The Discovery of Feature Detectors

I recently read a classic neuroscience paper from 1959 entitled "What the frog's eye tells the frog's brain," describing the discovery of what we now call "feature detectors," or visual receptors within the retina that are sensitive only to certain kinds of visual stimuli within their receptive field. For example, one kind of feature detector could be sensitive only to moving parallel lines, while another is only sensitive to curvature through color contrast. By encoding their excitement through different patterns of action potentials, these different feature detectors enable images to be relayed to the brain through a universal language of neuronal firing -- and without the discovery of feature detectors, we may have gone on for awhile yet believing that the retina was just an amorphous conglomeration of random receptors that all fired at once, and seemingly at random. 

While this paper relates more to our week about the nervous system than this past week's lectures, I greatly enjoyed delving into this publication. If you have any interest in brain science, I would highly recommend giving it a moment of your time, because it really is an entertaining read. Though the paper's findings are fascinating within themselves (I mean, the scientists mounted frogs on corkboard, conducted neurosurgery to reveal their optic nerve, successfully recorded individual action potentials from both myelinated and unmyelinated axons, concluded that feature detectors existed, and then patched up the frogs for release into the wild), the way the paper is written is also quite marvelous from a literary standpoint. Lettvin, the first author, began his early career as a poet, then became an electrical engineer, and then turned to neuroscience to make one of the most quintessential discoveries to our understanding of the visual system to date. His background as a poet really shines through in the stylistic aspects of this paper, and I think that's perhaps what makes it so entertaining. Lettvin brings the frog to life, as if he were studying some divine being, and cracks intellectual jokes throughout the paper. Again, really worth a read! Sometimes I wonder why that sense of humor has slowly crept out of science as we read more contemporary papers. I had more fun reading this paper than most any other paper in my undergraduate career thus far, and I retained more from it due to my interest in the narrative it creates. Maybe, as the next generation of scientists and authors of scientific publications, this aspect of playfulness and engaging with readers might be something to think about. 

Here's a link to the paper pdf: What the frog's eye tells the frog's brain

Muscle Damage

After John's brief introduction of muscular functions this week, I wanted to take a bit of time to look into muscle damage, and why we get so sore after working out!

Now, it's firstly important to understand that the main perpetrator of our muscle damage and subsequent soreness is eccentric muscle action, aka movements that lengthen the muscle while applying force to them. John briefly mentioned a great example of this- running downhill. As you extend your leg forward, your quadriceps lengthen as you apply force. As he also mentioned, this is one of the times you are most injury-prone. However, the force applied to the muscle isn't the only potential cause for muscle damage. Other factors like metabolic depletion, calcium influx, or musculotendinous stiffness can contribute to or cause muscle damage during eccentric movements (Bryne et al., 2004). 

One general effect of muscle damage is a loss in isometric strength (Byrne et al., 2004). Isometric strength is required during static exercises, like planks or wall squats. It's particularly important because it also represents the strength required by your body to simply fight gravity while you're standing up. Additionally, studies have shown a decrease in dynamic strength (Byrne et al., 2004). Dynamic strength is required when a force is repeatedly applied for a period of time and is used during exercises like sprinting. 

Overall, it is important to recognize your limits and prepare yourself as best as possible to avoid muscle damage. Pay attention to your body's limits, avoid over-exercising, and give your body time to recover (also in general, stretching is great). Whether you plan on becoming an elite athlete or you just enjoy running on the weekends, just remember to stretch out and take care of your body!

Byrne, C., Twist, C., & Eston, R. (2004). Neuromuscular Function After Exercise-Induced Muscle Damage: Theoretical and Applied Implications. Sports Medicine, 34(1), 49–69. https://doi.org/10.2165/00007256-200434010-00005

Preventing Osteoporosis in Space with Melatonin

Osteoporosis is a big problem for astronauts and the future of space exploration and space missions. Instead of exercise, this research team turned to preventative medicine. They found that melatonin can be used to prevent osteoporosis in microgravity.



Melatonin was found to stimulate the mRNA expression of Calcitonin, which inhibits osteoclasts, and also decrease the mRNA expression of kB ligand, which promotes osteoclastogenesis. Osteoclasts are bone cells that absorb bone tissue during growth and healing.



My favorite part of this study lies in their creative methods. Obviously they couldn’t test on human astronauts, so they instead used the next best thing: goldfish scales. The goldfish scales spent time on the International Space Station, before returning to Florida’s Kennedy Space Center lab on Earth for analysis.



Citation:Ikegame, M, Hattori, A, Tabata, MJ, et al. 2019. Melatonin is a potential drug for the prevention of bone loss during space flight. J Pineal Res. 67(3). https://doi.org/10.1111/jpi.12594

Cocaine

Hey everyone! Since middle school I've always been a little frightened about the effects of drugs so, today I wanted to talk about the effects chronic cocaine use has on the brain.

As some background, when cocaine is snorted, smoked, or injected, it enters our bloodstream and passes through the blood brain barrier. The high from cocaine comes from the buildup of dopamine within our brains once cocaine is ingested. Dopamine is a neurotransmitter that attaches to a receptor of another cell. This all takes place in the synapse. Dopamine is responsible for the pacing of our cells, making cells work harder during periods of stress. The transfer of dopamine from neuron to neuron is regulated by receptors on the initiating neuron that pick up dopamine, preventing it from binding to the active site of neurons. Cocaine binds to these dopamine inhibitors preventing them from picking up excess dopamine. This causes more dopamine than is needed to be transmitted across the synapse to our receiving neuron.

One of the most notable effects of extended cocaine use is the alteration of gene expression in brain cells. This paper focuses on the change of expression of the protein FosB. FosB is a protein that is found in the cells of the nucleus accumbens. Interestingly, FosB plays a similar role to dopamine in that it acts as a pacer. It does this by acting as a transcription factor in the cell, controlling the expression of certain genes. Chronic cocaine use causes an increase in the amount of FosB found in the cell. Unfortunately, FosB can live up to 6-8 weeks, which means chronic cocaine use only exacerbates the high levels of FosB found in the nucleus accumbens. Furthermore, mice with increased expression of FosB exhibit addictive behavior while those that have a normal amount of FosB expression do not. This suggests that FosB plays some part from drug abuse to full blown addiction in humans.

