Davis Downfall According to Sierra Club
By Mari Hoffman
Authors note: UC Davis does an immense amount of waste reduction and energy conservation practices, but after writing this essay in my Water Quality at Risk class I wondered if it is enough. In 2018, UC Davis did not make it on the “Cool Schools” list by Sierra Club Magazine. The previous year we were ranked as number 32. I was assigned this essay to compare some of the practices that UC Davis does with other schools to get an understanding on what we are excelling at and where we can improve. I chose to focus on how we can improve in regards to water waste with an implementation of porous concrete.
A Regenerative Cocktail: Combination of Drugs Promotes the Conversion of Glial Cells to Neurons
By Reshma Kolala, Biochemistry & Molecular Biology ‘22
Author’s Note: While browsing recent findings in Neuroscience, I came across research investigating the possible conversion of glia to neurons. Although the conventional idea that neurons are irreplaceable has been overturned in multiple research studies, I was immediately intrigued by the possibility for neighboring glia to be the source of neural regeneration. The implications of this research could completely transform how treatment is approached in the neuroscience field of medicine.
This is Your Brain on Music
By Timur Katsnelson, Neurobiology, Physiology, and Behavior, ‘19
Author’s Note: Like everyone else, I love music- especially the works of my favorite artists. There is nothing better than listening or jamming out to your favorite song. The human love for music is a powerful binding force, but why do we even like it? What are the underlying physiological responses of our enjoyment? I wanted to explore the functions of our brain as they relate to enjoying music, and found some interesting results about what scientists have uncovered thus far.
One of the most distinguishing characteristics of the human brain is the ability to interpret and feel emotions regarding complex environmental stimuli such as visual arts and music. Even more interesting is the seemingly infinite amount of variation in how each individual perceives these stimuli, or rather, the reason why one person may love to listen to Vampire Weekend while another casually listens to a lo-fi playlist. There are structural similarities shared by all humans, crafted over millions of years of evolution, but they do not account for different tastes. Neuroscientists who study dopaminergic pathways and other neural structural mechanisms have made several initial steps in understanding what physiological functions music serves to humans. So far, it has been established that musical appreciation and preference are related to the connectivity of white matter between regions in the auditory cortex and the regions processing emotion; variations in activity from neurons related to emotional communication could explain our differences in musical taste. Answering questions about the effects of music on the brain will undoubtedly help to answer larger questions about music’s evolutionary purpose and its profound impact on human cultures.
Neuroscience of Pleasure and Reward
Motivation, emotion, and arousal can all be attributed to elevated activity in the reward centers of the brain. As these traits are known to have implications in addiction, their cellular manifestations have been studied for several decades. The ventral striatum, midbrain, amygdala, and some areas of the prefrontal cortex have all been demonstrated, in varying degrees, to being recruited in instances of drug use. The dopaminergic pathways of the brain refer to a series of densely-packed neuronal connections that are stimulated by the neurotransmitter dopamine to propagate signals. Collectively, these regions of the brain are responsible for our response to natural stimuli and our actions to either seek or avoid them.
The brain’s reward centers are also known to be active in communal interactions, suggesting that there is a benefit to acting in a socially-positive way. Interestingly, the emotions experienced by humans when listening to their favorite music is correlated to the engagement of the same dopaminergic pathways as those that are stimulated during drug use or social interactions. It is important to note that the similarities between which parts of the brain are engaged when listening to music, using drugs, or being with people do not imply that the physiological or psychological effects are closely mimicked in the process. Neurons communicate via action potentials. These synaptic changes in membrane voltage effectively signal messages to neighboring neurons, but nothing about them is inherently meaningful. Since all action potentials are the same, it is the frequency of their appearances that convey messages. As it relates to the similarities in regions activated by both drug use and music, increases in activity do not necessarily equal the same frequencies of action potentials. Nonetheless, positron emission tomography (PET) scans observing pleasurable responses to music in animals and humans show the same regions of the brain being activated. Increases in dopaminergic pathway activity in the nucleus accumbens (NAc), ventral pallidum, ventral tegmental area, amygdala, hippocampus, and other areas of the midbrain collectively correlate to the reward process [3].
