Category Archives: Daily Science

Everyone has heard that too much stress will cause grey hair. This is easily seen in former president of the United States, Barack Obama, whose hair could not escape the stress of the Oval Office! But what exactly links grey hair and stress? This year, researchers at Harvard University found that the nervous system eliminates pigment-regenerating stem cells responsible for coloring our hair!

THE ROOT OF THE PROBLEM

When you are stressed, your body responds in three distinct ways: the activation of your immune system, the activation of your sympathetic nervous system (SNS), and the release of cortisol, an energy-stimulating hormone. All these responses put your body into a “fight or flight” mode; increasing heart rate and blood pressure. The challenge for Zhang’s team was to sort through these three responses and determine which caused grey hair.

Zhang’s team tackled this problem by performing a series of experiments on black-furred mice. They first tested if immune system activation was the cause by seeing if the fur greyed under stress, even when the immune system was deactivated. They indeed found that stressed immune-deficient mice still greyed, indicating that stress causes greying, independent of an immune response.

They also ran similar experiments using mice mutated to not respond to cortisol or noradrenaline, a molecule involved in SNS activation. The idea being that if  a response was involved, stress should not cause the fur to grey if it was removed. In mice lacking response to cortisol, the fur still greyed; however, in mice lacking the response to noradrenaline, their fur remained black! This indicated that the SNS was the main driver in hair greying.

ZOOMING IN FURTHER…

With the culprit in hand, Zhang’s team didn’t just stop there! Through further experimentation, they illustrated that the SNS over-stimulates MeSC, the stem cells involved with hair pigmentation. During hair growth, these MeSC cells transform into pigment-producing cells and color the hair. Under stress, the SNS causes these MeSC cells to transform at an abnormally high rate, quickly depleting these cells and leading to grey hair.

THE REASON BEHIND THIS LINK?

In truth, the reason why this MeSC and SNS interaction exists is unclear. Zhang’s team suggests an evolutionary perspective. Since octopuses, a distant relative to mice and humans, can modify pigmentation of their skin using the SNS, they hypothesize that this interaction was simply conserved. Whatever the reasons may be, this just further shows that the mystery has yet to be completely solved!

We’ve all heard it endlessly as kids. Don’t eat too much sugar, it’s bad for you. However, what if I told you that sugars aren’t all that bad and in fact, careful changes to its chemistry can lead to life-saving drugs, such as antibiotics! Just last year, researchers at the University of British Columbia, led by Stephen Withers, found a unique way to tinker with sugars’ chemical structures by using molecules in bacteria. The same bacteria found in our poop!

A view of E. Coli, the bacteria that was used by Wither’s and his team. Credits: The Philadelphia Inquirer

SWEET…BUT WHAT ARE THEY?

Before we go further, let’s start with a simple question: What exactly are sugars? Sugars are molecules shaped like hexagons which are often joined to other molecules known as “acceptors”. In a way we are kind of like sugars; we find someone we like, confess how we feel, and they accept our love! Right? Wrong. As we all know the last part rarely happens and this is the same in sugars, as chemists have yet to find easy ways to join the sugar and acceptors. Luckily for sugars (and unluckily for us), Mother Nature has come up with some solutions, using helper molecules known as enzymes.

Curious as to what type of sugars chemists work with? There’s no ambiguity here, chemists use the same molecules found in sugar cubes. Yes! The ones you put in your coffee. Credits: The Verge

A SOLUTION UNDER OUR NOSES…

Instead of struggling to find ways of joining sugars and acceptors, Wither’s team thought: Why not just use these enzymes? In other words, hijack Mother Nature. To make their idea a reality, they extracted sugar-specific enzymes from E. Coli, a bacterium that lives inside the human digestive tract. Their efforts gave them 175 sugar-specific enzymes, and from this they chose 8 enzymes that were most specific to the type of sugars and acceptors they were interested in.

“With the 8 enzymes in hand, Withers and his team could now easily make these sugar-acceptor linkages” is what I would like to report; however, things are never so simple. It turns out that the sugar-specific enzymes they got from E. Coli did the exact opposite of what they wanted. Instead of forming sugar-acceptor linkages, they were specialized in breaking them.