With all this in mind, it is important to remember that reformed addicts still receive cravings for drug abuse years after their sobriety started. FosB only lasts for up to 2 months, so the likelihood of FosB to be involved in these cravings is believed to be low. There are some hypothesis as to why these cravings last for so long. One important detail is that chronic cocaine use causes nerve cells to extend and grow more offshoots in their dendrites. This could cause an increase in signals, specifically from the amygdala, hippocampus, and frontal cortex. This causes the aforementioned regions of the brain to have more influence over the nucleus accumbens. As drug associated memories are induced, the influx of messaging from the amygdala and hippocampus could be responsible for the intense cravings.

 Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851032/

Citation: Nestler E. J. (2005). The neurobiology of cocaine addiction. Science & practice perspectives, 3(1), 4–10. https://doi.org/10.1151/spp05314

Donut Brains?

We all know that octopuses and other cephalopods are among the smartest animals on the planet. My question for the week is why did their brains and nervous systems develop the way they did?

These creatures have always been some of my favorites, since they have really interesting adaptations and special features. Since we were talking about the nervous system this week, and I remembered that octopuses have donut shaped brains, I wanted to look more in depth on it.

As it turns out, the donut shaped brain is not exclusive to octopuses. It was also found that the colossal squid has a donut shaped brain, too. Why would an animal have a donut shaped brain? Great! I'm glad you asked. 

About 1/3 of the "brain" is in the donut shaped mass. The rest are distributed in ganglion throughout the octopus' arms, so technically they have nine brains. One "mini brain" (aka a large ganglion) is in each arm, and then plus the donut shaped brain in the head makes 9 brains. Another fun fact that I found was that the cephalopod's esophagus runs directly through the center of their donut shaped brain. The hole in the center isn't large, but is large enough so that the esophagus can run through it. Because of this, certain species of colossal squid are known to break their food up into tiny bits to avoid hurting their brains.

Overall, I could not find anything that says why a cephalopod may have developed this way, but I still thought it was a cool fun fact, so I kept looking into it.

After looking into cephalopod brain development a bit more, I found that the development is very complex (as to be expected) with various developmental genes and molecular processes. I have attached an article below that goes in depth on cephalopod nervous system development, and it is surprisingly well organized and not terrible to try to comprehend.

http://www.todayifoundout.com/index.php/2012/10/the-colossal-squid-has-a-doughnut-shaped-brain-with-their-esophagus-running-through-the-hole/

https://www.nhm.ac.uk/discover/octopuses-keep-surprising-us-here-are-eight-examples-how.html

https://www.frontiersin.org/articles/10.3389/fphys.2018.00952/full (article for nervous system development)

Also: my knowledge from working at an aquarium for 3 years... I'm not sure how to cite that.

Remapping The Mind: Real-Life Neuromods

Prey was an old video game that I used to play, and in it there were many sci-fi tools that could help the player progress.  The main tool of the game was called the "Neuromod", a device that injected a serum into the brain via the optic nerve and had the ability to remap someone's brain to match that of someone with a certain skill.  According to the game's lore, this Neuromod would grant the user the template organism's skill as well. Although this idea, and the subsequent abilities "learned", are outlandish and fictional, I wondered if there was any research being done in the field of remapping the brain for therapeutic purposes. I found that this idea seems to not be as outlandish as I originally thought. 
According to two papers I read, the brain is not only always changing, but these changes can be observed in different physical changes in the brain like changes in the dendritic lengths, the number of connections, and other physical changes (1).  In one experiment, monkey brains were analyzed after localized damage. It was found that, although the brain naturally starts to create new dendritic connections with time and even faster after learning a challenging new skill, localized brain damage was found to also increase new connections (1). Now, although this offers a novel way to stimulate growth and diversification of new neural connections in the brain, it does come at the cost of brain damage and the high possibility of permanent disability. However, a second paper on the neural interfaces used in high-tech prosthetics seems to offer some ways to potentially fix this issue. In this paper, BMI (brain-machine interfaces) and BoMI (body-machine interfaces) can be used to improve connections in the brain after damages to the brain and spinal cord(2). These neural interfaces allow people to recover motor skills after accidents and other cases of brain/spinal cord injuries. Now, if a way to direct and specify the fixes the brain makes was found, then these three procedures could lead to the development of something very similar to a Neuromod.

1.) Johansen-Berg, H., Structural Plasticity: Rewiring the Brain (February 2007), Current Biology (17-4), 141-144, https://doi.org/10.1016/j.cub.2006.12.022
2.)Pierella, C., et al, Remapping residual coordination for controlling assistive devices and recovering motor functions (December 2015), Neuropsychologia (79-B), 364-376, https://doi.org/10.1016/j.neuropsychologia.2015.08.024

The Woman Who Can Smell Parkinson's Disease

The super-sniffing disease-detecting dogs from lecture this week reminded me of a podcast I first listened to at the beginning of spring quarter. The podcast was on Invisibilia, from NPR, and the episode was titled “An Unlikely Superpower.” The episode presents Joy Milne, a Scottish woman who can detect Parkinson’s disease with her sense of smell. 

Milne always had a powerful sense of smell. When her husband Les was 31, she became aware that his natural scent had changed to something unappealing and foreign to her, and no amount of showering or cleaning was changing it. The scent stayed. 

14 years later, Les was diagnosed with Parkinson’s disease. When the couple walked in to a Parkinson’s support group, Joy Milne immediately noticed that the room smelled overwhelmingly like her husband’s new scent. Could Joy Milne detect the presence of Parkinson’s disease, by simply smelling people? After contacting Parkinson’s researcher Tilo Kunath, Joy took a test.

