BioQuakes

AP Biology class blog for discussing current research in Biology

Author: itsalive

Of Mice and Menin; New Research Provides Answers to Aging

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On April 23, 2023

In Student Post

A Decline in Hypothalamic Menin Drives the Aging Process, and Dietary Supplement can Reverse it in Mice

A new study published by Lige Leng of Xiamen University, Xiamen, China, and colleagues on March 16th, 2023 reveals a possible link between the decline in hypothalamic Menin and aging. These findings revealed a previously unknown driver of physiological aging, and now suggest that the addition of a simple amino acid may reduce age-related changes.

“We speculate that the decline of Menin expression in the hypothalamus with age may be one of the driving factors of aging, and Menin may be the key protein connecting the genetic, inflammatory, and metabolic factors of aging” – Leng

The hypothalamus is known to be a key mediator in physiological aging. Over time its tissue becomes inflamed, thereby causing an increase in neuroinflammatory signaling. The inflammation then spreads to the brain and the periphery of the nervous system, promoting aging-related degenerative diseases. Leng’s research showed that Menin, a hypothalamic protein, is an inhibitor of hypothalamic neuroinflammation, therefore inferring a negative correlation between the quantity of Menin and aging processes. 

Mice in the laboratory

Leng observed that Menin in the hypothalamus declines with age. Leng and his colleagues devised an experiment using conditional knockout mice, in which Menin activity could be inhibited. They recorded that Menin-deprived younger mice had an increase in hypothalamic neuroinflammation, aging-related phenotypes including reductions in bone mass and skin thickness, cognitive decline, and modestly reduced lifespan. To fully understand the effects Menin has on aging, Leng “flipped” the experiment and delivered the gene for Menin to elderly mice. Thirty days later, they found improved skin thickness and bone mass, along with better learning, cognition, and balance.

3u84menin

3D rendering of Menin

Connection to AP Bio

Menin is a scaffold protein. One of its many functions is to upregulate the expression of cyclin-dependent kinase (CDK) inhibitors, thereby reducing beta-cell proliferation. This inhibition causes the cells to stop developing after G1. This then halts the entire process of cell division, as the cell cannot replicate its DNA and go through mitosis. 

CRISPR Provides New Hope for those with Huntington’s Disease

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On March 1, 2023

In Student Post

Intro

Neuron with mHtt inclusion

Neurons transfected with a disease-associated version of huntingtin

Huntington’s disease is a neurological disorder that affects the basal ganglia and cerebral cortex of the brain. These areas of the brain are associated with movement, learning, thinking, planning, motivation, and emotion. Huntington’s disease is caused by a single mutation in the huntingtin (HTT) gene, afflicting more than 200,000 people worldwide and 30,000 in the United States. There was believed to be no cure, however, novel research regarding CRISPR gene editing is giving those who suffer from this condition new hope. 

Identifying the problem (and connection to AP Bio)

“Our cells have a hard time copying repetitive DNA, and these copying errors can cause repetitive sequences to grow longer with each generation,” (Gene Yeo, PhD). 

Huntington’s disease is caused by repetitive and damaging sequences in the HTT gene. Within the cell cycle, in order for the cell to divide into two daughter cells during mitosis, the cell’s DNA must be replicated in the synthesis phase. In Huntington’s disease, the damage done to the HTT gene is carried through the synthesis phase, causing everlasting effects on future generations of cells. These repeated genes amass to many times their normal length and result in toxic clumps which aggravate the striatum of the brain which is important in regulating movement; thereby leading to Huntington’s Disease. 

Inventing a solution

CRISPR is a tool that edits genomes by precisely cutting DNA and then letting natural DNA repair processes take over. The system consists of two parts: the Cas9 enzyme and a guide RNA. CRISPR illustration gif animation 1In this new study, Gene Yeo and his team of researchers at the University of California San Diego School of Medicine are using RNA-targeting CRISPR/Cas13d technology to develop a new therapeutic strategy that specifically eliminates toxic RNA that causes HD. Yeo delivered the CRISPR therapy through viral vehicles to neuronal cultures grown from the stem cells of an individual with Huntington’s syndrome. His team has found that the approach not only targeted and destroyed mutant RNA molecules but also cleared out toxic protein buildup without disrupting other genes. 

Predictions for the future

Black-mouse-in-purple-gloved-hands-2Yeo’s team collaborated with Wenzhen Duan’s team at Johns Hopkins to conduct preclinical testing in mice. They found that the CRISPR therapy improved motor coordination, attenuated striatal degradation and reduced toxic protein levels in a mouse model of HD. The therapy lasted for at least 8 months and caused minimal effects on other RNA molecules. Although a mice’s anatomy is nowhere near as complex as a human’s, this new research gives incredible insight into the future that CRISPR holds and how impactful its use can be.