Unsurprisingly the savvy researchers expected this and already had a reliable strategy to reverse-engineer these enzymes from linkage breakers to linkage makers. You may be wondering how they re-purposed something to work completely opposite of what it was intended for. To reconcile this, think of this example: hammers. If you’re feeling angry one day you would likely use the hammer to smash things. However, if you’re feeling innovative one day, the hammer would help you build things by hammering in nails. These enzymes are similar; an enzyme that breaks sugar bonds differs very little from one that builds sugar bonds.

MORE THAN JUST A BOND…

Sugars go way beyond than just satisfying your sugar fix. They are molecules essential to the maintenance and regulation of not only your body, but in most living things! Because they are found everywhere, including infectious bacteria, sugar-based molecules serve as effective antibiotics, however making these drugs are difficult. Why? Well as mentioned before, chemists have trouble making these sugar-acceptor bonds; however, the research done by Wither’s team show that this will not remain the case. On a lighter note, they also created a sugar-based molecule that had nothing to do with health; detergent. This just further shows that these bonds are far-reaching and relevant in many contexts.

Story source

Armstrong, Z.; Liu, F.; Chen, H.-M.; Hallam, S. J.; Withers, S. G. Systematic Screening of Synthetic Gene-Encoded Enzymes for Synthesis of Modified Glycosides. ACS Catalysis 2019, 9 (4), 3219–3227.

There may be hope for people suffering severely from COVID-19. On July 28 2020, Health Canada has approved the use of Remdesivir for critically ill COVID-19 patients.

how does it work?

Remdesivir is an antiviral drug that acts as an inhibitor. Basically, the COVID-19 virus uses a protein complex called RdRp to replicate its genetic material and further infect the body. Since Remdesivir inhibits RdRp, the virus can no longer replicate and the infection is impeded.

proof that it works

A double-blind, randomized, placebo-controlled trial was conducted on 1063 patients suffering from COVID-19. The results of this trial showed that those who took the drug recovered 4 days faster than those who didn’t. They also found that lung infection in treated patients were significantly better than those who didn’t get the treatment.

who can use this drug

This drug isn’t for every COVID-19 case. You need to present severe symptoms such as pneumonia and require extra oxygen to help breathe (respiratory machine). The safety and effectiveness of the drug also needs to be further evaluated. To this end, Health Canada has authorized two clinical trials to gather more data.

SSRIs (selective serotonin reuptake inhibitors) are among the most commonly prescribed medications, used as a first-line pharmacological treatment for depression. Their basic mechanism is well-known: blocking the serotonin transporter, resulting in decreased serotonin reuptake into the neuron and thus more serotonin remains outside, allowing for more activation of serotonin receptors, and thus decreasing the depressive symptoms [1]. However, this is an oversimplification: the role of serotonin in the brain is still poorly understood.

For example, abnormally large serotonin levels in the brain may result in serotonin syndrome, a life-threatening condition characterized by neuromuscular and autonomic hyperactivity [2]. This condition may be caused by the use of drugs that act on the serotonergic system, such as SSRIs. On the other hand, serotonin deficiency may also lead to hyperactivity, as well as disrupted sleeping patterns [3].

There are also a multitude of serotonin receptors in the brain, all with different effects [1]. For instance, activation of the 5-HT1A receptor with selective agonists results in antidepressant effects [4]; however, blockade of 5-HT2C receptors with selective agonists also results in antidepressant effects, with a faster onset [5]. As well, autoreceptors modulate serotonin signalling, which further complicates the effects of increasing serotonin levels. Interestingly, the downregulation of 5-HT2C receptors appears to coincide with the onset of effects from SSRIs [6], suggesting that some abnormal signalling involving the 5-HT2C receptors may be involved in depression.

Further complicating matters is the downstream effects on serotonergic, noradrenergic, and dopaminergic pathways. It is known that NDRIs (norepinephrine/dopamine reuptake inhibitors) such as buproprion are also effective in treating depressive symptoms [7], and that activation of serotonin receptors also results in modulation of norepinephrine and dopamine signalling, such as in the case of 5-HT2C receptors [6]. This is still an active area of research, but it is still quite clear that the role of serotonin in the brain is not as simple as “serotonin = happy”.

References

[1] Sangkuhl K, Klein T, Altman R. Selective Serotonin Reuptake Inhibitors (SSRI) Pathway. Pharmacogenet Genomics. 2009;19(11):907-909. doi:10.1097/FPC.0b013e32833132cb

[2] Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin Syndrome. Ochsner J. 2013;13(4):533-540.