Kunath organized an experiment to test Joy’s ability, by presenting closed bags containing plain white T-shirts that were worn by either a person with Parkinson’s disease or by a control group that didn’t have the disease. Joy correctly identified 63 out of the 64 samples. The one shirt that Joy was wrong on was from the control group, and Joy had identified it as positive for Parkinson’s. Months later, the man who wore that shirt tested positive for Parkinson’s, making Joy 100% accurate in the test.

Kunath’s team has published many papers about Parkinson’s, but here is one detailing the experiment with Joy: Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum.

One of the really compelling parts of the podcast was about Joy having to choose whether or not to “use” her superpower. If she was buying groceries (pre-quarantine) and thought she smelled Parkinson’s on the clerk, is she responsible to say something? The podcast also referenced other existential questions. If you were to know that you would have Parkinson’s disease in the future, how should you live your life in the present? Would you even want to know?

One answer came from an Alzheimer's patient, who simply said "do the next right thing." It has become my quarantine mantra.

Citations:

Spiegel, A. (Producer). (2020, March 23). An Unlikely Superpower [Audio podcast]. Retrieved from https://www.npr.org/2020/03/23/820009335/invisibilia-an-unlikely-superpower

Trivedi, D., K., Sinclair, E., Xu, Y., Sarkar, D., Walton-Doyle, C., Liscio, C., Banks, P., Milne, J., Silverdale, M., Kunath, T., Goodacre, R., and Barran, P. (2019). ACS Central Science 5(4), 599-606
DOI: 10.1021/acscentsci.8b00879 

The Real Science Behind Pixar's "Inside Out"

Inside out is one of my all-time favorite animated movies. I moved to San Francisco at around the same age as the main character Riley moved to SF, and it totally captured the things that were going on inside my head during the move. Ever since, I've wanted to know how it was so relatable, and how much of the movie was based on actual data, so that's what I looked into this week.



I'll start with the setting. A large part of the movie takes place in "Headquarters", which looks and functions like the hippocampus, which is the part of the brain (and limbic system) responsible for memory. Memory comes in two time scales: short-term memory and long-term memory. Short-term memory keeps a limited amount of information easily accessible in your mind for a short amount of time to help learn or carry out a task. Having to remember the date and time of an appointment until you can find a paper or your phone to write it down on would be an example of short-term memory because you rarely need to hold on to this information for longer than a minute. Long term memory consists of everything that is not actively being used but still potentially necessary for understanding, learning, and functioning as a whole. If you don't have an immediate need for the recall of a particular piece of information, it is "stored" in long term memory. For example, I know how to make a chocolate cake but I don't need that information while I am doing chemistry, so it is stored until I am making the cake, when the information is actually needed. There is another kind of memory that is somewhere in between short and long term memory, called "working memory". It is thought to operate on the same time scale as short-term memory, but instead focuses on planning and carrying out behaviors and relies heavily on one's ability to control their attention. We do this whenever we read, so if you are reading this your working memory is activated! In order to understand what we are reading, we must process the whole sentence or paragraph and hold that knowledge to provide context for what we read next. In addition to the two time scales of memory, there are also two main memory systems: implicit and explicit memory. Implicit memory includes all things unconscious; emotional and skeletal responses, learning habits, and reflexive responses to stimuli. Explicit memory focuses on facts and events, like memories of your first day of school or random knowledge from AP US History that you can't seem to get rid of. Both of these memory systems are shaped by emotion and can be connected by emotion.
This brings us to the characters! Pixar represents the human spectrum of emotion and the influences of the amygdala as five Emotion characters; Joy, Sadness, Anger, Fear, and Disgust. In reality, there are six or eight principle emotions (depending on who you ask), but the only major one that seems to have been left out is Surprise.  In the movie, we see how the Emotions "color" Riley's memories. When a memory comes into the aptly named Headquarters, one of the Emotions presses a button and essentially decides what kind of memory it is. The pressing of this button represents neurons in the amygdala sending signals to the hippocampus, a process that affects what implicit emotions we associate with certain explicit memories. Most of the memories we see in Inside Out are only one color which is not accurate. As we all know, memories can be linked to many different emotions at once. The main premise of Inside Out is linked to the crossover between implicit emotion and explicit memory, and how much each of our emotions matters when it comes to forming new memories and recalling old ones.

After reading all of this about memory, emotion, and Inside Out, I'm more impressed than ever by the accuracy of this movie and I want to watch it again.

References:
Cowan N. (2008). What are the differences between long-term, short-term, and working memory?. Progress in brain research, 169, 323–338. https://doi.org/10.1016/S0079-6123(07)00020-9
Chamary, JV. (2015). How 'Inside Out' Explains the Science of Memory. Forbes. https://www.forbes.com/sites/jvchamary/2015/08/30/inside-out-science/#7a20e04b5184

Rigor Mortis Changes on Cause of Death

     The study of rigor mortis is a common forensic science to estimate time of death. When I looked at UCSB library's database for rigor mortis research, I found one author whose name popped up a ton on a series of older papers from the 1980s.
     The main paper I read involved looking at how rigor mortis varies across causes of death. Krompecher et. Al. analyzed rigor mortis between cases of nitrogen asphyxia, drowning, strangulation, and strychnine intoxications (i.e. carbon monoxide).
     Prior to this paper, scientists believed that certain factors can surely interact and influence rigor mortis, but they weren't sure how strong interactions were and between which variables they were present.
     To test varieties of rigor mortis, researchers experimented on 80 albino male rats and divided into groups. They were killed at the same time, and based on groups, were killed in different ways. After death, the rats are placed into a special apparatus for measuring. This apparatus is shown in the paper, and honestly looks pretty weird to me... I am not too sure overall about the ethics of this experiment, or whether it would be approved today (I would guess not).

     Figures 2 and 3 show graphs tracking rigor mortis across rats, and there is definitely a clear difference across variables based on the graph alone. All causes of death, however, also look like they follow a very similar track, so there is some uncertainty when I look at the graph as to whether the differences are significant enough.
     Overall, Krompecher et. Al. found that strychnine intoxication hastens rigor mortis onset, CO intoxication delays rigor mortis, and intensity of rigor may vary depending on cause of death.

