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Researchers find four new drug candidates to tackle Huntington's disease

There is currently no approved treatment for the reversal of Huntington's disease

Satarupa Bhaduri

Cell Biology

University of California, San Diego

Huntington's disease is an inherited neurodegenerative disorder which leads to the progressive deterioration of movement, cognition and behavior. In the US, 30,000 people are living with Huntington's disease, and another 200,000 individuals are at risk, where symptoms can start at any point between childhood to advanced age. While approaches such as speech and physical therapy, antidepressants and antipsychotics have been adopted to slowing down disease progression, there is currently no approved treatment for the reversal of the disease. Recently, a drug has entered clinical trials and results are awaited with bated breath.

In the human body, misfolded or dysfunctional proteins are engulfed by structures called autophagosomes, which target such proteins for degradation via a pathway called autophagy. Here, Huntington's disease is caused by a mutation in the HTT gene, which encodes a protein called Huntingtin (HTT). This mutation allows the HTT protein to escape autophagy, and instead accumulate and destroy neuronal cells found in the brain over a period of 10-25 years. 

In a recent study published in Nature, researchers have identified four synthetic organic compounds which link the mutant HTT to a protein called LC3 which is present on autophagosomes, thereby ensuring the removal of the mutant HTT by autophagy.

These four compounds lowered the levels of the mutant HTT protein by approximately 30% in comparison to normal HTT, when tested in different mediums — specifically in vivo in Drosophila fly and mice models of Huntington's disease, and in vitro on cultured neuronal cells obtained from mice and individuals with Huntington's disease.

In addition, these compounds are specific for the mutated portion of the Huntingtin protein as they could potentially attack another similarly mutated protein called Ataxin-3, which happens to cause spinocerebellar ataxia — an incurable neurodegenerative disease. The compounds were even capable of reversing the disease symptoms in both Drosophila flies and mice. Here, the affected flies and mice on treatment with the compounds displayed significant improvement in behavioral and movement deficits measured by tests such as whether the Drosophila could fly, and how well mice were able to balance and display gripping force.

These four synthetic compounds serve as promising candidates for future drug discovery research in this field. The study also opens the field for targeting several proteins which accumulate the same kind of mutation, leading to severe neurodegenerative disorders.

How many things can scientists name -Seq? Let us count the ways

From lettuce to cat poop to human cells, we're ready to sequence it all

Farah Qaiser

Molecular Genetics

University of Toronto

In the past decade, scientists have been slowly sequencing everything — and yes, I mean everything. Scientists have sequenced romaine lettuce to detect food-borne pathogen outbreaks, increasing numbers of people across the world to address under-representation in genomics, and even kitty poop to better understand the cat microbiome.

But in the midst of all these sequencing studies, what sticks out to me the most is how often scientists find a way to use the word -Seq when naming new methods. Here, Seq is short for sequencing, and is often used to name experiments which involve high-throughput sequencing.

So here's a list of the many ways scientists have managed to incorporate the word -Seq when naming new methods. It certainly isn't comprehensive, and doesn't include every -Seq method out there, but here it is anyway.

Here are (some of) the ways you can sequence DNA

scientific instrument

 The Oxford Nanopore MinION is a pocket-sized DNA sequencer  — just in case you want to sequence on the go.

Oxford Nanopore Technologies

There are so many different aspects of biology to consider today when it comes to sequencing DNA. Are you interested in learning what DNA interacts with? Try using ChIP-Seq to explore protein-DNA interactions, or if you want to get more specific, use MAINE-Seq to find DNA bound by histone proteins.

Interested in the regulatory regions of the genome? There's also FAIRE-Seq to identify regulatory regions in the human genome, and 4C-Seq to characterize how DNA is physically organized around regulatory elements. Or perhaps you're interested in whether DNA is methylated or not? If so, you can take your pick between BS-Seq, BisChIP-Seq, Methyl-Seq and so many more.

Want to look at RNA? There's a -Seq for that, too

The first step to building a protein in your cells is to transcribe DNA into RNA (ribonucleic acid). Scientists can map RNA using RNA-Seq, but that's not all. Check out RIP-Seq to find out where RNA-protein complexes are, dsRNA-seq to investigate double-stranded RNA molecules, and structure-Seq to find secondary RNA structures across the genome. There's even single-cell RNA sequencing (scRNA-seq) if you want to look at individual cells, which was hailed as Science's Breakthrough Of The Year in 2018. Fun fact: scRNA-seq was originally called mRNA-Seq, but perhaps that name wasn't catchy enough.

cartoon of the chemical structure of RNA

Sponk on Wikimedia Commons

Don't forget about CRISPR!

Scientists can use the CRISPR/Cas system to edit genes, but it doesn't always work out effectively. So why not use GUIDE-Seq to identify all the double-stranded breaks introduced by CRISPR/Cas enzymes? Or Digenome-Seq to capture off-target CRISPR effects in human cells? Or perhaps CIRCLE-Seq to capture off-target effects in vitro? Or...okay, I'll stop now. But there are so many more -Seq methods out there as the scope of sequencing continues to expand.

