Probiotics2

The Rise of Probiotics: The Impact of Gut Bacteria on the Immune System

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Introduction

Probiotics–defined as live microorganisms that offer health benefits–have gained significant attention for their potential to improve gut health and support the immune system. These beneficial bacteria are primarily found in fermented foods and supplements, playing a crucial role in maintaining balance within  the gut microbiota. In other words, they can impact the immune system’s function. The intricate relationship between the gut and the immune system is crucial, as around 70% of the body’s lymphocytes (a type of white blood cells crucial for the immune system) reside in the gastrointestinal tract. Although many studies show their beneficial effects on the human body, there is a lack of definitive evidence supporting the benefits of specific strains of bacteria or probiotic dosages. As a result, this article will discuss the effects of probiotics on the immune system, highlighting their role in reducing the risk of infections, allergies, and autoimmune conditions. 

Gut Microbiota

The gut microbiota is a system of trillions of microorganisms within the human gastrointestinal tract. This system contains bacteria, fungi, and viruses, with bacteria being particularly influential on health. The gut microbiota plays a crucial role in interacting with the innate and adaptive immune system, maintaining homeostasis and preventing inflammation. It helps with digestion, vitamin production, protection against harmful pathogens, and the creation of fatty acids that facilitate communication between the gut and immune cells. The gut epithelial cells form a mucosal barrier to separate the microbiota and the immune cells to prevent harmful substances from entering the bloodstream. If the interaction between gut bacteria and the immune system is disrupted, harmful bacteria called “Gram-negative bacteria” grow and damage the mucosal barrier, leading to infections and  increased intestinal permeability. 

Additionally, when the gut microbiota becomes imbalanced (gut dysbiosis) with increased harmful bacteria, it negatively impacts the immune system, causing inflammation, oxidative stress, and insulin resistance. Gut dysbiosis is caused by various factors, including the use of antibiotics and antimicrobial agents, drugs, smoking and alcohol, physical and psychological stress, chronic inflammation, and an unbalanced diet. Over time, chronic dysbiosis can lead to long-term conditions such as type 2 diabetes, cardiovascular diseases, inflammatory bowel diseases, autoimmune disorders, and certain cancers. Probiotics play a significant role in the gut microbiota composition, which can inhibit the growth of harmful bacteria in the gastrointestinal tract. As a result, it helps the host build a healthy intestinal mucosa protective layer, decrease permeability, and enhance the immune system. 

How probiotics interact with the immune system

Probiotics can strengthen the gut barrier, preventing harmful pathogens from entering. They interact with special immune cells in the gastrointestinal tract, such as dendritic cells, macrophages, and T and B lymphocytes. They also interact with the host’s intestinal cells at the surface of the intestinal barrier, including the intestinal epithelium and underlying lamina propria.

Figure 1

When consuming food with probiotics, they adhere to intestinal epithelial cells and send signals to the immune cells by Pattern Recognition Receptors (PRRs). Cytokines, which are stimulated by probiotic bacteria, activate T-regulatory (Treg) cells, maintaining immune homeostasis in the intestinal mucosa. Treg cells help suppress a strong immune response, which could lead to problems such as allergies (where there is a strong immune response to harmless substances causing allergic reactions). There are specialized enterocytes (specialized cells that line the inner surface of the small intestine and play a crucial role in nutrient absorption)  called “Microfold cells” (M cells), which act as messengers and transporters, passing information about harmful bacteria to immune cells and transferring intestinal antigens to dendritic cells. Depending on the situation, the intestinal Dendritic cells activate Th1, Th2, or Th17 immune responses. 

Th1 immune response is responsible for fighting intracellular pathogens such as viruses and bacteria, activating macrophages to kill infected cells. 

Th2 defends against extracellular parasites and handles allergies, activating B cells to produce antibodies (IgE) for defense. 

Th17  targets extracellular bacteria and fungi, activating neutrophils (the most abundant type of white blood cell in the innate immune system) to increase inflammation and fight infection.

Additionally, probiotics induce the maturation of B cells, to create IgA antibodies, which then produce plasma cells that stick to germs to present bacterial adhesion to the host’s tissues. 