Citation:
Krompecher, T., Bergerioux, C., Brandt-Casadevall, C., Gujer, H.-R. (1982) Experimental evaluation of rigor mortis. VI. Effect of various causes of death on the evolution of rigor mortis. Forensic Science International, 22(1),1-9.

Sleeping Adaptations

No one is sure what the function of sleep is, but it does seem to be essential for many animals. I read Sleep viewed as a state of adaptive inactivity,  where Jerome Siegel proposes that sleep may serve the purpose of conserving energy and regulating timing, thus increasing efficiency.

A great example of this is hibernation; it's an adaptation of decreased inactivity so that animals that can't migrate can survive the cold winter months. I read about hibernation here. True hibernation is a state close to death, where the animal's body temperatures may be close to freezing and their heart beats much much slower. They also take a long time to wake up. I'm not sure if true hibernation really is sleep. Bears are actually not true hibernators because they don't have such reduced temperatures, and they can wake up more quickly. Some true hibernators include some types of rodents, bats and hedgehogs. Here is a video of a bear and her cubs getting ready for hibernation.

Siegal goes on to discuss a study that found that carnivores tend sleep more than omnivores, and omnivores tend to sleep more than herbivores, which makes a lot of sense since herbivores have to avoid getting eaten. For example lions sleep for long hours and deeply, whereas giraffes sleep for very short durations and not very deeply. That reminded me of something I heard where horses don't  sleep lying down. That is not true, they do sleep while lying down, but they can also sleep standing up, allowing them to be ready to run if they need to. This lady explains the sleeping habits of horses well:

What about marine mammal sleep?
Walruses can go without sleep for days. They may not be as influenced by circadian variables because they are adapted to ocean tidal and weather features. Here is a walrus sleeping, although it looks pretty awake right there.

Cetaceans (whales and dolphins) don't really sleep in the same way that land mammals do at all. They have unihemispheric slow waves (USW) which is slowed activity in one hemisphere in the brain, and can occur for up to two hours. Sometimes they float at the surface, but a lot of times they keep swimming while they do this. Smaller cetaceans may never rest like this. It may be because they have to keep moving to keep warm since they have a greater relative surface area. Even though one hemisphere has reduced activity when they "sleep," cetaceans don't show reduced body activity on one side.  Thinking about Siegel's idea that sleep is used to conserve energy when it's not needed, it seems like cetaceans really need to use energy all the time and keep moving. The reason for the USWs might then provide a different reason for sleep. Here's a humpback whale "sleeping"

Earred seals show a mix between land mammals and cetaceans. While sleeping on land, they sleep like land mammals, but while sleeping in water they do have USWs, although unlike the cetaceans they do show reduced activity on one side of the body. Here is a hilarious video of some seals sleeping, although I don't think these guys are considered earred seals:

I hope you enjoyed learning about various animal sleeping adaptations. Here is one last video of a bunch of different animals sleeping. Alright, I think it's time for me to get some sleep.

Article Citation:
Siegel, J. M. (2009). Sleep viewed as a state of adaptive inactivity. Nature Reviews Neuroscience, 10(10), 747–753. https://doi.org/10.1038/nrn2697

Are Hiccups a Reflex Arc?

Related to reflex arcs, I wanted to explore what happens to your body and brain when you get hiccups, and whether that’s a reflex arc as well. Hiccuping is involuntary and occurs when an involuntary reflex causes your diaphragm to spasm. The diaphragm works to help your lungs fill and push out air to breathe. When it contracts, the lung volume becomes bigger, decreasing the pressure inside and allowing air to flow in because of the pressure gradient. When it relaxes, the volume decreases and pressure increases, forcing air out of the lungs. If the diaphragm spasms, air rapidly flows into the lungs and rapidly forces the vocal cords shut, causing the classic “hiccup” sound. Diaphragm spasms can be caused by multiple things such as a blow to the chest, cramps or flutters, or irritation of the phrenic nerve, which controls the diaphragm. Hiccups occur commonly in fetuses, children, and adults, and are not an issue if short-term. This paper includes a compiled list of remedies to cure short hiccup spells like respiratories maneuvers (holding your breath), nasal and pharyngeal stimulation (drinking/gargling water), and other remedies like pinching/acupuncture. However, if they last more than 48 hours and cause serious distress, they are of concern and can be indicative of an underlying condition. Chronic hiccups are potentially untreatable, but can be managed through therapeutic, medicinal, and behavioral treatments.

Hiccup in adults: an overview

S Launois, JL Bizec, WA Whitelaw, J Cabane, JP Derenne

European Respiratory Journal Apr 1993, 6 (4) 563-575;

Brains rock: Alex Honnold, fear, and the awesome amygdala!

Honnold on Half Dome

A professional “dirt-bag” rock climber, Alex Honnold is well known for his free solo (i.e. climbing without ropes or protection) ascents of some of the worlds biggest walls. In 2017, Honnold became the first person to free solo the 3,000-foot Freerider route on El Capitan in Yosemite, pushing him into the media spotlight as a symbol of fearlessness. A cognitive neuroscientist, Jane Joseph, was eager to see how Honnold’s brain allowed him to put himself in these high risk situations without fear taking over. 