The Brain’s Response to Music
There are several experiments that examine the neural response to music, or “aesthetic responses” as some scientific literature has described. PET studies visualized the neural relationship with ‘intensely pleasurable’ responses to music [2]. Intensely pleasurable responses are defined as euphoric sensations in reaction to music, characterized by “shivers-down-the-spine” or “chills” [1]. In addition to observing activity levels within the brain, researchers monitored heart rate and blood flow in the brain. When excited by external stimuli, the central nervous system commands a response throughout the body to heighten the senses and increase awareness. A study by Blood et al. measured heart rate and cerebral blood flow of subjects listening to chill-inducing songs. Increases in the intensity of stimulation from a song were shown to increase blood flow in areas of the brain’s reward centers, as well as the heart rate. It is known that pleasure derived from music activates regions between the brain’s auditory region, specifically the superior temporal gyrus, and the reward centers such as the ventral and dorsal striatum. Parts of the basal ganglia, the ventral and dorsal striatum are largely responsible for motor function as it relates to desire and reward. Despite these findings, the exact connection between physiological sensations and aesthetic responses in the brain are ambiguous [1].
Evolutionary Advantage?
The question of music’s evolutionary purpose has been postulated for over a century, including in Darwin’s The Descent of Man, and Selection in Relation to Sex [3]. To some experts, music is considered to be the result of an evolutionary exaptation. That is, music’s purpose was not selected for its current use by humans. Rather, it came about as a result of excited neural pathways that engage emotional responses [1]. Others suggest that music is an important communicative tool that possibly preceded speech and language [5]. In this case, the chills elicited by music are physiologically measurable emotional responses, which signify that music is effectively a resource for communicating emotions [3].
Based on this idea, some researchers wanted to examine responses to music between individuals and compare them to the structural foundations of their emotional expressiveness capacity. Musical anhedonia is used to describe a condition for those who do not exhibit any pleasure from music, as there is no dopaminergic response from the reward centers. The flat affective response of individuals with this condition could be compared to the brains of subjects with affective responses to music. One such study found that patterns of white matter networks between the superior temporal gyrus through the ventral and dorsal striatum predicted the amount of reward response elicited by music. As the name suggests, the superior temporal gyrus is part of the temporal lobe- which is associated with the auditory cortex. This path of white matter moves from the auditory processing system to the basal ganglia. The aforementioned ventral and dorsal striatum, both parts of the basal ganglia, are involved in motor function. However, there could be other reward-related responses elicited from these structures, such as chills. Some researchers postulate that music may have had its origins from chill-responses to pleasurable sounds in the evolutionary environment, which may have motivated our ancestors to create their own response-evoking sounds [3]. Chills are viewed as a form of communication, demonstrating a positive response to sounds. Therefore, finding this white matter network may suggest that, in addition to emotion, there is a structural aspect of music involved in communication [3].
Music’s Effect on Other Species
A less studied and even less understood aspect of music is its meaning and interpretation by other species. Understanding the effect of music on other animals could provide a glimpse into music’s inherent biological meaning. Although it is clear that the pleasures that humans experience from music are not necessarily akin to the experience of animals, research suggests that music genres can affect the mood or behavior of captive animals. Country music has been shown to improve the mood and well-being of cattle, as opposed to more harsh or erratic-sounding music such as rock and jazz. One study specifically showed that cows more readily entered milking parlours when exposed to country music. However, these foundational animal studies have strictly been observant of the behavior and activity of the cattle [4]. Examining the neurological differences in musical preference or indifference in cattle would provide more concrete evidence of the neurological change that leads to the observed behaviors.
Further Discussions and Research
The research discussed thus far provides clues into the baseline purposes of music and the nature of its evolutionary impact. Yet, there are still many interesting existential discussion topics surrounding the origins of music and its purpose. Grounded biological inquiry, however, will be the most essential tool to get closer to understanding the extraordinary impact of music on human culture, communication, and evolution. Moving forward, researchers should continue to address the differences between individual preference and capacity to respond to music by studying differences in neural matter and structure. Most evidence suggests that music has a strong correlation to emotional expression, so examining the mechanisms of communication and interpreting abstract stimuli as emotional cues will help researchers understand how music can be physiologically deciphered and responded to. On a broader scale, examining global differences in musicality could provide insight into how different cultures and languages relate to their historically popular forms of music and rhythms. Could phonetic or rhythmic patterns in language correspond to preferences for certain tempos, measures, rhythms, or lyrics in music? These questions would be better served in a separate discussion but for now, go back to enjoying your favorite song.