But let's face it: I also carry out DNA sequencing to better understand complex neurological disorders. If I ever developed a method, I'd try to find a way to fit -Seq in too when naming it. How else would you know that sequencing was involved?

Why did blue whales get so big when their prey is teeny tiny?

When the food source is abundant, animals with bigger mouths can consume more calories.

Marie Claire Chelini

Evolutionary Biology

University of Nebraska – Lincoln

When we think of large animals, whales immediately come to mind. Whales come in all sizes, though. Why aren’t dolphins and orcas (which are technically toothed whales) as large as blue whales? And how come blue whales, the largest of all animals, survive on the tiniest of prey items, such as krill? A new study published in Science explores these questions.

Amanda Slater via Flickr

Being so large could help whales dive deeper and for longer, which could be good for finding large prey. Yet, for toothed whales, such as sperm whales and porpoises, such large prey is rare and hard to find. This means that, although larger toothed whales can dive deeper, their prey/dive ratio is smaller than that of smaller whales. For baleen, filtering whales, however, the story is different. There is plenty of krill in the ocean. One of the main constraints to eating, for baleen whales, is to open their mouths wide enough to swallow massive amounts of krill-containing water. And guess who has bigger mouths? Bigger baleen whales.

For baleen whales, feeding efficiency increases with mouth size, which in turn increases with large body sizes. Huge baleen whales can swallow more calories per dive than their smaller cousins. Why aren’t blue whales even bigger, then? Scientists think that it is probably due to seasonal shortages in krill density. During dry spells, fat energy storages would probably not be enough to sustain an even bigger whale. 

For toothed whales, on the other hand, being very large is not really an advantage, since there are very few large prey to be found in the ocean. It’s more energetically advantageous for these toothed predators to be medium size and eat medium size prey, than to dive long and deep searching for an elusive large meal. 

Go to bed: sleep deprivation changes how you experience pain

New research highlights the role of the nucleus accumbens in how sleep-deprived individuals respond to pain

Kamila Kourbanova

Neuroscience and Molecular Biology

Johns Hopkins University

We have all felt the sensation of pain. And we are also all familiar with sleep, a necessary bodily process, has cognitive and physiological functions. While sleep is behaviorally regulated, research shows that poor sleep can actually tamper with our brain's processing of pain. Using fMRI imaging, scientists have now visualized the amplification of the pain signal in the somatosensory cortex of sleep deprived individuals. 

The somatosensory cortex is the area of the brain that registers pain stimuli, meaning it tells us where the pain sensation we feel is coming from. Then, the pain signal moves into the insula, the part of the brain which integrates all incoming signals and creates our conscious perception of pain. Following that, the signal is sent along to the nucleus accumbens (NAcc) which plays a major role in decision-making, reward, and pain evaluation. 


The study, published last year in the Journal of Neuroscience, found that the activity of the NAcc in sleep deprived individuals is altered: compared to the pain response in people who aren't sleep-deprived, the NAcc dulls incoming pain signals, increases pain-relief seeking behavior and affects decision-making. 

A previous study highlighted the increase of opioid consumption in burn patients after just one night of interrupted sleep, which reinforces the idea that sleep and our sensations of pain are closely linked. While research strongly supports the idea that sleep deprivation does increase pain, but exactly how our brains process the interplay of sleep and pain is still being investigated. For instance, the NAcc has broad connectivity with many regions of the brain including the prefrontal cortex, anterior cingulate cortex, and the amygdala (just to name a few). Future research should tease apart the question of “What’s more important: the amount of sleep we get or the quality of sleep?” 

But in the meantime, consider counting sheep an aid to resetting our bodies and our brains. 

Scientists, beware of the consequences of routine practices in your lab!

The harmless practice of using parafilm to seal agar petri dishes containing the model organism, C. elegans, actually impacts larval development

Matthew Vandermeulen

Biology

University at Buffalo

What if some of your common practices in the lab were actually having a significant effect on your results...and you just didn’t know about it? Recently, a group of researchers from Utica College found that the practice of using parafilm to seal agar petri dishes containing the model organism, Caenorhabditis elegans, actually has a significant effect on its early development.

C. elegans is a nematode and a well-established model organism which is often used to model various aspects of development. This organism is often grown on Nematode Growth Media (NGM) agar in a petri dish.

Image of the model worm C. elegans

Meet Caenorhabditis elegans — a common model organism used in biological sciences.

NGM can sometimes dry out or become contaminated by microbes, so to prevent this, researchers often wrap up the petri dish with parafilm, the way you wrap up food containers with plastic wrap in the kitchen. This practice has been used for a long time, however, it has never been fully explored to see if it actually affects nematode development. In this study, researchers tackled this very question and investigated whether wrapping NGM agar plates with parafilm had an effect on larval growth and development.