The brains of high sensation seekers have been the focus of many neurological studies. People who are drawn to, and take risks for, intense experiences can find themselves chasing dopamine stimulants. While this can sometimes result in drug and alcohol addictions, for Honnold, free soloing ramps up his dopamine circuitry. Honnold’s dangerous climbs could become even more deadly if impulsivity overrides his normal conscientious and calculated approach. Joseph describes Honnold as a super sensation seeker who “pursues experiences at the outer limits of danger, yet is able to tightly regulate the mind and body’s responses to them.” 
After using a functional magnetic resonance imaging (fMRI) brain scanner, Joseph was able to dive deeper into the nature of Honnold’s “fearlessness.” When she received the fMRI scans of Honnold’s brain, Joseph focussed on the amygdala, commonly referred to as the brain’s fear center. A part of the limbic system, the amygdala is a cluster of neurons which plays a role in detecting threats and processing emotions such as fear. Unlike individuals who do not feel fear because they have a degraded amygdala (e.g. Urbach-Wiethe disease), it was apparent that Honnold’s amygdala was not damaged. However, in comparison to a control patient, another high-sensation-seeking male rock climber, Honnold’s amygdala was non-reactive to the stimuli provided. Asleep in his brain “like an old dog in an Irish pub,” his amygdala showed no activity (Fig.1). 
But why is Honnold’s amygdala less reactive, buffering him from fear induction? The answer to this is more complex. One possibility is that his prefrontal cortex is powerful enough to inhibit the amygdala’s response to threatening situations. Research has shown that humans can strengthen the prefrontal cortex’s ability to calm the amygdala by undergoing reconsolidation, or turning fearful memories into fearless ones. This is something that Honnold consistently does by keeping a climbing journal and picturing his moves. Similarly, he practices visualization before his climbs, imagining the worst outcomes, and strengthening his prefrontal cortex even more.
I recommend checking out the article “The Strange Brain of the World’s Greatest Solo Climber” that I linked below if you want to learn more!

Crosshairs mark the amygdala

Sources:
Feinstein, Justin S., et al. “The Human Amygdala and the Induction and Experience of Fear.” Current Biology, vol. 21, no. 1, 2011, pp. 34–38., doi:10.1016/j.cub.2010.11.042.

MacKinnon, J.B. “The Strange Brain of the World's Greatest Solo Climber.” Nautilus, 11 Aug. 2016, nautil.us/issue/39/sport/the-strange-brain-of-the-worlds-greatest-solo-climber.

Phone Bad... for your mental health?

     Hi, everyone! This week I found a paper that examines the relationship between smartphone use, sleep quality, depression, and anxiety in college students. I do think that lots of people tend to criticize young people for their cell phone use, blaming it on things that are in general unrelated.  However, since I've been at home and in quarantine, I have definitely noticed that my phone use has increased a lot, and my sleep quality has gone down. Lots of my friends are feeling the same way, so I decided to check out this study.
      In the study, college students in 3 groups were tested for anxiety, depression, sleep quality, and smartphone addiction. The three groups were no cell phone use, low cell phone use, and high cell phone use. It was found that depression and anxiety were higher in the high cell phone use group than the low cell phone use group. Depression and anxiety cause poor sleep, and poor sleep causes depression and anxiety. It is thought that any low sleep quality in the high use group is a result of this relationship, rather than a direct correlation between sleep quality and phone use. Other papers have found that cell phone use can hinder sleep, because of blue light or notifications interrupting sleep.
     It was also found that women, people with higher anxiety and depression, and younger people are more prone to smartphone addiction and overuse. So, it seems that the relationship is slightly more complicated than "phones make you depressed." There is a cycle where poor mental health leads to more cell phone use, which leads to poorer mental health, etc. I think this distinction is important, because devices like smartphones can be a very positive force, especially in a time like now. These devices allow us to stay connected in some way when we can't be together. I know I would be a lot sadder if I couldn't keep in touch with my friends using my phone.Check out this study for yourself if you're interested!

Citation: Demirci, Kadir, Akgonul, Mehmet, Akpinar, Abdullah. 2015. Relationship of smartphone use severity with sleep quality, depression, and anxiety in university students. Journal of Behavioral Addictions 4(2): 85-92.

Nervous and Endocrine System Involvement in Circulation

Hey Everyone!

I was really intrigued by how separate systems of the body are able to interact with others to respond to a variety of environmental pressures we face on a day to day pressure. I just wanted to give a very brief overview about some of the topics in the article I chose and share it with everyone.

The autonomic nervous system (ANS) regulates heart rate, blood pressure, heart contractions, and sweating. All of this is done to maintain homeostasis within our body. As the name suggests, the autonomic nervous system works unconsciously and is done by our spinal cord, brain stem, and hypothalamus. The ANS is made up if two subsystems: the sympathetic and parasympathetic systems. The sympathetic system works on the bodies fight or flight response and energy expenditure. The parasympathetic system works to keep our body in a restful state after a stressful event. The sympathetic system is activated during exercise, excitement, and heart failure. On the other hand, the parasympathetic system is activated during rest, sleep, or tranquility.

The cardiovascular system is also influenced by many endocrine hormones. For example, the adrenal glands release the hormones epinephrine and norepinephrine, which can activate or deactivate the sympathetic system. Epinephrine serves to increase the oxygen and glucose intake to the brain and skeletal muscle to initiate out flight or fight response. Inside the kidney, renin, calcitrol, can and thrombopoietin are produced and are all involved in the maintenance of the cardiovascular system. Renin is involved in the regulation of blood pressure and cardiovascular reflexes. Calcitrol works to increase the absorption of calcium and phosphate in our bodies. An abnormal amount of calcium can lead to plaque buildup and vascular stiffness. Thrombopoietin stimulates the production of megakaryocytes  in the bone marrow. This leads to the formation of platelets in out blood. As you can see, the cardiovascular system is aided by other systems in our body to maintain general health as well as a response to environmental stresses. The paper goes into much more detail than what was found here. Link below:


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404375/

Gordan, R., Gwathmey, J. K., & Xie, L. H. (2015). Autonomic and endocrine control of cardiovascular function. World journal of cardiology, 7(4), 204–214. https://doi.org/10.4330/wjc.v7.i4.204

Dividing and Conquering Apoptosis

After learning about the immune system this week, one of the topics I wanted to look into a bit more was apoptosis. During my high school biology class, I learned that apoptosis was programmed cell death, but I didn't understand the way the process worked, and how it could be detrimental instead of beneficial if done incorrectly.

There are two main ways for a cell to die (in a multicellular organism). Option A is necrosis, in which the cell is killed by something harmful or toxic. Option B is programmed cell death, such as apoptosis. There are a few other forms of programmed cell death besides apoptosis, but apoptosis is the best understood. Autophagy fits into the realm of option B.