Benefits of Probiotics on Immune and Human Health

Probiotics are mainly Gram-positive bacteria, including species belonging to the Lactobacillus and Bifidobacterium genre, such as Escherichia coli, Enterococcus, Pediococcus, and Yeast species. They have several beneficial effects, such as ameliorating innate immune responses and related anti-pathogenic/inflammatory activities, improving the absorption of beneficial nutrients, and decreasing food intolerance. 

They also inhibit the growth of pathogenic bacteria by synthesizing compounds with low molecular weight, such as acetic and lactic acids and “bacteriocins, ” which are antimicrobial compounds with large molecular weights. Bacteriocins produced by probiotics include lactacin B from L. acidophilus, Bifidocin B from Bifidobacterium bifidum NCFB, plantaricin from L. plantarum, and nisin from Lactococcus lactis. These compounds have shown inhibitory effects against Gram-negative pathogens, such as H.pylori. 

The gut barrier is essential for separating the gut bacteria and the body. Mucus is a secretory immunoglobulin A (sIgA), an antibody that plays a critical role in the immune system at the mucosal sites. The sIgA produces plasma cells in the intestinal tissues and transports antibodies across the intestinal epithelial cells into the gut lumen. The antibody binds to pathogens and toxins, preventing them from causing harm through immune exclusion, a non-inflammatory response. Probiotics have been shown to increase the number of sIgA-producing cells in the gut and other mucosal areas, such as the bronchus and mammary glands, exhibiting how probiotics can enhance the immune response by prompting the production of sIgA. 

Conclusion

Probiotics play a critical role in modulating the gut microbiota, positively impacting the immune system. Their interactions with various immune cells help maintain immune homeostasis, strengthen gut barriers, and enhance the body’s ability to fight against infections, allergies, and autoimmune disorders. Although the effectiveness of specific probiotic strains and optimal dosages are still being researched, current evidence demonstrates their ability to support innate and adaptive immunity. A deeper understanding of the gut-immune relationship can contribute to multi-faceted approaches involving probiotics, which have considerable promise in preventing immune disorders, potentially enabling more targeted therapeutic applications.

Sources:
Cleveland Clinic. (2024, April 16). What Is Gut Dysbiosis? Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/dysbiosis
Gourbeyre, P., Denery, S., & Bodinier, M. (2011). Probiotics, prebiotics, and synbiotics: impact on the gut immune system and allergic reactions. Journal of Leukocyte Biology, 89(5), 685–695. https://doi.org/10.1189/jlb.1109753
Liu, Y., Wang, J., & Wu, C. (2022). Modulation of Gut Microbiota and Immune System by Probiotics, Pre-biotics, and Post-biotics. Frontiers in Nutrition, 8. https://doi.org/10.3389/fnut.2021.634897
Maldonado Galdeano, C., Cazorla, S., Lemme Dumit, J., Vélez, E., & Perdigón, G. (2019). Beneficial Effects of Probiotic Consumption on the Immune System. Annals of Nutrition and Metabolism, 74(2), 115–124. https://doi.org/10.1159/000496426
Mazziotta, C., Tognon, M., Martini, F., Torreggiani, E., & Rotondo, J. C. (2023). Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health. Cells, 12(1), 184. https://doi.org/10.3390/cells12010184
Wang, X., Zhang, P., & Zhang, X. (2021). Probiotics Regulate Gut Microbiota: An Effective Method to Improve Immunity. Molecules, 26(19), 6076. https://doi.org/10.3390/molecules26196076
Yoo, J., Groer, M., Dutra, S., Sarkar, A., & McSkimming, D. (2020). Gut Microbiota and Immune System Interactions. Microorganisms, 8(10), 1587. https://doi.org/10.3390/microorganisms8101587 (Figure 1)

Photo from Kerry Johnson

Dragonflies: Nature’s True Apex Predators and Their Surprising Scientific Relevance

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Introduction

With extraordinary optics, lighting reflexes and remarkable flight control, dragonflies can rotate 360 degrees for up to five times in a single second. Though the flight of their prey is often an unpredictable zig-zag pattern, dragonflies’ midair hunting success rate remains at around 95%. Comparably, the success rate of wolves is ~20%, ~30% for cats, and ~50% for Great White Sharks.

Their flight is just one of the many factors scientists are interested in understanding, with the plan to integrate their biological adaptations into human engineering.