In their study, the researchers found that both the larval growth rate and length change after 48 hours were significantly increased when the NGM agar plates were wrapped with parafilm. 

Researchers also found reduced variability in growth among parafilm-wrapped replicates in this study. This echoes findings of a previous study which looked at the effects of parafilm on the model plant, Arabidopsis thaliana. Overall, this suggests that parafilm helps to create a standardized condition for measuring responses in model organisms.

Any researcher that uses parafilm as common practice with their organism should be aware of these possible effects and take the time to identify if this practice of wrapping up has any influence on their results. And in addition, perhaps there are other types of common practices out there that can affect results...that we just don’t know about yet. 

I chased lemurs around Madagascar to help stave off their extinction

Planting fruiting trees is a vital component of reforestation and conservation efforts

Jake Krauss

Wildlife Conservation

Rice University

A lemur, a primate cousin that evolved separately on the island of Madagascar, leaps above me through the rainforest canopy. Ninety percent of the lemurs on this island off the east coast of Africa are in danger of extinction. I am studying the Milne Edward’s sifaka, an endangered species of lemur in Ranomafana National Park. I am following these lemurs around to better understand their diet and behavior, research which hasn't been updated in over a decade but is very important for this species' conservation.

I’m a senior student at Rice University collecting data for my honor’s thesis. I received a grant from my school to go to Madagascar to conduct this research. 

I run through the forest after the lemurs, taking observations of their behavior every three minutes, following the protocol for past studies. During my time here I am following six different groups of lemurs, three in degraded forests and three in pristine forests. The group I'm following today, which occupies the disturbed forest, consists of two adults females and two juveniles. They run out of sight down a steep ravine. One false step, and I slide down the muddy slope on my butt. Desperate for every piece of data, I pick myself up and keep running to maintain pace with the lemur I’m focused on. She’s a mother, and a green-eyed baby pokes her head out below mom's belly. She nibbles on some young leaves, a common food item in this degraded forest.

As compared to the pristine forest, there are less vines and more tall trees with fruits and seeds. So far, my observations mirror the finding of previous research that lemurs eat more fruits and seeds in degraded forests because these foods are relatively more available. This research shows the importance of having these food items available for the sifaka lemurs to eat and reinforces the approach taken by reforestation efforts elsewhere on the island: tree species that yield abundant seeds and fruits should be prioritized.

I will return to the US after my time with the lemurs and publish these results. Hopefully, this will aid conservation managers in informing reforestation efforts to provide food for the endangered Milne Edwards’s sifaka lemurs.

Hermit crabs are using old bottle caps and plastic as shells — and it's killing them slowly

Around 570,000 crabs become entrapped in debris each year on the Henderson and Cocos (Keeling) islands

Dori Grijseels

Neuroscience

University of Sussex

Unlike many other crustaceans, hermit crabs don’t have their own hard shell to protect them. Instead they find an empty shell, often left behind by a sea snail, to climb in. However, hermit crabs are not particular about their shell: in fact, an artist convinced hermit crabs to use 3D printed shelters in the shape of famous cities. 

Because of this, we might expect that hermit crabs are quick to adapt to increasing amounts of plastic on their beaches. Indeed, crabs have been found using old bottle caps and other plastic objects as shelters. But a new study by Jennifer Lavers from the University of Tasmania shows that this plastic is in fact incredibly damaging to hermit crab populations. 

The major danger for the crabs is plastic bottles that wash up on shore. If these bottles don’t have a cap or have a hole of some sort, the hermit crabs may climb in them. However, they often can’t climb out again and get stuck without food and water, causing them to die after about a week. 

note: Dori (lab note author) gave permission to use this

Hermit crabs as seen in Okinawa.

Dori Grijseels (2019)

This is the start of a chain reaction. Hermit crabs rely on their shells to survive, and good shells are hard to come by. If a crab dies, it releases a special odor that other crabs can detect. They will climb into the bottle in search of the shell of the dead crab, but get stuck themselves. This was probably the cause of the single bottle with 526 hermit crabs stuck in it that the researchers found. They estimated the total number of hermit crabs that got stuck in bottles on the Cocos (Keeling) Islands and Henderson Island was about 507,000 and 62,000 respectively. 

We often hear about the damage plastics cause in our oceans, but this research shows that the effects are not limited to marine environments. Many terrestrial animals are also endangered by the plastics that accumulate on beaches. If we don’t reduce the amount of plastics that end up in the ocean, we could risk extinction of these species.

Shi En Kim

Molecular Engineering and Materials Science

University of Chicago

You’ve probably heard of the Google Glass (and its demise), but there are more vision-based wearables in development, including smart contact lenses. Smart contact lenses are not yet available on the market, partly because they face additional technical challenges. Most people might overlook the inconvenience of wearing spectacles, but we probably won’t see eye-to-eye on the matter of placing an electronic device directly on our eyeballs. 