[3] Whitney MS, Shemery AM, Yaw AM, Donovan LJ, Glass JD, Deneris ES. Adult Brain Serotonin Deficiency Causes Hyperactivity, Circadian Disruption, and Elimination of Siestas. J Neurosci. 2016;36(38):9828-9842. doi:10.1523/JNEUROSCI.1469-16.2016

[4] Kennett GA, Dourish CT, Curzon G. Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. Eur J Pharmacol. 1987;134(3):265-274. doi:10.1016/0014-2999(87)90357-8

[5] Opal MD, Klenotich SC, Morais M, et al. Serotonin 2C receptor antagonists induce fast-onset antidepressant effects. Molecular Psychiatry. 2014;19(10):1106-1114. doi:10.1038/mp.2013.144

[6] Millan MJ. Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005;60(5):441-460. doi:10.2515/therapie:2005065

[7] Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. Ther Adv Psychopharmacol. 2016;6(2):99-144. doi:10.1177/2045125316629071

COVID-19 needs no introduction, the familiar spiky ball has been tormenting us since the beginning of 2020. Consequently, researchers around the world have been working to find a vaccine and one potential solution seems rather odd. UBC researchers, led by Josef Penninger, have found that administering ACE2 decreases the virus’ infectiousness. The odd part? ACE2 is the same protein on lung cells exploited by COVID-19 to gain entry into these cells.

COVID-19 structure. The red blobs coating the virus are Spike Glycoproteins, which facilitate infection of cells. Credits: Newscientist

Infecting the lung cells…

One of main targets of COVID-19 is the lungs. This is because the surface of the lung cells are coated in ACE2 proteins. On the surface of COVID-19 there are Spike Glycoproteins, which recognize and bind ACE2 proteins, facilitating infection of the lung cells (see our previous post for general information on COVID-19). Tinkering with this ACE2 – Spike Glycoprotein interaction is the goal of many developing vaccines and was also what Penninger’s team targeted.

satisfying the virus stops the infection!

The way Penninger’s team approached this problem was truly ingenious. Since the Spike Glycoprotein binds to ACE2 on the cells, why not just administer an outside source of ACE2, so the Spike Glycoprotein can bind to those instead? The administered ACE2 would effectively bind to all the Spike Glycoproteins on the virus, rendering it inactive and unable to target cellular ACE2.

They researchers tested this theory by infecting cell cultures with COVID-19. They showed that by incubating these cultures with hrsACE2 (genetically modified ACE2), the virus growth was inhibited.

To take it a step further, the researchers grew blood vessel and kidney organoids, which are models of these respective organs. Upon administering hrsACE2, infection and spread of COVID-19 in these organoids were significantly reduced. This demonstrated that hrsACE2 could inhibit infection in human organs!

Spike Glycoproteins on COVID-19 will bind to hrsACE2 instead of cellular ACE2 – inhibiting infection. Adapted: Penninger et al. (2020)

More work is still needed

Although the results are promising, Penninger’s team caution that there are still some kinks that need to be worked out:

The inhibition [by hrsACE2] is not complete […]. This may be due to […] other co-receptors/auxiliary proteins or even other mechanisms by which viruses can enter cells.

They also suggest that future studies should look at the systems that model the lung, as this organ is the primary infection target. With all this being said, Penninger’s research is still without doubt groundbreaking, and a big push forward into getting rid of this virus once and for all.

Journal Reference

Monteil, V., Kwon, H., Prado, P., Hagelkrüys, A., Wimmer, R. A., Stahl, M., . . . Penninger, J. M. (2020). Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell, 181(4), 905-913.e7. doi:10.1016/j.cell.2020.04.004

Have you ever watched a movie in 3D at a movie theatre? You probably had to wear special glasses in order to get that 3D effect. And if you take them off, the movie looks completely blurry.

The most common way of producing the 3D image is through the use of polarized filters. This principle works by projecting the movie from two different perspectives at the same time, with the light being polarized in a different way in each projection. The polarization refers to the orientation the waves are travelling in, which means multiple light waves of different polarizations can be still travelling in the same direction! Continue reading →

Have you eaten any fried potato product recently? You do know how unhealthy those things are, right? Not only because of the fat and carbohydrate and sodium content, but possibly because of the presence of acrylamide. Acrylamide is a potent neurotoxin and a possible carcinogen, which is often used in laboratories for making gels to separate proteins. [1]

Potato chips, also known as potato crisps, are a fried potato product that may have unhealthy levels of acrylamide. Credits: Wikimedia

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