Necrosis is a messier process than apoptosis. It involves the cell breaking open and spilling its contents to the outer tissue. This can cause inflammation. In contrast, apoptosis is much neater. The cell shrinks and its contents get divided into blebs, which are small chunks of the cell packaged into a membrane. Some organelles are broken into pieces and put into different blebs, and the DNA of the cell is cut up before being put into a bleb. The blebs signal for macrophages to come eat them.

Apoptosis is important for the immune system (think viral infections and removing cells that are no longer welcome) but it is also an important part of development. The human hand is a paddle while an embryo, and apoptosis helps carve apart the fingers. Without apoptosis in development, human hands would effectively be webbed.

Citation:
Delhalle, S., Duvoix, A., Schnekenburger, M., Morceau, F., Dicato, M. and Diederich, M. (2003). An Introduction to the Molecular Mechanisms of Apoptosis. Annals of the New York Academy of Sciences, 1010(1): 1-8. doi:10.1196/annals.1299.001

Liquid Ventilation: Breathing Liquids

At some point, we've all marveled at the superhero power to breathe underwater. Apparently, breathing while in a liquid is feasible.

In its most basic way of operation, our lungs pull in oxygen and push carbon dioxide out. Gills work the same way in fish, so long as the dissolved oxygen concentration is high enough. If a liquid is not very dense, and has enough space between its molecules for gaseous oxygen to dissolve, then the oxygen can be dissolved in high enough concentrations for mammals to breathe.

Scientists have identified some compounds such as perfluorocarbon that have this property. As I looked into liquid breathing, I also found that there were medical applications to help people get oxygen to more damaged and potentially blocked areas of the lungs by using the liquid media to get into places that were blocked and facilitate oxygen absorption.  As the patient slowly recovers, the concentration of the perfluorocarbon can be reduced to allow the person to resume breathing air.

Given the current pandemic and its affect on our lungs, I was trying to find if liquid breathing was being used in hospitals currently. The most I could find was a discussion on Reddit, which I have attached below. 

https://www.sciencedirect.com/topics/medicine-and-dentistry/liquid-breathing

https://www.reddit.com/r/AskScienceDiscussion/comments/fjavk5/can_liquid_breathing_be_a_cure_for_covid19/

Communication Between the Immune System and the CNS

So, I think that the nervous system is absolutely fascinating. Apparently, this coming week's topic is the nervous system, so here's a little taster into its leadership role within the body, as it pertains to the immune system.

First, a bit of science history: the field of neuroscience, as we envision it today in all its interdisciplinary glory, is relatively young. For quite some time, neuroscientists and other biologists had assumed that the blood-brain barrier (BBB) deemed it impossible for the central nervous system (CNS: also known as your brain and your spinal cord) to collaborate with other large bodily systems, such as the immune system. This might make some sense at first, because the extremely selective permeability of the BBB prevents the vast majority of pathogens and other harmful microorganisms from even entering the brain in the first place -- why would it need to "talk" with the immune system, then? If we think about this for just a few seconds more, we realize that lack of communication between the CNS and the immune system would be quite detrimental, if not deadly, for the body as a whole. The immune system cells absolutely need some method of communication between them, something intelligent, effective, and extremely quick, in order to integrate signals and assess risk -- neurotransmission, perhaps?

In fact, the interwoven nature of the CNS and the immune system are essential for our functioning in daily life, and their network does have a universal method of communication. As John touched upon in his lectures, and as Ioana Marin and Jonathan Kipnis describe in their concise review of communication between the CNS and the immune system (cited below), there exist CNS cells that communicate through production of immune particles (recall, cytokines and chemokines), as well as immune system cells that can communicate through neurotransmitter output and reception. The cells in our CNS that are able to communicate through immune components are called microglia. Glial cells are not classified as neurons, but rather exist for a whole plethora of reasons (depending on their specific structure), including structural support for neurons, facilitation of neurotransmission by protecting synaptic clefts, and removal of waste from the CNS. Though microglia are considered a type of "immune cell," their removal of waste and synaptic pruning (imagine a of trimming synapses that are weaker in order to strengthen existing ones to rearrange/fortify dendritic connections) are vital for efficient cognitive functioning. Marin & Kipnis point out that the microglia responsible for pruning within the hippocampal region require activation from a specific chemokine, CX3CL1, in order to provide this service to the brain within mice. Synaptic pruning has even been defined as a kind of homeostatic procedure. So, is the immune system crucial for your memory, as well as maintaining your health? This is one of the many questions being raised by the finding that the immune system and the CNS work together, speaking the same language of neurotransmitters, in order to keep you functioningI could probably go on for quite some time, so I'll end this here and likely come back with more nervous system facts in the coming weeks! 

Some microglia, up close: 

Citation:

Marin, I., & Kipnis, J. (2013). Learning and memory… and the immune system. Learning & memory, 20(10), 601-606. 

Eosinophilia

This week was probably one of my favorites because I’ve been waiting to learn more about our immune system. My excitement made it difficult to choose one topic to pursue in detail. I decided to learn more about the types of white blood cells, specifically eosinophils since they kill antibody-coated parasites. Seeing that I barely knew what these were, I went for an older paper that discussed the basics of eosinophils. The paper focused on eosinophilia, or an accumulation of eosinophils as a result of disorders such as cancer, allergic diseases, and parasitic (mainly helminth) infections. 

This accumulation can be beneficial or harmful. On one hand, eosinophilia can cause inflammatory effects that damage the body. However, they can also work against parasites. Eosinophils levels are usually tightly regulated; an abnormal level of eosinophils is an indication of an infection or disorder in the body. Eosinophilia can be an indicator for atopic causes, parasite infections, cancer, drug ingestion, or specific diseases like Well’s syndrome and Shulman’s syndrome. 

Interestingly, scientists can use eosinophil levels to determine the illness a patient is facing.  For example, moderate-to-severe eosinophilia is a response to infection by helminthic parasites. Distinct levels of eosinophilia can provide insight into the pathogenesis of disorders associated with eosinophils, as well as which drugs to treat these disorders. Lastly, I wanted to mention that eosinophilia occurs as a result of four processes, which are pictured in the figure below. If this image sparks your interest, I encourage you to check out the paper to get more into the science-y part of the paper! 