Anxiety vs Sleep, A Battle of the Sexes

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On January 16, 2023

In Student Post

Overview

A new discovery has been made which may help explain the higher prevalence of sleep disruption and anxiety in women, not only leading to better treatments for anxiety and sleep but also strengthening our understanding of how the brain varies between the two sexes.

What We Know vs What We Don’t

Insufficient sleep is already known to be a cause of anxiety. However, this might not be the case for everyone, or at least to the same extent. When considering sex, “women are proven to experience a greater anxiogenic impact in response to sleep loss than men”. Yet it is unknown which regions of the brain govern sleep-loss-induced anxiety and how these regions’ reactions differ between men and women. A team of scientists led by Andrea N. Goldstein-Piekarski is attempting to find answers by using structural brain morphology. This method will allow them to link anxiety caused by sleep deprivation to the volume and shape of “emotional” regions of the brain between the two sexes.

ANXIETY

Statistical Analysis

Using an ANOVA approximation with the equation below, the scientists were able to decipher whether the amount of anxiety reported via the PSG test for each of the sleep conditions is related to sex and the grey matter volume of the individual’s brain.  

(sleep-deprived[morning-evening]  – sleep-rested[morning-evening]anxiety ~ sex × grey matter volume)

Women demonstrated a significant Time × Condition interaction, expressing a nearly fourfold increase in anxiety on the sleep deprivation night relative to the full night of sleep in morning-evening anxiety. There was no Time × Condition interaction for men in morning-evening anxiety, however, some individuals did experience an anxiogenic response, indicating that this specific consequence of sleep loss is not completely sex-based.  

Women demonstrated a significant negative association between anxiety and gray matter volume in the emotion generation and integration region of the insula/

Gray743 insular cortex

IFG and a marginally significant negative association in the lOFC, which means that gray matter volume did not influence the women’s anxiogenic responses. This incredibly opposes men who, on average, demonstrated significant positiveassociations in the insula/IFG and lOFC. Therefore, although men as a whole did not demonstrate a significant increase in anxiety due to sleep deprivation, the variance of anxiogenic response in men was indeed related to variation in gray matter volume of these regions. 

 

Conclusion

These findings show that women do indeed experience more significant anxiogenic responses to sleep deprivation than men. They also show that the morphology of emotion-relevant regions can explain the variance and vulnerability of men to anxiogenic reactions to sleep deprivation. 

What Now?

Such findings suggest that for women especially, targeted sleep restoration may offer a novel, non-pharmacological therapeutic pathway for ameliorating anxiety. This research can also improve public health awareness about the importance of sleep, especially for those who are at a greater risk of anxiety disorders. 

Connection to AP Bio

Research from Johns Hopkins has shown that the anxiety and stress response can often lead to mitochondrial damage. Since anxiety and stress can cause the physical symptoms of increased heart rate and breathing, the mitochondria are pushed to provide more energy through cellular respiration. This can be detrimental to an individual who is in a constant state of stress and anxiety as the mitochondria have very little repair mechanisms, which would then harm the body’s overall production of energy. In relation to the study, this information conveys that sleep deprivation not only affects mood and physical performance but also organelles and basic cellular functions.

Dictionary

  • Structural Brain Morphology – the study of the structural measures of the brain, e.g., volume and shape 
  • Vulnerability Biomarker – any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease (WHO)
  • Anxiogenic – producing anxiety 
  • ANOVA – an analysis of variance between more than two groups
  • Polysomnography (PSG) – a test conducted to diagnose sleep disorders

Winter is Coming, and so is BQ.1 and BQ.1.1

By

On December 6, 2022

In Student Post

Winter is Coming

“The U.S. is going to see a winter surge in COVID infections,” predicts William Hanage, an epidemiologist at the Harvard T.H. Chan School of Public Health. “And I think that if nothing else changes BQ.1 and BQ.1.1 are likely to be very significant players”.

Two new omicron subvariants – BQ.1 and BQ.1.1 – are becoming dominant in the United States, causing fear of another COVID-19 surge as people prepare to gather for the winter holidays. These subvariants appear to be the most adept yet at evading immunity from vaccination and previous infection. 

Mutations in Spike Proteins

New mutations in the virus’s spike protein appear to make BQ.1 and BQ.1.1 as much as seven times more ‘immune evasive’ than past variants. Spike proteins are the antigens on the surface of the COVID-19 virus. A mutation in the spike protein is an issue because the body’s immune system creates antibodies to fend off foreignSARS-CoV-2 without background invaders specific to that antigen. Memory helper T and B cells then keep these antibodies within the body in the case of a secondary exposure, which would then cause a faster, stronger, and longer immune response. Because the spike proteins are mutated, the body needs to reenact the process of producing antibodies, which could take a long time to have a noticeable effect on the body’s immune system, therefore increasing concern for the individual’s overall health. 