References:
- Blood, A. J., & Zatorre, R. J. (2001). Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proceedings of the National Academy of Sciences of the United States of America, 98(20), 11818-23.
- Matthew E. Sachs, Robert J. Ellis, Gottfried Schlaug, Psyche Loui (2016). Brain connectivity reflects human aesthetic responses to music, Social Cognitive and Affective Neuroscience, Volume 11, Issue 6, Pages 884–891.
- Psyche Loui et al. (2017). White Matter Correlates of musical Anhedonia: Implications for Evolution of Music. Frontiers in Psychology, Volume 8, Article 1664.
- Deborah L. Wells (2009). Sensory Stimulation as Environmental Enrichment for Captive Animals: A Review. Applied Animal Behaviour Science. Volume 118, Issues 1-2, Pages 1-11.
- Steven Mithen (2007). The Singing Neanderthals: The Origins of Music, Language, Mind, and Body.
A Forbidden Food: a Narrative about Chronic Allergy Management
By Anna Kirillova, Genetics & Genomics ’19
Author’s note: I wrote this case study for my writing in health sciences class since allergies are a growing epidemic in the developed world. Due to the prevalence of this chronic chronic condition, food contamination is health concern for those prone to acute allergic reactions. However, little is known about the etiology of immune system dysfunction and many patients are unable to receive a concrete diagnosis. I chose to interview my friend to get a glimpse into what it’s like to manage this chronic condition and to learn more about the potential causes and treatments.
CRISPR: Are We Ready For It?
By Tannavee Kumar, Genetics and Genomics, ’20
Author’s Note: When I found out that CRISPR was used for the first time on human embryos that were fully brought to term, I was pretty surprised that such a new technology with numerous unknowns was being used on the germline. I was interested in understanding the reasoning for such an experiment and what may come out of it in the long run. To some, CRISPR may seem like a far off technology that could be applied to humans in the distant future. However, the experiment on the twin fetuses that went through this “genetic surgery” proves that CRISPR is happening now and is likely to stay.
But first, how does CRISPR work?
CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats, is a genome editing technology that is cheaper, faster, more accurate, and more efficient than other existing genome editing methods [1]. The CRISPR-Cas9 system was initially adapted from the prokaryotic defense system, where CRISPRs are found in both archaea and bacteria [5]. CRISPR arrays serve as an integral part of the immune system by consisting of repeating sequences of genetic code which are interrupted by “spacer” sequences — residues of genetic code from previously attacking bacteriophages [1,5]. When the viruses attack again, the bacteria transcribe CRISPR RNAs (crRNAs) from the “spacer” regions in the CRISPR arrays to latch onto the viral DNA, where Cas9 — an enzyme that recognizes the crRNA — will cut the DNA, causing the knockout to cease the progression of the attack [5].
In the lab, the CRISPR system works in a similar manner. Researchers can also utilize various other enzymes to cleave the unwanted DNA, one such being Cpf1. Where CRISPR-Cas9 would produce blunt ends — a complex where the DNA is cut at the same location on each strand — CRISPR-Cpf1 cuts DNA at different locations, thus creating short single-stranded overhangs [5]. These overhangs, otherwise called sticky ends, can help make the insertion of new DNA more stringent, accurate, and of the correct orientation. Various enzymes also recognize different areas on the DNA; this differentiation allows researchers to allocate enzymes to their area of study [5]. Once the DNA is cut, segments of interest can be inserted or deleted by using the cell’s mechanism of homology-directed repair (HDR) and non-homologous-end joining (NHEJ) [1, 6].
Scientists hope to expand their findings pertaining to CRISPR on a variety of issues, especially single-gene disorders such as hemophilia, cystic fibrosis, and sickle cell disease. In the long term, CRISPR also shows promise in preventing or treating cancer, heart disease, mental illness, and human immunodeficiency virus (HIV) infection [1]. However, these findings and advancements in application come with various ethical concerns. As of now, most changes introduced with genome editing are limited to somatic cells. This ensures that changes are restricted to few tissues and cannot be passed down from one generation to another; however, changes made to germline cells, or even to embryos, can be passed down to future generations. Since this area is still relatively new and unknown, there is not yet enough information about the accuracy and long-lasting impact. Off-target effects could prove disastrous as there would be an entirely new set of unforeseen consequences. Moreover, even at the right target, genes interact in a complicated matter; changes at one site could have implications in a completely different area. Multiple unknowns coupled with long term consequences led to a tremendous outcry after it was revealed that two twin girls were born after having changes made at their embryonic stage.