Photo by Kulsawad

Inspiringly Precise Flight

The flight of this incredible insect has been studied in controlled experiments, mimicking a predator-prey environment using tiny beads at various velocities. It was observed that dragonflies consistently flew just one meter quicker than the bead. These findings demonstrated the minimal effort needed for such precise flight, attesting to their remarkable instincts. They can enhance humanity’s ongoing technological development, used specifically in the interception of drones and other flying objects.

Unforeseen Mercury Pollution Tracker?

ercury is a toxin that damages brain development in both humans and animals, and much of it comes from human activity – like the usage of fossil fuels in power plants and medical waste disposal. It accumulates in water, becoming Methylmercury, and if exposed to high levels of it, concerns in human fetal development arise. Due to the fact that dragonflies can thrive in nearly every aquatic habitat— even ones in the desert— their larvae are useful for collecting data on ecosystems.

Photo by David M. Restivo

Mercury contamination was previously thought to be low in desert ecosystems. However, the nationwide Dragonfly Mercury Project, led by the United States Geological and National Park Services, recently discovered that there are surprisingly high levels of mercury in dragonfly larvae found in deserts.

Summary: Nervous System and Machine Integration

Once the dragonfly’s nerve cell functions and neuronal processing was adapted to machine learning, neuroscientists, computer scientists, and mechanical engineers collaborated in the creation of an algorithm that mimicked the insect’s visual tracking ability. It could then be used in autonomous pursuit robots, making them 20 times faster than previous algorithms, while staying just as accurate!

Dragonflies. They really are as impressive as their name.

References
Sherwin, F. Aerial Engineering and Physics of the Dragonfly. https://www.icr.org/article/13497
Communications and Publishing. Dragonflies Reveal Surprising INsights into Mercury Pollution.
https://www.usgs.gov/dragonfliesandmercury
New Hampshire Department of Environmental Services. Mercury: Sources, Transport, Deposition and Impacts. https://www.des.nh.gov/sites/g/files/ehbemt341/files/documents/2020-01/ard-28.pdf
US Environmental Protection Agency. Health Effects of Exposures to Mercury. https://www.epa.gov/mercury/health-effects-exposures-mercury
Forest and Rangeland Ecosystem Science Center. The Dragonfly Mercury Project. https://www.usgs.gov/centers/forest-and-rangeland-ecosystem-science-center/science/dragonfly-mercury-project
Division of Research and Innovation, University of Adelaide. Dragonfly technology provides pinpoint accuracy and super speed. https://www.adelaide.edu.au/research/news/list/2019/08/16/dragonfly-technology-provides-pinpoint-accuracy-and-super-speed

maglev2

High Speed and Low Emission: Maglev Trains

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In 1820, Hans Christian Ørsted conducted an experiment that redefined the worlds of both science and engineering. Upon passing a current through a wire suspended above a compass and observing the compass needle move, Ørsted was able to conclude that the electric and magnetic forces – both recognized as separate forces – were indeed related, and thus, unified. This observation was further expanded on  by James Maxwell, who later asserted that changing electric currents can produce electromagnetic fields, thus establishing the existence of electromagnets. Since then, electromagnets have become the keystone to technological advancements that have contributed to the development of MRI devices in medicine, electrical circuitry used in numerous electrical applications, and maglev trains in transportation. 

Since 1984, numerous countries worldwide have utilized maglev trains to transport people across large distances, the first of which being located in Great Britain. The most famous maglev train in the world, however, is the Shanghai Maglev, which connects the Pudong International Airport to various neighborhoods in Shanghai’s Pudong district. The train is able to reach record speeds of up to 501 km/h (301.3 mi/h) and was able to transport a record number of 53 million passengers in 2023.

While there are three primary types of maglev operating systems, most operate using a rudimentary  principle that is discussed in the majority of high school science classes: principles of magnetic attraction and repulsion, though on a much larger scale. For example, the most common mechanism used on maglev trains utilizes cars that have four magnets on the bottom corners. The magnets beneath the train car have opposing poles to the ones on the bottom of the track; when electricity runs through these magnets, the trains begin to levitate. Moving trains forward requires another set of electromagnets. Electromagnets on the sides of the tracks are placed so that their poles alternate with respect to the ones on the train car, (ie.alternating between north and south), and therefore, pulling it forward using attractive and repulsive magnetic fields.  While levitation helps the train gain speed, guide wheels are often used for stability, and ensure that the train remains on the tracks.