Recently, a group of South Korean researchers demonstrated that their latest smart contact lens design is indeed feasible, going as far as to demonstrate for the first time that their prototype can be worn safely by humans.

It seems so — it is made from hybrid nanomaterials encased in a soft, stretchable polymer. The lens can be elongated up to 1/3 more than its original dimensions, repeatedly too.

Is the lens safe? Check — it operates at low voltages and maintains a stable temperature far below body temperatures. 

Is it convenient to use? Why, yes — it can be wirelessly charged to full power in four minutes. The researchers claim that their smart contact lens are the first that can be operated continuously, thanks to a built-in supercapacitor. The supercapacitor stores a large amount of charge per unit volume and releases it, allowing for continuous function.

How is this contact lens “smart”? Well, it blinks. So far, its only function is for an embedded LED to turn on and off. 

Nevertheless, this research has cleared the major technical hurdles. Now, it behooves the rest of society to ask why we should want smart contact lenses. 

Previous attempts by major companies have had outlooks far from eye-catching. Google Contact Lens was conceived in 2014 for monitoring glucose levels in tears, but the project has been discontinued because of measurement inaccuracies. Samsung has filed several patents to develop smart contact lenses for augmented reality, but a concrete product remains nowhere near market-ready. If we blindly chase after the bandwagon, then smart contact lenses might suffer the same fate as the Google Glass

Here's how earthquakes rocked Puerto Rico into another emergency

Multiple events shook Puerto Rico's southern coast

Michele Cooke

Geosciences

University of Massachusetts Amherst

The moderate earthquake in Puerto Rico makes January 5th's 5.8 a foreshock (Ed: a tremor that occurs before a larger event, the mainshock). There have been several earthquakes over the past few days along the southern coast of Puerto Rico.

The map below is from the IRIS interactive view, showing earthquakes since Saturday with depth in color (purple = <33 km) and size denotes magnitude. The east circle represents the largest event, which is not quite co-located with the other events.

A map of seismic events around Puerto Rico that occurred in January 2020.

Michele Cooke

The focal mechanism shows normal slip event with some strike-slip (Ed: one kind of motion involved in an earthquake, where plates are moving horizontally relative to each other) and the expected seafloor displacement triggered a tsunami warning, which was cancelled.

Anthony Lomax

The following image from Wikipedia views Puerto Rico from the northeast showing the Puerto Rico trench to the north of the island and the less active Muertos Trough to the south of the PR.  The recent shallow normal-strike-slip slip seismicity is likely related to the deeper Muertos trough. Like other islands in the northern Caribbean, strain within Puerto Rico is partitioned with off-shore subduction zones and on-shore strike-slip systems.

Puerto Rico from the northeast showing the Puerto Rico trench to the north of the island and the less active Muertos Trough to the south of Puerto Rico.

You've probably seen the reports coming out of Puerto Rico of widespread damage from shaking. The soft first story of many buildings have collapsed. When you think "soft first story," think of vertical posts to support the house so you can park underneath. When the ground shakes, these posts are very unstable. 

We will likely learn of more damages and fatalities with time. I hope that the federal government acts quickly to support our fellow citizens in crisis in and not repeat mistakes made after Hurricane Maria.

Coral reef bacteria are being killed off by human activity

Microbes could provide important clues about the health of coral reefs

Janani Hariharan

Soil Science

Cornell University

Across the globe, coral reefs are in trouble. One of the biggest challenges we face today is figuring out how to save them. Like any good doctor, we need an efficient and reliable way to determine how sick or healthy different coral reefs are. A team of researchers from the USA, Mexico and Cuba wonder if reef microbial ecology might be the answer. 

Photo by Francesco Ungaro on Unsplash

To understand how the microbial community differs between different types of reefs, the team sampled water from different coral reefs on the coasts of Florida and Cuba. Jardines de la Reina in Cuba, a reef that has been largely protected from human activity, had the richest microbial community. This area was especially rich in bacteria that can perform photosynthesis and cycle nitrogen, thus increasing productivity in the region. 

In contrast, the site that had been most impacted by human activity, the Florida Keys, had a smaller and more variable microbial community. Disturbances like overfishing, coastal development and nutrient run-off in the Keys seem to have produced a small but competitive group of microbial residents. Studies like these can help us understand how human activity can disturb the microbial communities of coral reefs.

Previously used metrics like coral coverage and algal coverage did not vary significantly between these reef systems, indicating that these might not be the best metrics to measure coral reef health. Perhaps it's time to let the microbes speak and tell us the true story of coral reef health. 