Citation: Rothenberg, M. E. (1998). EOSINOPHILIA. The New England Journal of Medicine, 338, 1592–1600. doi: 10.1056/NEJM199805283382206

Some Very Resilient Sponges!

     Hey, y'all! Hope everyone is doing well. I was really interested in sponge respiration after Claudia talked about how they exchange gas by direct contact with their environment, rather than through a respiratory system. I found an interesting paper on the effects of high sediment concentrations in the water on sponge respiration. Generally, sediment is thought to negatively affect sponges by accumulating inside them and reducing or stopping water pumping, which is critical for both feeding and respiration. The strange thing to me was that studies on this have produced contradictory results. Some sponges increase respiration rates as a response to sediment, and some decrease it. It is thought that an increase in respiration is an effort by the sponge to produce mucus to help the sponge tolerate the sediment. A decrease in respiration is likely an effort to prevent sediment from entering the sponge in the first place.
     In this study, a slight negative relationship between respiration rate and sediment concentration was found. This relationship was strongest at the end of a two-week recovery period, which I found interesting. It seems like the sediment does not bother sponges very much. Overall, though, this study did not find any very significant effects of sediment on sponge respiration. This is very surprising, and does nothing to give clarity to the several contradicting findings on this issue. Basically, after this study, there are really only more questions. Seeing as this study was published in March 2020, there is still much research to be done on this topic. To me, it is simply fascinating that we don't have a solid answer to such a simple question, regarding such a simple organism. I'll be looking out for more studies on this topic!

Citation: Cummings,  Vonda J., Beaumont,  Jennifer, Mobiilia, Valeria, Bell, James J., Tracey, Dianne, Clark, Malcom R., Barr, Neill. 2020. Responses of a common New Zealand coastal sponge to elevated suspended sediments: Indications of resilience. Marine Environmental Research.  155:104886.

Breaking the Blood Bank: An Alternative For Horseshoe Crab Blood

The blood of horseshoe crabs has been used in the production and testing of many types of medicine due to its awesome ability to serve as a pathogen detector and quality control tool. However, although horseshoe crabs are kept alive after the blood-drawing process and are not going extinct, their numbers seem to still be dropping (1). Because of this, scientists are trying to find alternatives to using the blood of horseshoe crabs in biomedical sciences. According to (2018 Maloney et al), a few alternatives to the pathogen detecting test, the LAL (Limulus Amebocyte Lysate) test, were tested and the effects were observed and recorded. The first alternative tested came from cloned proteins of the main binding agent, rFC, meaning that it could be manufactured without the need to bleed the horseshoecrabs and hopefully with a similar potency(1). However, sadly the synthetic alternative was not as efficient as the "real-deal", leading this practice to never out compete the old strategies. After this, the researchers in this paper ran more tests to fully analyze the efficacy of this alternative in hopes that it would help makes the synthetic test commonplace. It was found that the LAL test from the horseshoe crab is a general test without specific targets that often yield false positives. The rFC test, on the other hand, is specific to endotoxins and thus not likely to have false positives(1). Not only this, the rFC test has higher and more reliable detection rates than the LAL test as is a cheaper process. Because of this discovery, and also how recent it was, it would not be surprising if the rFC test made it so that horseshoe crab blood was no longer necessary, accounting for a 90% reduction in LAL usage, for lab testing in the future(1).

1.)Maloney T, Phelan R, Simmons N (2018) Saving the horseshoe crab: A synthetic alternative to horseshoe crab blood for endotoxin detection. PLoS Biol 16(10): e2006607. https://doi.org/10.1371/journal.pbio.2006607

How an Insect Egg Breathes

Sphinx Moth, Manduca sexta
pc: Carol Wolf, via BugGuide

After learning a bit about insect respiration this week, I wanted to learn more about respiration at all stages of an insect’s life cycle. One interesting article analyzed the egg stage in the life cycle of the sphinx moth, and their trade-off between holding onto their water, and getting oxygen from their environment. The eggs are deposited with all of the water they will have access to until they feed as a juvenile insect. For this species, they will only lose water during their egg stage, so they have incentive to conserve it.


Since they are small, these eggs are almost always isothermal with their environments, and therefore experience changes in temperature-driven metabolic rates. This causes fluctuations in their need for oxygen. As stated in the article, “it appears that eggshells are designed so that embryos give up some metabolic potential in order to conserve substantial quantities of water.” There is a tradeoff for the insect: a shell that is very efficient at keeping water may be very inefficient at taking in oxygen. This paper analyzed the layers of the eggshell, and proposed potential layers that allow for oxygen transport but not water transport.


Another interesting point was that in the late egg stage of this insect’s life cycle, its metabolic rate is too high for the oxygen allowed via diffusion in the liquid-filled embryonic tracheal system alone. At this point, the embryonic tracheal system suddenly fills with air. This step reminded me of the human baby’s first intake of breath described in lecture.

Source:

Woods, H., A. (2010). Water loss and gas exchange by eggs of Manduca sexta: Trading off costs and benefits. Journal of Insect Physiology 56(5), 480-487. 

https://doi.org/10.1016/j.jinsphys.2009.05.020

Clinical Immunology Study on COVID-19 Patients

Hi all,
From John's lectures on immunology, I decided to try and look at some of the extremely recent immunology studies done on the COVID-19 pandemic.  I found a study from the Clinical Immunology  journal that looked at the use of anti-inflammatory medication on COVID-19 patients.

As clinical immunologists, Zhang et al. tried several rounds of inflammation management of critical COVID patients in Wu Han. The scientists utilized tools such as teleconsultations and conferences to discuss the use of anti-inflammatory drugs on these severe patients.  Severe symptoms of COVID were listed in the paper, and as long as a patient experienced these critical features, immunologists found that there was often an inflammatory cytokine storm in these patients. Typically, cytokine storms show up in patients with rheumatic diseases, tumor immunotherapy, and other kinds of infectious diseases because they imply organ failure and inflammation. In regard to coronavirus, it seems as though the cytokine storms mainly damaged lungs and resulted in some fetal complications. Following the proportion of COVID patients that were labeled as severe, a smaller level that transitioned into the most severe state experienced hyperinflammation, cases in which anti-inflammation therapy (as researched by Zhang et al. in this study) becomes essential.