Figure 1, Source: (Whyte)

As the train accelerates, its levitation increases. Several trains can levitate up to 4 inches (10 mm) above train tracks at high speeds, which also serves to considerably reduce the amount of friction acting upon the train. This allows maglev trains to reach significantly higher speeds than their diesel or rail counterparts. While they still experience some friction from air resistance, there is less energy lost to heat and sound, which are common characteristics of traditional rail trains. Ultimately, as the majority of their energy is directed towards propelling the train forward and allowing them to reach higher speeds, maglev trains are praised for being an energy-efficient alternative to traditional trains.

Due to the fact that maglev trains employ the use of electricity, as opposed to fossil fuels as an energy source, they also produce fewer carbon emissions, making them a “greener” source of transportation that reduces traffic congestion in urban areas. According to Sayeed Mavani from the McGill Business Review, plans to develop a high-speed maglev rail system in the northeastern United States will connect various neighborhoods across northeastern states, while indirectly helping “reduce current rail energy consumption by 30 percent.” This project is also projected to increase the US Gross Domestic Product (GDP)  by approximately “$254 million annually,” demonstrating  that maglev trains have the potential to substantially boost the economy. While initial funding to build maglev systems from scratch may be expensive, the long term benefits offered are too great to ignore. As a highly efficient machine displaying a wide array of consistently positive benefits, maglev trains are a low energy, highly efficient method of transportation that should be implemented on a global scale to reduce carbon emissions. 

Works Cited

  • BYJU’S. “Uses of Electromagnet with Its Applications in the Practical World.” BYJUS, 2023, byjus.com/physics/uses-of-electromagnet/. Accessed 27 August 2024.
  • “China: Number of Passengers on the Beijing-Shanghai High Speed Rail Line 2023 | Statista.” Statista, Statista, 2023, www.statista.com/statistics/1074379/china-number-of-passengers-transported-on-beijing-shanghai-high-speed-rail-line/. Accessed 28 Aug. 2024.
  • Li, Shiyi. “State of the Art and Future Development of Magnetic Levitation Technology.” Highlights in Science, Engineering and Technology, vol. 31, School of Electrical and Electronic Engineering, North China Electric Power University, Baoding, China, 2023. Accessed 26 August 2024. 
  • Mavani, Sayeed. “Travelling Green: Is Maglev the Future of Eco-Friendly Transportation?” McGill Business Review, McGill Business Review, 23 August 2021, mcgillbusinessreview.com/articles/travelling-green-is-maglev-the-future-of-eco-friendly-transportation-1. Accessed 25 Aug. 2024.
  • Mitchell, Alanna. The Spinning Magnet. Penguin Random House, 2018. Accessed 22 August 2024.
  • Whyte, Chelsea. “How Maglev Works.” Energy.gov, US Department of Energy, 14 June 2016, www.energy.gov/articles/how-maglev-works. Accessed 27 August 2024.
molecular3

Molecular Discovery: Exploring the Implications of Digital Chemistry on Drug Development

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Introduction

Humans have identified, synthesized, and even tested millions of molecules thus far. However, out of the near-infinite possibilities, only a small fraction of molecules have been discovered thus far. But what if it was possible to exponentially accelerate this process?

Current System

Figure 1: leaders-mena.com

Generally, drug discovery is a long, arduous process; while thousands of molecular compounds and existing treatments are tested on a disease based on new insights, barely any are chosen for additional analysis. More specifically, approximately 10,000 drugs are tested, on average, in the discovery stage. Of this, around 250 continue to the preclinical stage, and only about 5 are deemed ready for further analysis in the clinical trials. 

Therefore, with this current process, there is an approximate 0.05% chance of discovering a possibly effective drug. Even so, of the scarce amount that pass to the clinical trials, even fewer advance beyond that stage to reach commercial availability. With an average success rate of drugs in clinical trials at approximately 11.1%, it can be reasonably inferred that a staggeringly low 0.005%, or 1 in 20,000 molecules tested become an actual product. 