A Closer Look at the Mutation (RBD)

The specific site of the mutation in the BQ.1 and BQ.1.1 variants is the receptor binding domain (RBD) which allows [the virus] to dock to body receptors to gain entry into cells and lead to infection; in other words, the RBD is the target of antibodies that deliver a potent immune response. Researcher Cao and his teamStruktura SARS-CoV 2 believe that the RBD mutations allow the variant to evade infection-blocking ‘neutralizing’ antibodies that were a response to previous COVID-19 vaccines and exposure to earlier Omicron variants, such as BA.2 and BA.5. There seems to be a direct correlation between the RBD changes and the faster it spreads both within the body and the population. This is where BQ.1 and BQ.1.1 differ; variants, such as BQ.1, with five key RBD changes (relative to BA.2) seem to be growing in number at a slower rate than variants with six changes. A descendant of BQ.1 called BQ.1.1 has six such changes, and is rising rapidly across Europe, North America and other places.

Double Immunity?

Another variant of COVID-19, XBB, is predicted to “gain an edge” against BQ.1.1 because it has seven changes in its RBD, allowing it to grow at an even faster rate. Although there is currently no data to back up the theory that double immunity could be at play, researcher Cao and his team have a feeling that if you’re infected with BQ.1, you might have some protection against XBB.

How to Stay Safe

Although there is never a 100% guarantee that you won’t catch BQ.1, BQ.1.1, or XBB, there are preventative measures you can take to decrease your chances. As we have been advised since the start of COVID, one should continue to stay sanitary, wear a mask if in a susceptible/crowded place, and be updated on new vaccines. Winter is coming, and it is time to fortify and protect yourself against what lurks beyond your body’s walls.

Xylem Filters Engineered to Remove E. Coli: A Possible Solution to the Deadly Bacteria?

By

On October 19, 2022

In Student Post

Overview

Novel research has proven that filters made from xylem in trees can be used to remove bacteria and pathogens from drinking water, leading to a possible solution for the worldwide E.coli crisis.

Intro

Great Pine Tree In Vozdvizensky Forrest

Pine Tree

Nonflowering trees, such as pine and ginkgo, contain sapwood lined with straw-like conduits known as xylem. Xylem is a vascular tissue found in plants that provides structural integrity and carries water and minerals from the roots to the rest of the plant. Xylem tissue is made of specialized cells which are water-conducting, allowing for the water molecules to adhere to its tissue as it is being pulled up the plant. Water passes through Xylem’s conduits which are interconnected via thin membranes that act as natural sieves, filtering out bubbles from water and sap. Inspired by this natural phenomenon, a study published by the Massachusetts Institute of Technology engineered a filter made of xylem that successfully removes E. coli from drinking water.

 

 

“Two Birds With One Stone”

Xylem Stained

Stained Xylem Cross-Section

One major problem that the engineers ran into was dryness and its effect on the xylem’s permeance: as the wood dried, the branches’ sieve-like membranes began to stick to the walls, reducing the filter’s permeance, or ability to allow water to flow through. Another problem found was that the filters would erode and degrade with use, causing a build-up of woody matter which clogged its passageways. The engineers were able to solve both of these problems by cutting the xylem into small cross-sections, soaking them in hot water and then in ethanol, and letting them dry. Now, the filters were ready to be used. 

In Action 

The engineers quickly sprang into action and brought their invention to India for testing; India holds the highest mortality rate due to water-borne disease in the world, where safe and reliable drinking water is inaccessible to more than 160 million people. Their trials in India provided them with beneficial feedback regarding replacement frequency and the comfortability of the product being natural and recognizable. With this criticism and assurance in mind, they crafted a new prototype and are now hoping to produce these on a massive scale so that all can have access to clean water.

Escherichia coli electron microscopy

E.coli Electron Microscopy

Urgency 

A study published by the International Journal of Environmental Research and Public Health concluded that safe drinking water for all is one of the major challenges of the 21st century and that microbiological control of drinking water should be the norm everywhere. E. coli infections cause approximately 265,000 illnesses and about 100 deaths in the US and greater than 300 million illnesses and nearly 200,000 deaths are caused by diarrheagenic E. coli globally each year worldwide. It is imperative that this filter be mass-produced and utilized nationally in order to prevent further deaths and guarantee clean water to everyone across the globe. 

Transpiration of Water in Xylem

Transpiration of Water in Xylem

Relation to AP Bio 

This topic is closely related to the adhesive and cohesive properties of water. In plants, water adheres to the xylem as it is brought up from the roots and dispersed throughout the plant. Water also coheres to itself, allowing for more than one molecule to move up at a time and therefore causing a cascade of molecules to follow in one’s path. If it were not for this property of water, plants would not have evolved xylem and therefore this filtration innovation would not exist. 

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