Nanoparticles could one day store your vaccination record in your skin

Quantum dots successfully provide in-skin vaccination record (in rats)

Satarupa Bhaduri

Cell Biology

University of California, San Diego

Vaccines save 2-3 million lives around the world annually. However, 1.5 million deaths from vaccine-preventable diseases still occur each year. Although many factors may lead to undervaccination, one important factor is the inability to accurately determine whether an individual has previously received a given vaccine, especially in developing countries where many people may not have vaccination records

Several alternatives to the traditional paper records have been proposed, including smartphone-based databases, fingerprinting and communication chips. However, these expensive options have not yet become prevalent due to difficulty in implementation. 

In a recent study published in the journal Science Translational Medicine, a group of researchers, including scientists from MIT and the Chinese Academy of Sciences, has come up with a cheap and easy-to-implement solution. They have designed a system to administer and detect very small nanoscale particles called quantum dots. The quantum dots are administered along with the vaccine and remain in the skin, serving as a vaccination record. 

First, the researchers had to synthesize the quantum dots, which are very small crystals, in the range of 2-10 nanometers. These particles are widely used in biomedical imaging, photovoltaic cells, and some TV screen displays. Scientists selected one type of quantum dot (called S10C5H) for its structural and functional stability under simulated sunlight. The quantum dots were then encapsulated in micro-sized capsules made of a special polymer. These encapsulated particles wrapped in pigmented human skin showed stability upon exposure to simulated sunlight up to an equivalent time of 5 years. The encapsulated polymers were packed in microneedles that were designed to dissolve in the skin.

A pair of black and white rats

A pair of black and white rats

Jason Snyder on Wikimedia Commons

The researchers subsequently treated rats with these dissolvable microneedles containing the polio vaccine and quantum dots (as the record of vaccine administration). No significant unaccounted tissue damage or toxicity was observed in the rats. The quantum dots could be visualized only under special LED lights in the near-infrared region (like the waves emitted by remote control), so they are invisible to the naked eye. For imaging purposes, researchers designed special lenses and imaging software for a Google Nexus 5X smartphone. Scientists found that the record-keeping quantum dots remained visible under near-infrared light for at least nine months. Furthermore, the dots did not seem to negatively impact the effectiveness of the vaccine: animals had antibody levels that were considered high enough to protect them from the disease.

For effective usage in the real world, clinical studies assessing biocompatibility and potential toxicity of the encapsulated dots will have to be done on humans. Overall, this study opens new and exciting possibilities for medical data storage, which could prove very valuable in eliminating vaccine-preventable diseases. 

DNA barcodes help identify fish eggs and inform conservation

Determining where fish spawn could help us protect these crucial habitats and bolster declining fish populations

Makenzie Burrows

Marine Science

University of South Florida

Fish are economically and ecologically important in the Gulf of Mexico, yet their stocks are decreasing due to overfishing. One major way that we can help protect fish is to protect the habitats where they reproduce. But in order to do that, we first have to find out where they reproduce. One way to find these spawning habitats is by using floating fish eggs.

Nicole Seiden

Before setting up projects focused on reef fishes, like grouper and snapper, we needed to know if eggs from shallow water fishes stay in the shallows or if the eggs move into deeper waters as they float.

Fish eggs can be found in most surface waters, making them easy to collect with a plankton net. However, these eggs are usually clear balls the size of the tip of a pencil, making them difficult to visually identify down to species level. To solve this problem, we use a laboratory method called DNA barcoding. DNA barcoding allows us to look at the genetic material of each fish egg to figure out which species it belongs to. Each species has a unique DNA signature, just like how each product at a grocery store has its own unique barcode.

Using DNA barcoding, we found that most shallow water fish eggs stay in shallow waters. This information will help us plan future fish egg collections to help inform fisheries managers where and how much these shallow water species are spawning. 

Photons pop in and out of existence to transfer heat

It isn't heat conduction, convection, or radiation

Katherine McCormick

Quantum Physics

University of Washington

When we learn about heat transfer in school, we learn there are three types: conduction, convection, and radiation. But scientists have finally observed a fourth type of heat transfer, and it's all thanks to quantum mechanics.

One main principle of quantum mechanics is so-called zero-point energy, or vacuum fluctuations. This means that, even at a temperature of absolute zero, a system will still have some amount of energy. This causes all sorts of bizarre phenomena, like particles randomly popping in and out of existence near a black hole, or, in this case, photons popping in and out of existence between two plates of metal. Known as the Casimir effect, these short-lived, "virtual" photons can transfer energy from one of the metal plates to the other.

The scientists observed the effect in this new experiment by making the metal plates out of a deform-able material that can vibrate like the head of a drum. Each of these drumheads were tethered to blocks at different temperatures. Heat from the blocks caused the atoms in the plates to jiggle faster, making them vibrate. But because the blocks were at different temperatures, the two drumheads vibrated with different amounts of energy. When they were brought close enough together, the scientists saw that the Casimir photons took energy from the hotter drumhead and transported it across the vacuum to the cooler one, until the two were in thermal equilibrium. 