Despite the current model’s inefficiency, until very recently there were no better alternatives. To put it into perspective, the US Food and Drug Administration (FDA) currently uses the previously described selective method. In the past few years, a more productive option has begun to emerge – artificial intelligence. 

Digital Chemistry

Figure 2: bu.edu

In a 2022 MIT study, a machine learning model was trained to suggest molecular structures that have certain properties and can be synthesized. By feeding the model with a multitude of molecules, elements, and reactions that take place to form its structure, the model learns to synthesize desired molecules independently. The trained model is then inputted with a set of “building blocks” to create a molecule (list of chemicals and their possible reactions) to restrain the search to what is possible; then, a decision tree is employed to find the final molecule. Although the model is still in development, this methodology could revolutionize the drug discovery process, and open up doors for limitless innovation in the future.

Figure 3: https://www.researchgate.net/publication/322585810_Enhancement_of_the_thermal_and_alkaline_pH_stability_of_Escherichia_coli_lysine_decarboxylase_for_efficient_cadaverine_production

One company that has also worked on utilizing artificial intelligence in drug development considerably, and currently holds the title for the “leading computational platform for molecular discovery and design” is Schrödinger. With a working procedure for molecular discovery, and several patents, this company has developed molecules that have passed the preclinical stage, and could likely be effective in treating diseases. For example, the drug SGR-1505 blocks a protein called MALT1, which is involved in growth of B-cell lymphomas (cancers of the immune system) and therefore, could be a promising way to treat those cancers. This drug was discovered through machine learning methods, and serves as a testament to the extent of the possibility in this field.

Conclusion

Traditional drug discovery, although foundational, is an extremely tedious and inefficient process that has considerable potential for improvement. To reduce the time and resources involved with this system, using machine learning procedures can significantly reduce the effort necessary to successfully achieve molecular discovery. Despite the old system still being in use, digital chemistry’s integration of machine learning and AI can potentially redefine the field entirely – a new era.

Sources:

  • https://news.mit.edu/2022/ai-molecules-new-drugs-0426
  • https://www.schrodinger.com/platform/
  • https://www.schrodinger.com/pipeline/malt1/
  • https://www.schrodinger.com/pipeline/
  • https://ftloscience.com/ai-in-drug-discovery-chemical-synthesis/
  • https://www.fda.gov/patients/drug-development-process/step-1-discovery-and-development
  • https://www.cardinalpeak.com/blog/best-practices-when-training-machine-learning-models
  • https://meilerlab.org/drug-discovery-design/
default1

The Default Mode Network: A Link to Creativity and Self-Discovery

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Introduction

Despite the substantial ongoing research in cognitive neuroscience, several questions have yet to be answered. What is the neural basis of the self? How does one’s neurobiology result in a complex being, capable of experiencing emotion and engaging in self-reflection? At what point does the  brain’s function shift from being purely biological to enabling introspection and conscious thought? Although there is not one fixed answer to these questions, many scientists over  the past decade have advanced this field of study by identifying different parts of the human brain that make up one’s identity–one of which is the Default Mode Network. 

The Default Mode Network (DMN) is a system of interconnected brain regions that are distributed throughout the cerebral cortex. When these regions work as one, their combined functions lead to creativity and self-reflection. This article will discuss the basic purposes of the DMNand how this intricate network shapes our personal experiences and identity. 

What is the Default Mode Network?

The DMN is like a switch that turns on- and off based on whether or not a task is being performed. While it is usually inactive when one’s attention is required to complete a task, such as engaging in a conversation, solving a puzzle, or exercising,  the DMN activates once tasks are complete—or when one  is  at “rest.” This encompasses all the moments when one is conscious, but not actively  thinking about any specific topic (Vessel et al.).

When the DMN is active, the mind is likely focused on internal processes, such as self-reflection, imagining the future, or recalling personal experiences. If the DMN is not properly shut off when switching to an external task, an individual  may be prone to “mind-wandering”, or becoming  distracted from their goal by unrelated thoughts. Some of the other essential functions of the DMN include pondering about oneself, social cognition, memory of specific life events, and language.