Another aspect of COVID-19 looked at by this paper was the impairment of the immune system in patients via lymphocytopenia. In severe patients, as we learned in John's lectures, memory helper T cells and regulatory T cells were at extremely low levels. Primarily, lesser T cells were found in the lymph nodes and the spleen. The clinical immunologist authors of this paper stress how antiviral and anti-inflammatory drugs are super important in this pandemic as the numbers of severe cases continues to increase; as more and more people are placed under critical condition, these therapies may be some of the main helpers.

One of the treatments this paper explores is chloroquine and hydroxychloroquine, as these drugs are commonly used as anti-virals; however, further investigation still needs to occur in order to say for certain whether or not they can help in COVID patients. As of now, there have been 15 clinical trials, and I look forward to seeing where these trials take COVID-19 research!


Citation:
Zhang, W., Zhao, Y., Zhang, F., Wang, Q., Li, T., et. al. (2020) The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clinical Immunology, 214. DOI: 10.1016/j.clim.2020.108393

The Relationship Between Breathing and Anxiety

In times of stress and/or anxiety, one of the main things we hear is "take a deep breath". I've used this strategy more times than I can count, but I realized I had no idea why a deep breath helps on a biological level.

One of the ways that relaxed breathing can come into play in stressful situations is by controlling the "fight or flight" stress response. This kind of stress and anxiety is an evolutionary adaptation that prepares our bodies for life-threatening situations. It can manifest in blurred vision, heart palpitations, sweating, dizziness, and nausea among other symptoms. This response is useful in survival situations where the two logical options are to either stay and fight or run away because it focuses the body's energy and oxygen towards the muscles. This is not a helpful response for most of the stressful or anxiety-inducing situations we may find ourselves in on a daily basis; things like taking a test or worrying about the future of the world after coronavirus. Nevertheless, stress releases adrenaline into the bloodstream leading us to hyperventilate which supplies more oxygen to the muscles, but over time leads to an imbalance in the levels of oxygen and carbon dioxide in our blood. This imbalance causes dizziness, faintness, palpitations, and chest pain, all of which make everyday tasks pretty difficult. This is where the deep breaths come in. Breathing in a slower and more relaxed fashion rebalances the oxygen and carbon dioxide levels in our blood, which signals to the central nervous system and to the brain that the situation does not warrant a "fight or flight" response, and the symptoms will begin to ease.
These responses to stress are consistent with more severe forms of stress and/or anxiety like anxiety and panic disorders. The path between anxiety and breathing appears to be a two-way street. Intense anxiety can be the cause of hyperventilation or vice versa. Multiple anxiety disorders have been linked to altered breathing and perception of altered breathing, so naturally, this is a field of great interest in both psychology and psychiatry.  This is especially true for panic disorder (PD), which is characterized by unexpected panic attacks that generally start with a sudden rise in terror and cardiorespiratory symptoms. Some research suggests that part of the heritability of PD is the heritability of CO2 sensitivity, which can result in a hyperactive homeostatic response that essentially tells the body "you are suffocating, you aren't getting enough air", which is one of the causes of panic attacks. Panic attacks are not life-threatening but often feel as though they are, because your body has managed to thoroughly convince you through a myriad of hormones and cardiorespiratory symptoms that you cannot breathe and that the panic will never end. Deep, relaxed breathing can help with this as well. Cognitive Behavioral Therapy (CBT) often uses mindfulness and breathing techniques to preemptively ward off panic attacks or to lessen anxiety when it has the potential to reach a panic attack. Because panic and anxiety disorders are recurring and often life-long conditions, CBT helps establish breathing strategies that can help someone out of extreme anxiety or near panic when a deep breath doesn't cut it. Even in the most extreme anxiety scenarios, controlled breath is shown to be a critical tool for managing cardiorespiratory symptoms and getting the body back to normal.

Paulus M. P. (2013). The breathing conundrum-interoceptive sensitivity and anxiety. Depression and anxiety, 30(4), 315–320. https://doi.org/10.1002/da.22076

Sardinha, Aline, Freire, Rafael Christophe da Rocha, Zin, Walter Araújo, & Nardi, Antonio Egidio. (2009). Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications. Jornal Brasileiro de Pneumologia, 35(7), 698-708. https://doi.org/10.1590/S1806-37132009000700012

A PDF I also used as a reference: https://www.sfh-tr.nhs.uk/media/3782/fight_or_flight_and_relaxed_breathing.pdf

Art and Nature

I thought the art section of the Natural History field trip was super interesting, so this week I did some investigation into art in biology. I love making art myself, and my main source of inspiration is nature, so I'm always inclined to learn more about the two, and especially together. 

I looked more into Kunstformen der Natur (Art forms in Nature) by Ernst Haeckel, who was a German zoologist and evolutionist. He made the Genealogical tree of life we looked at last quarter. (Not accurate) Learn more about him here. Kunstformen der Natur is full of lithographic plates of organisms he drew. Each plate has a classification of organisms. You can look at the full text here. Here's a link to just the plates. I also looked more into lithography. It's a really intricate and complicated process of printmaking that takes advantage of hydrophobic and hydrophilic materials. It replaces whatever you drew on a stone block with an ink, and then you can print something that has the feel and detail of a drawing. Here's a really good Khan academy video about it. I think it was originally used to print music, but it almost seems like it would be faster to just write the music over and over again.

Here are some of the plates: (OOOooooooOooooooooo!)

I also looked at Werners Nomenclature of Colors, which developed a nomenclature for classifying and standardizing colors. Werner originally made it to classify the colors of minerals. Later, Patrick Syme developed the book further, adding color swatches and more colors to encompass living nature. The book has 110, colors, and Darwin used it on his voyage to describe species. Here is a link to the book.