The Trial
While He Jiankui has not published a paper describing the methodology and details on his experiment, he released a promotional video for his study on The He Lab YouTube channel on November 25, 2018. He describes how because “Mark” is HIV positive, he and his wife “Grace” were concerned that their children would potentially be positive as well [2]. This made them viable candidates for the experiment. He Jiankui mentions that along with fertilizing Grace’s egg with Mark’s sperm, the researchers also “sent a little bit of protein and instructions” that would do a “gene surgery” to remove the doorway in which HIV enters to “infect people” [2]. In the video, He claims that the team considered the surgery to be a success, as confirmed by genome sequencing [2]. Lastly, twin embryos were implanted via regular IVF “with one difference” [2].
This resulted in the first “CRISPR babies”: “Lulu” and “Nana.” He acknowledges that his actions will spark unparalleled controversy; however, he describes this path as no different than when in vitro fertilization (IVF) was first used to create Louise Joy Brown in 1977. According to the limited information published in Shenzhen HOME Women’s and Children’s Hospital ethics committee review application, mouse and monkey models were initially used to conduct “rigorous” early-test studies for the CCR5 gene since it serves as a receptor that the latches onto a white blood cell [3, 4, 7].
The next step was embryos of model organisms similar to humans were examined after going through CRISPR-Cas9 gene editing [3]. Genetically edited embryonic stem cells were isolated to determine if they abnormally propagated and whether they differentiated after genetic testing [3]. To address off-target effects, two methods were used. Firstly, using high-fidelity Cas9 enzymes, He was able increase stringency and reduce off target effects [3]. Secondly, the best single guide RNA (sgRNA) was selected for which consists of the crRNA fused to the scaffold tracrRNA sequence that Cas nuclease binds to [7]. Using these critical steps, the CCR5 region was able to be deleted.
What is Next?
According to the Associated Press, He altered the embryos of seven couples, with the birth of only Lulu and Nana so far [9, 10]. In every case, the father was infected with the disease, and the mother was HIV-negative. He’s goal was to introduce an uncommon, natural genetic variation that would make it difficult for HIV to infect white blood cells [8]. By deleting the receptor, the apparent intent was not to reduce the chance of transmission from the father, since the likelihood naturally decreases when the sperm is washed before insemination during IVF. Rather, He stated that he wanted to reduce the chance of infection later on in life [8]. While He claims that he is against gene editing for enhancement purposes and that it should only be used for therapy, many question whether his actions prove hypocritical [2]. Many assert that He’s actions suggest that being born HIV susceptible is a disease state; however, common sense tells indicates otherwise, and that the lengths that He went through to reduce HIV susceptibility are not medically justified [8, 9].
The limited information suggests that He’s editing was incomplete, and that one of the twins is mosaic [9]. This would mean that only some cells have the silenced CCR5 gene, thus indicating that there is a significant likelihood that she would not be protected from HIV [9, 10]. Even with a successful deletion all around, certain strains of HIV can still enter cells through CXCR4, a protein [9]. When geneticists first identified people with a natural genetic variation consisting of non-working copies of CCR5, it was thought that they would be resistant to HIV without any repercussions [9]. However, later studies showed that deficiency in CCR5 meant that people were more susceptible to infections like West Nile virus, Japanese encephalitis, and more likely to die from influenza [9, 11]. While CRISPR can help spearhead numerous medical advancements, there is no doubt that many unknowns remain. Unintended consequences that the twins and other potential children of this study could face would prove that the progression of CRISPR applications for humans, especially for embryos, is premature.
References
- “What Are Genome Editing and CRISPR-Cas9? – Genetics Home Reference – NIH.” U.S. National Library of Medicine, National Institutes of Health. Web.
- He, Jiankui. About Lulu and Nana: Twin Girls Born Healthy After Gene Surgery As Single-Cell Embryos. YouTube, The He Lab, 25 Nov. 2018. Video.