Overall, the influence of quantum mechanics on everyday human experiences like temperature is a hot research area, and I personally find it pretty cool!

Ice Bucket Challenge donations have helped fund promising ALS clinical trials, especially for "fast progressors"

There are currently only four drugs approved to help treat amyotrophic lateral sclerosis (ALS)

Monica Javidnia

Neuroscience

University of Rochester

Promising results from a Phase 2 clinical trial show AMX0035 (Amylyx Pharmaceuticals), a combination of sodium phenylbutyrate and tauroursodeoxycholic acid, may slow disease progression in individuals with amyotrophic lateral sclerosis (ALS). The news comes days after the passing of Pete Frates who championed the ‘Ice Bucket Challenge’, raising global awareness of the devastating disease and over $200 million for research and advocacy efforts. The trial, known as CENTAUR (Combination of Phenylbutyrate and Tauroursodeoxycholic Acid), was funded in part by Ice Bucket Challenge donations.

ALS affects approximately 16,000 people across the United States, and only four drugs are currently approved to help treat the disease. In ALS, a loss of nerve cells that control movement (motor neurons) leads to progressive muscle weakness. As the disease progresses, people with ALS experience difficulty with movement, speaking, eating, and breathing, and may require interventions such as a tracheostomy to prevent respiratory failure.

The CENTAUR clinical trial found that research participants taking AMX0035 had a significant reduction in disease progression compared to placebo, as measured by the ALS Functional Rating Scale. Notably, enrollment criteria for the study selected 'fast progressors' — a subtype of participants believed to be more likely to show an effect (if there is one) during a trial — by studying a database of over 10,000 people with ALS. In an interview with Neurology Live, study principal investigator Dr. Sabrina Paganoni stated, "These patients are not biologically different from other people with ALS; this was basically a statistical strategy to increase our power to see a treatment effect with a relatively smaller trial." Participants are being invited to enroll in an open-label extension study, providing everyone with access to the study drug and an extended follow-up period. 

Prior research studies have found that sodium phenylbutyrate improved outcomes in an ALS mouse model and provided neuroprotection, while tauroursodeoxycholic acid reduced endoplasmic reticulum stress and prevented neurotoxicity. Both tauroursodeoxycholic acid and sodium phenylbutyrate were each individually tested in people with ALS, but there was no larger-scale follow-up of the compounds until now. Amylyx Pharmaceuticals found the combination reduced cell death, prompting the current trials in ALS as well as Alzheimer’s disease.

Being exposed to reactive oxygen helps worms live longer lives

Worms exposed to reactive oxygen species early in life actually lived about 18% longer than their unexposed counterparts

Satarupa Bhaduri

Cell Biology

University of California, San Diego

The most widely accepted theory of ageing is that reactive atoms or molecules of oxygen, referred to collectively as reactive oxygen species (ROS), damage molecules like lipids, DNA and proteins. Accumulation of ROS has been implicated in many age-related diseases, including chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases, and cancer.   

In a recent study published in Nature, a team of scientists from the University of Michigan and the Chinese Academy of Sciences have discovered that roundworms (Caenorhabditis elegans) exposed to high levels of ROS in the early stages of their development are more resistant to oxidative damage, and this allows them to live longer. Roundworms are powerful biological model organisms as most of their genes have functional counterparts in humans. So, this could illuminate how to mediate the effects of aging in humans, as well.

The group studied two different groups of roundworms who experienced different ROS levels during early development, allowing them to categorize the worms as being in one of two states: oxidative (stressed) and reduced (normal). Both groups of worms went on to have similar ROS levels to each other in early adult stages. However, by late adulthood (day 7 in worms), they saw that the oxidized group had significantly lower ROS levels than the reduced group, and they were living about 18% longer. 

The researchers also looked at gene expression patterns in the two groups of worms to determine the molecular mechanism of the stress resistance. They found a major difference in the way that proteins called histones function. Histones package and order DNA. An enzyme called H3K4me3, which alters the chemical structure on the surface of the DNA, was found to be reduced in the worms that had been part of the oxidated group early on. This modification acted as a form of memory for the cells and led to increased stress resistance in later life. 

This study establishes how early-life events alters DNA expression throughout an organism's life and ultimately leads to stress resistance and increased lifespan. One next step is to look for evidence that similar mechanisms play a role in human aging. This important study might eventually lead to improved treatments for age related degenerative diseases.

Not surprisingly, science still has a huge racism and sexism problem

All STEM fields have this problem, with physics having particularly large gaps

Vanessa Vieites

Psychology

Florida International University

Stereotypes about others’ gender and race can influence the way we perceive and judge them. Such biases have been shown to affect employers’ hiring decisions, even when evaluating “fake” but identical resumes. A 2019 study examines how intersecting stereotypes about gender and race influence professors’ perceptions of fictitious post-doctoral candidates applying for positions in different STEM departments at universities. 

