Inhibiting Complement System to Aid in Genetic Engineering

While taking a deeper look into the complement (C) system, I came across this paper that focused on how the inhibition of the C system may play a role in improving the efficacy of viral genetic engineering vectors. Specifically for this paper, researchers had noticed that the use of baculovirus as a vector for gene transfer in liver cells worked in vitro but had drastically reduced gene transfer in the presence of human blood serum. They hypothesized that the baculovirus was triggering the C system components that remained in the serum which then caused this drop in efficacy.

By making use of a monoclonal antibody that inhibits a late-stage component of the C system, researchers were able to observe increased survival of baculovirus vectors in human serum. Researchers were also able to protect baculovirus vectors in serum and whole blood samples by using Cobra Venom Factor (CVF)  which mimics a component in the C cascade and results in depletion of the pathway, therefore inhibiting any cascade activation from the baculovirus.

While this paper focuses on increasing the efficacy of a single gene transfer vector, it can also be used to open up questions about the efficiency and biocompatibility of many other vectors as well.


Hofmann, C., Strauss, M. Baculovirus-mediated gene transfer in the presence of
human serum or blood facilitated by inhibition of the complement system.
Gene Ther 5, 531–536 (1998). https://doi.org/10.1038/sj.gt.3300607

At the Strike of Midnight

Parrotfish are vital characters in the coral reef ecosystem. As they munch on the macroalgae and sponges that, if left unchecked can smother reef-building corals, Parrotfish take on the role of gardeners pruning back growth and keeping it in a healthy range. The health and behavior of the near hundreds of different species of parrotfish found on the reef, can be used as a gauge for how the rest of the system may be fairing.

While helping a conservation group in the Dominican Republic, my group was learning how to ID the different species and life-cycles of parrotfish to record the populations most commonly found on the reef. Our instructor insisted that before we can learn to ID the parrotfish in the sea, we must ID the parrotfish within ourselves. Given my intensely blue hair at that time, I was likened to a midnight parrotfish, but (as you will see from this paper) I hope this was a comparison of only appearance and not temperament.

Midnight Parrotfish Scarus coelestinus

A very short paper from the Burkpile lab here at UCSB, studied the behavior of groups of juvenile Midnight parrotfish. While normally herbivorous, these juveniles will occasionally hunt in packs and raid the nests of other fish (mainly sergeant major damselfish) for eggs. While it is common for some species of fish to raid the nest of competing individuals of the same of a different species, this paper points out that this seems to be the first time that this behavior has been seen in parrotfish.

Adam, T.C., Kelley, M., Ruttenberg, B.I. et al. Groups of roving midnight parrotfish (Scarus coelestinus) prey on sergeant major damselfish (Abudefduf saxatilis) nests. Mar Biodiv 47, 11–12 (2017). https://doi.org/10.1007/s12526-016-0475-4

How Fight or Flight Actually Gets Triggered (its not the chemical you think):

I got interested in the other functions of bone. It turns out, in addition to being more "alive" than we think, bone provides a pathway for the secretion of certain hormones. Bone also plays an important part in the triggering of the acute stress response known as the fight or flight response. The hormone osteocalcin helps bring about this acute stress response. When the body is under acute stress, the brain signals the skeleton to release this osteocalcin.
The reason why bone specifcally triggers this response is pretty interesting. As the skeleton evolved to protect us, the researchers of the study I looked into hypothesize that the stimulation of flight or fight response makes perfect sense as yet another physiological mechanism that protects the organism.
 "If you think of bone as something that evolved to protect the organism from danger -- the skull protects the brain from trauma, the skeleton allows vertebrates to escape predators, and even the bones in the ear alert us to approaching danger -- the hormonal functions of osteocalcin begin to make sense" is how they phrase it.
In order to test weather osteocalcin was necessary or sufficient to the triggering of fight or flight, the researchers took mice that had been engineered to not produce osteocalcin and wild type mice and presented them with stressors. The mice that had been engineered, as it turns out, were completely indifferent to the stressors while the wild type mice were stressed as predicted. Additionally, the researchers were able to create a fight or flight stress response in the modified mice just by injecting a large amount of osteocalcin into the mice.
This study shows how animals that do not have adrenal glads and cannot produce adrenaline can have normal fight or flight responses. Adrenaline is not necessary for fight or flight.
In conclusion, adrenaline gets a lot of credit for the fight or fight response, when that credit should really go to the skeleton and the hormone osteocalcin.