- He, Jiankui. “Shenzhen HOME Women’s and Children’s Hospital Medical Ethics Committee Review Application.” Chinese Clinical Trial Registry , 8 Nov. 2018.
- He, Jiankui, and Jinzhou Qin. “Chinese Trial Registry: Trial Information.” Guangdong, CHina, 8 Nov. 2018.
- “Questions and Answers about CRISPR.” Broad Institute, MIT & Harvard University , 4 Aug. 2018. Web.
- “What Is the Difference between Non-Homologous End Joining (NHEJ) and Homology-Directed Repair (HDR)?” Web.
- “Full Stack Genome Engineering.” Synthetic Guide RNA for CRISPR Genome Editing | Synthego, SYNTHEGO. Web.
- Normille, Dennis. “CRISPR Bombshell: Chinese Researcher Claims to Have Created Gene-Edited Twins.” Science | AAAS, American Association for the Advancement of Science, 27 Nov. 2018. Web.
- Yong, Ed. “A Reckless and Needless Use of Gene Editing on Human Embryos.” The Atlantic, Atlantic Media Company, 27 Nov. 2018. Web.
- Marchione, Marilynn. “Chinese Researcher Claims First Gene-Edited Babies.” AP News, Associated Press, 26 Nov. 2018. Web.
- Falcon, A., et al. “CCR5 Deficiency Predisposes to Fatal Outcome in Influenza Virus Infection.” Journal of General Virology, vol. 96, no. 8, 2015, pp. 2074–2078., doi:10.1099/vir.0.000165.
Efficacy of Various Treatments in Comparison to Surgery for Lower Back Pain Related to Disc Herniation
By Arianne Medrano, Psychology- Biology Emphasis, ‘19
Author’s Note: I wrote this literature review for my UWP 104F class in my fourth year at UC Davis. My goal is to become a physical therapist and one of the most common complaints I hear from older generations is that they cannot perform activities they once loved because of a ‘bad back.’ My father experienced a disc related injury, which led to sciatica, after he fell off a ladder. This prevents him from enjoying activities such as heavy-lifting, riding roller coasters or picking up his grandson. For these reasons, I was interested in researching effective prevention and treatments to help alleviate discomfort and improve quality of life.
Erasing Cue-Associated Memories
By Neha Madugala, Cognitive Science, ‘22
Author’s Note: While working on a different paper, I became interested in treatment and therapy for drug addiction. Addiction continues to increase, yet there seem to be limited viable options to actually overcome this problem. One of the main issues in the recovery process is relapses. I found this study interesting and promising for drug therapy because it directly targets relapses, an important step in preventing and treating drug addiction more effectively.
Are Children Fighting The “Fat” Gene? An Analysis of Pediatric Obesity and Genetics
By Peggy Palsgaard
Author’s Note: I wrote this literature review for my UWP 104F class, and I specifically chose this topic because obesity is a very stigmatized disorder or “disease” (as the AAMC recently labeled it). I wanted to explore the link to genetics and to see how thoroughly we understand the underlying causes of obesity, specifically in children. Further, the judgement of both the children and the children’s parents has brought up a conversation about whether or not it is okay to place a child into foster care for treatment of obesity, due to lack of care by the parents. Initially, research into foster care seemed out of place in this paper. However, I think it’s an interesting way to combine the scientific advancements outlined in this review paper with the social contentions surrounding obesity. I hope the reader will come away with a more thorough understanding of the complexity of the disease based on the link to genetics.
“Gut Feeling”: How Does Modulation of Gut Microbiome Affect Depression Pathophysiology and Status?
By Raida Aldosari, Nutrition Science (Biology option) ’18
Author’s Note: I wrote this literature review as part of my UWP 104F class with Dr. Lisa Sperber. The assignment was to choose a clinically-relevant topic, review the existing body of literature on this topic, and choose a specific area to write on. My topic of interest was about the relationship between gut microbiome and the brain. I became interested in this topic after reading an article about the differences between the microbial composition of individuals with depression. By the end of the quarter, my research question evolved from “how does our diet affect our brain or mood?” to “how does modulation of gut microbiome affect depression pathophysiology?” I enjoyed the flexibility of the assignment, and I greatly benefited from the guidance provided by Dr. Sperber. I would recommend this class to anyone interested in health-related fields, especially in research!