In science, as the study shows, there is still a tendency to view women as less competent and hireable than comparable men, but fields that are more male-dominated (i.e., physics) appear to be more discriminating than those that are more gender-balanced (i.e., biology). Meanwhile, Black and Latinx PhDs, especially those who are women, tend to be viewed as less competent or hireable than comparable White and Asian PhDs. 

We’ve known there to be racism and sexism in the academy for a long time, but what is unique about this study is that the authors took an intersectional approach to their analyses. For instance, instead of just looking at the effects of race (i.e., black vs white applicants) or gender (i.e., men vs women) on professors’ ratings of applicants’ hireability, likability, and competence, the authors made sure to analyze the effects of intersecting identities (i.e., Black/Latinx/Asian women, Black/Latinx/Asian men in comparison to white men/women) on such outcomes. Their results highlight how understanding the underrepresentation of women and racial minorities in STEM requires examining how racial and gender biases intersect.

What I found most interesting about the study’s findings is that even though physics and biology are both STEM fields, the discrimination against women was found more so in physics, where women are severely underrepresented compared to biology (Women earn a little more than half of doctorate degrees in biology but only one-fifth of the doctorate degrees in physics). Similarly, the study also found that Asian applicants were not discriminated against compared to black and Latinx candidates, which further supports the point about representation in STEM fields making a difference in how job candidates of different groups are perceived and rated for those jobs.

These findings raise some important questions and implications about gender and racial discrimination in STEM. Would women be more accepted in currently male-dominated professions if those professions were more gender-balanced? Do women and some racial minorities appear "out of place" in physics because they are underrepresented in that field as it stands, thus leading to hiring biases? Are women relatively accepted in the life sciences because such fields have become more “feminized” over the years and, thus, are perceived as “easier” to excel at? 

We need better volcano forecasts to prevent tragedies like New Zealand's Whakaari explosion

Researchers are working on modeling eruptions to prevent loss of life when volcanoes explode

Two weeks ago, Te Puia O Whakaari Island, off the coast of Aotearoa (New Zealand), erupted, killing at least 16 people. The volcanic alert level for the island was raised to Level 2 in November, suggesting the volcano may be entering a state of increased volcanic activity. But what does a Level 2 mean? And is it even possible to forecast when a volcano can erupt?

Raising the volcano to a Level 2 indicates changes in volcanic parameters (like seismic activity). Levels 1 and 2 relate to volcanic unrest, while levels 3-5 indicate current eruptions. GeoNet, a hazard monitoring program of Aotearoa, indicates that eruptions can occur at any level on the scale, and sometimes no eruptions occur even after alert levels are raised. After the island was raised to a Level 2, an eruption likelihood was calculated on December 2nd, estimating an 8 to 14% chance of an eruption in the following 4 week period. The eruption occurred 7 days later on December 9th.

Photo by Farrah Fuerst on Unsplash

A sub-discipline of volcanology research is centered around improving forecasts of when volcanic eruptions may occur. While strides are being made in this area of research, not all volcanic eruptions are the same, and some are harder to forecast than others. Monitoring around active volcanoes is used to forecast if an eruption is possible in the near future. Parameters such as seismic activity, flow of electrical current through rock, deformation of the ground around the volcano, and changes in the gas emitted from volcanoes (such as an increase in sulfur dioxide) may all be a precursors to an eruption and are often part of a monitoring program. However, changes in these parameters may occur without an eruption, and sometimes eruptions may even occur without any notable changes in those parameters.

The Whakaari eruption was a steam-based eruption, among the hardest to monitor. Shane Cronin, a Professor at the University of Auckland, explains that in these types of systems, water is trapped in rock pores, and any changes in the system may cause a sudden expansion of the water into steam, leading to catastrophic eruptions.

The likelihood of continued eruptions of Whakaari are steadily decreasing, but these events beg the question of what can be done to assure safety of those who live near and travel to active and dormant volcanoes. Massey University volcanologist Associate Professor Gert Lube and others were recently awarded a million New Zealand dollar grant to test volcanic eruptions and flows, similar to those that occurred in Whakaari, using computer simulations. They hope their research will help more effectively assess risks associated with volcanoes like Whakaari.

Could radiation in deep space fry astronauts' brains?

New research in mice suggests that long-term low-dose radiation impairs learning and memory

Thiago Arzua

Neuroscience

Medical College of Wisconsin

Even though it happened half a century ago, the Moon landing remains one of the most ambitious space exploration projects ever. The future, however, holds even more exciting and longer flights. It takes about a week to get to the moon and back, depending on the route. But the much-talked-about trip to Mars would take us, at a minimum, 8 months — one way. During those months, aspiring interplanetary settlers would be exposed to a constant dose of radiation, without the protection usually afforded by Earth’s magnetic field. 