Image from https://www.simplypsychology.org/what-is-the-default-mode-network.html

The major components of the DMN are the medial prefrontal cortex (mPFC), precuneus (PCUN), posterior cingulate cortex (PCC), and the angular gyrus (ANG); each region has a unique function. The vmPFC (ventro-medial prefrontal cortex) is involved in motivation, while the dmPFC (dorso-medial prefrontal cortex) is responsible for self-referential judgment and understanding the mental states of others (Viezzer). The PCC, PCUN, and ANG contribute to a process called “autobiographical memory”, a collection of key events resembling a life story. Apart from these networks, the DMN also includes other brain regions that are involved in memory and emotions, such as the hippocampus and the amygdala.

While the basic function of the DMN holds true for most scenarios, there are many exceptions when it is active even during task performance. An experiment done by researchers at New York University shows that the DMN can be activated when one is viewing artwork. Participants in this experiment were shown pieces of art and asked to evaluate how “moving” they were, which was measured by their emotional reaction. The results showed that the DMN activates upon viewing “highly-moving” art, meaning that art elicits a strong reaction (Vessel et. al). Why would the participants’ DMN be active while they are focused on an external stimulus? The answer to that question lies in the concept of self-discovery. The art that someone is drawn to often reflects a part of them. It is possible that the DMN helped participants identify parts of themselves that were represented in the artwork, aiding the process of introspection.
The DMN’s role in self-reflection is also corroborated by the results of an experiment done by Davey et al., which revealed that the Default Mode Network is engaged with making self-referential judgements. Individuals were presented with various personal qualities (e.g. “skeptical”, “perfectionistic”) and asked how well they thought each described them. The fMRI data collected indicated that the DMN was more active when performing this self-referential task than an externally based activity (Davey et al.). Similarly to the previous experiment, this finding reinforces that the DMN is essential for shaping one’s identity.
Moreover, neuroscience researcher Vinod Menon from Stanford University suggests that when the functions of DMN regions overlap, a unique “internal narrative” is created. The “internal narrative” consists of personal values and beliefs, memories of major events, facts about oneself and the surrounding world, as well as the ability to reason (Menon). In other words, the DMN’s functions configure patterns of thought in human-beings and are central to our perception.

Applications of the Default Mode Network to Creativity and Self-Discovery

The default mode network plays a major role in shaping one’s personal story. Whether an individual is reflecting on their dreams or contemplating their favorite music genres, the DMN serves as a gateway to understanding one’s deepest values and ambitions.
This elaborate connection of brain regions can also serve as a starting point for creativity. The beliefs one collects throughout their life can easily seep into their thought process. Although one’s spontaneous thoughts are easily dismissed as insignificant distractions, the “stream of consciousness” has hidden potential, as spontaneous thoughts tend to be the most innovative. Taking the time to deliberately explore these thoughts can uncover hidden ideas, whether they hold an unconsidered perspective or a novel solution to a previously “impossible” problem. So, the next time the human mind decides to wander off, take a second to entertain those “distracting” thoughts–perhaps an innovative, fruitful idea may come to light.

Credits:

Cover Image from: https://www.it-team-paws.com/navigating-mental-health-through-self-discovery/

Davey, Christopher G., et al. “Mapping the Self in the Brain’s Default Mode Network.” NeuroImage, vol. 132, May 2016, pp. 390–397, www.sciencedirect.com/science/article/pii/S1053811916001294, https://doi.org/10.1016/j.neuroimage.2016.02.022.

Menon, Vinod. “20 Years of the Default Mode Network: A Review and Synthesis.” Neuron, vol. 111, no. 16, May 2023, www.med.stanford.edu/content/dam/sm/scsnl/documents/Neuron_2023_Menon_20_years.pdf, https://doi.org/10.1016/j.neuron.2023.04.023.

Shofty, Ben, et al. “The Default Network Is Causally Linked to Creative Thinking.” Molecular Psychiatry, vol. 27, no. 3, 1 Jan. 2022, pp. 1848–1854, https://doi.org/10.1038/s41380-021-01403-8.

Vessel, Edward A., et al. “Art Reaches Within: Aesthetic Experience, the Self and the Default Mode Network.” Frontiers in Neuroscience, vol. 7, 2013, https://doi.org/10.3389/fnins.2013.00258.

Viezzer, Sara. “What Is the Default Mode Network?” Simply Psychology, 3 Mar. 2023, www.simplypsychology.org/what-is-the-default-mode-network.html.