How The Lamprey Eel's "Cough" May Have Evolved into Lungs:

The lamprey is, according to this study, the most basal (closest to the bottom of the phylogeny tree) vertebrate in terms of the evolution of the lung. One of the most critical elements of breathing is the neurological element of a "rhythm generator". This rhythm generator must be sensitive to metabolically produced CO2 and be able to rhythmically activate based on the levels of CO2 present/metabolic demand. This is what allows our bodies, and all bodies that breathe like we do, to breathe automatically.

While lamprey eels may not have lungs specifically, they do have what has been identified as the very first rhythm generator to evolve. In order to gather nutrients, lampreys bury themselves in the sediment of bodies of water and generate a rhythmic flow of water through their bodies. This water flow not only collects nutrients, but satisfies metabolic gas exchange requirements. This slow rhythm generation is also called the lamprey's "cough".

Additionally, the researchers isolated lamprey brain stems and found that they rhythmically stimulate the ventilatory muscles that allow for this rhythmic water flow.

So, anyway, we have these weird looking guys to thank for the fact that we breathe automatically.

Oceanic Iron Fertilization: A 2020 Update

The topic of oceanic iron fertilization to combat climate change was a hot topic in the early 2000s, and in 2012 one of the first large scale operations to employ this technique was completed by the Haida Salmon Restoration Corporation under the direction of businessman Russ George.

The idea is that if the ocean is seeded with an excess of iron, this iron will stimulate a growth of phytoplankton. The phytoplankton will then take in carbon dioxide and fix the chemical. When they decompose the excess carbon will not be released back into the atmosphere, the phytoplankton that fixed it will fall to the bottom of the ocean, taking the carbon out of circulation.

However, a recent study done at MIT concluded that, while iron fertilization may stimulate the growth of phytoplankton in a lab, phytoplankton in the wild already exist in a delicate balance with their available nutrients. Through a series of complicated mechanisms, adding iron would cause no change to the total amount of phytoplankton in our oceans. Additionally, it has been hypothesized that the fertilization would favor some species of plankton over other, leading to large toxic algal blooms, devastating other species. One of the lead researchers on the MIT project concluded that, “I think we should tackle the source of the problem — reducing our carbon emissions — rather than trying to come up with band-aids. " I agree with this sentiment, though, people are still looking into iron fertilization even now (https://www.biogeosciences.net/15/5847/2018/) . The idea isn't quite dead yet. 

https://news.mongabay.com/2020/03/climate-fix-fertilizing-oceans-with-iron-unlikely-to-sequester-more-carbon/

(algal bloom)

The Immune Response to Discrimination

Hi everyone, congratulations (!) for being in the home stretch of the most unprecedented quarter of our undergraduate careers. Here's the citation for the article I presented much too quickly about, proposing a physiological pathway linking perceived, chronic discrimination to a stress response, mediated by three biomarkers, that ultimately leads to poor relationship outcomes. Again, an interesting biological perspective with which to view the inherently unjust structure of American society.

Doyle, D. M., & Molix, L. (2014). Perceived discrimination as a stressor for close relationships: Identifying psychological and physiological pathways. Journal of behavioral medicine, 37(6), 1134-1144.

Tropical Rainforest in the Antarctic

Here's the citation for the article identifying a temporary rainforest near the south pole about 30 mya.

J Klages, U Slazmann, T Bickert, C Hillenbrand, K Gohl, G Kuhn, ... R Dziadez. 2020. Temperate rainforests near South Pole during peak Cretaceous warmth. Nature 580, 81-86. 10.1038/s41586-020-2148-5.

Are Ticks Venomous?

Hi everyone,

Here's the citation to the paper I discussed during today's presentation in case anyone is interested :)

Citation:

Cabezas-Cruz, A., & Valdés, J. J. (2014). Are ticks venomous animals?. Frontiers in zoology, 11, 47. https://doi.org/10.1186/1742-9994-11-47

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