated with not wearing a face mask, which could potentially lead to further polarization and conflict [11]. Meanwhile, a widespread mandatory policy may help establish mask-wearing as a social norm. In fact, Olivera-La Rosa et al. (2020) found that during the COVID-19 pandemic, people found masked faces more trustworthy and more socially desirable than the same unmasked faces [12]. Following a mask-wearing norm may also decrease anxiety related to wearing masks [13]. In a study of Japanese participants, Nakayachi et al. (2020) found that  Finally, mask-wearing should be used in addition to other practices such as physically distancing to maximize its effectiveness in helping control the spread of COVID-19 [4]. 

Looking forward, efforts should be directed at increasing compliance to mask-wearing policies. Progress has already been made; in January of 2021, U.S. President Joseph Biden issued orders requiring mask-wearing on public transportation and on federal property [14, 15]. However, there is still much more work to be done. As of March 2021, a number of states have stopped requiring masks [16]. Among these states are Texas and Mississippi, where Governors Greg Abbott and Tate Reeves respectively have ended mandates requiring their states’ residents to wear face masks, citing declining cases and the increasing availability of COVID-19 vaccines [16]. These decisions may put even more people in danger and reverse the progress that has been made. To prevent even more deaths from COVID-19, state and local governments must instead endorse policies that protect people from the virus, including mask mandates. Businesses should also continue to enforce their own protective policies, including mask-wearing and physical distancing, to protect their employees and customers while reconsidering serving those who do not comply with their policies. 

References

[1] Lai, C., Shih, T., Ko, W., Tang, H., Hsueh, P. Int. J. Antimicrob. Agents. 2020, 55, 105924. 

[2] Marmarosh, C. L., Forsyth, D. R., Strauss, B., Burlingame, G. M. Group Dyn. Theory Res. Pract. 2020, 24, 122-138.

[3] Scheid, J. L., Lupien, S. P., Ford, G. S., West, S. L. Int. J. Environ. Res. Public Health. 2020, 17, 6655.

[4] Eikenberry, S. E., Mancuso, M., Iboi, E., Phan, T., Eikenberry, K., Kuang, Y., Kostelich, E., Gumel, A. B. Infect. Dis. Model. 2020, 5, 293-308.

[5] Cheng, V. C., Wong, S., Chuang, V. W., So, S. Y., Chen, J. H., Sridhar, S., To, K. K., Chan, J. F., Hung, I. F., Ho, P., Yuen, K. J. Infect. 2020, 81, 107-114.

[6] Lim, E. C. H., Seet, R. C. S., Lee, K.-H., Wilder-Smith, E. P. V., Chuah, B. Y. S., Ong, B. K. C. Acta Neurol. Scand. 2020, 113, 199-202.

[7] Hu, K., Fan, J., Li, X., Gou, X., Li, X., Zhou, X. Medicine (Baltimore). 2020, 99.

[8] Wegrzyn, M., Vogt, M., Kireclioglu, B., Schneider, J., Kissler, J. PLoS ONE. 2017, 12.

[9] Condon, B. J., Sinha, T. Health Policy. 2010, 95, 50-56.

[10] Chuang, Y., Huang, Y., Tseng, K., Yen, C., Yang, L. PLoS ONE. 2015, 10, e0122970.

[11] Betsch, C., Korn, L., Sprengholz, P., Felgendreff, L., Eitze, S., Schmid, P., and Böhm, R. Proc. Natl. Acad. Sci. U.S.A. 2020, 117, 21851-21853.

[12] Olivera-La Rosa, A., Chuquichambi, E. G., Ingram, G. P. D. Pers. Individ. Differ. 2020, 166, 110200.

[13] Nakayachi, K., Ozaki, T., Shibata, Y., Yokoi, R. Front. Psychol. 2020, 11, 1918.

[14] The White House. https://www.whitehouse.gov/briefing-room/presidential-actions/
2021/01/20/executive-order-protecting-the-federal-workforce-and-requiring-mask-wearing/ (accessed Feb. 10, 2021).

[15] The White House. https://www.whitehouse.gov/briefing-room/presidential-actions/
2021/01/21/executive-order-promoting-covid-19-safety-in-domestic-and-international-travel/ (accessed Feb. 10, 2021).

[16] Shammas, B.; Wan, W.; Fowler, S.; Moravec, E. ‘Masks required’ signs are coming down after Texas, Mississippi lift coronavirus restrictions. The Washington Post, Mar 4, 2021. https://www.washingtonpost.com/health/2021/03/03/texas-mississippi-covid-restrictions-masks/ (accessed Mar 7, 2021).