We are still unsure about the impact that this radiation exposure could have on  astronauts’ bodies. New research done by a group led by Charles Limoli, a radiation oncologist at the University of California, Irvine, suggests that chronic, low dose radiation can lead to severe impairments in learning and memory, as well as distress behaviors — at least in mice.

In this study, the scientists exposed mice to radiation at a rate of 1 milligray per day for 6 months — a relatively low dose that is comparable to what a deep-space astronaut would encounter. After this exposure, the scientists examined the hippocampus of the mice, the area of the brain responsible for the formation of memories. There they found differences in the electrical activity between the exposed mice and the control group. Exposed mice also had reduced synaptic plasticity — the ability for neurons to make new connections, which is an important component of learning.  Scientists also  conducted tests to measure both cognition and anxiety. These tests showed that the mice exposed to radiation performed worse in learning and memory tests and displayed increased anxiety-like behaviors.

Mars shot from the Curiosity Rover

NASA Goddard Space Flight Center via Flickr

So what does this mean for future Mars missions?

In the original paper, researchers write that this “radiation environment in space will not deter our efforts to travel to Mars.” This is exactly the type of research needed if we are serious about a settlement on the red planet. While we do not have immediate answers to the radiation problem, understanding how it affects brain function is a start. In space travel, and in science in general, there are known unknowns and unknown unknowns. The more unknowns we are able to study here on Earth, the better the chances of humans setting foot on another planet in the foreseeable future.

Good news: Canadian Arctic seals have not been eating plastics

Publishing null results helps us understand where wildlife is safe from plastic ingestion

Farah Qaiser

Molecular Genetics

University of Toronto

Plastics are everywhere. It isn't just humans who are ingesting microplastics on a daily basis, but animals too, such as sea turtles and albatrosses. Plastics can even be found in remote locations, including a high-altitude lake in the Pyrenees mountains in southern France. This increase in plastic pollution prompted researchers to ask: how prevalent is marine plastic pollution, and to what extent is it impacting Arctic wildlife?

But there's good news here for once: a new study out in the Marine Pollution Bulletin found no sign of plastics in the stomachs of 142 seals found in the eastern Canadian Arctic.

Madelaine Bourdages

Seals are an important member of the Arctic marine ecosystem, and act as a vital source of nutrition, cultural and economic value in northern communities. Any plastic ingestion would impact not only the seals, but their surrounding ecosystem and communities too. To investigate whether seals were ingesting and accumulating plastics, researchers collaborated with Inuit hunters to examine the stomach contents of 142 seals found in Arviat, Naujaat, Sanikiluaq, and Iqaluit between 2007 and 2019. 

Together, the Inuit hunters and researchers characterized the seals; they  determined age, examined tissue pathology, and used sieves to collect plastics >425 μm in size (that's about the size of the period at the end of this sentence!) in the stomach contents for 135 ringed seals (Phoca hispida), six bearded seals (Erignathus barbatus) and one harbour seal (Phoca vitulina).

The study found no accumulation of large plastics in the seals examined. Instead, krill or small fish were found in the seal stomachs, with a few containing parasitic roundworms. Around 30 seal stomachs were empty (consistent with other studies), and for 10 stomachs, the contents could not be identified as they were partially digested.

Seal stomach contents.

Madelaine Bourdages

It's worth noting that there may have been microplastics smaller than 425 μm in the seal stomachs. These microplastics wouldn't have been picked up by the sieves, but they also are likely too small to be retained and would have passed straight through the seals' stomachs.

The lead author, Madelaine Bourdages, is a graduate student at Carleton University. Bourdages commented that the results were somewhat surprising given the increase in plastic pollution in the environment, but points out that since “the majority of the seal stomachs contained euphausiids [krill] and fish, [this] suggests that the seals we looked at were likely feeding somewhere in the middle of the water column, and could have potentially been less exposed to larger plastics that typically either float or sink.”

Interestingly, this study is one of the few to report zero plastic ingestion; others include no plastic ingestion found in 134 silver hakes (Merluccius bilinearis) on the Newfoundland south coast, and in Antarctic fur seal scat and albatross stomachs from three islands in the Indian and South Atlantic Oceans. Reporting null results like this study is important — not only to establish a baseline to monitor marine plastic pollution in this particular region, but to better understand where plastic ingestion is and isn't happening.

Instead of climbing into an MRI machine, a new test asks children to just blink

We can now bypass MRIs and instead use trace eyeblink conditioning to measure brain function

Vanessa Vieites

Psychology

Florida International University

The hippocampus is a region in the brain where memories about the space around us and how to navigate it, as well as memories about events that affect our lives are formed. But testing the relationship between the brain and behavior in young children has been challenging in the past, which is why we need novel methods.

Measuring brain function in young children is often challenging because the tools we normally use can intimidate children. For example, a young child may feel scared or restless in an MRI machine, resulting in either unusable data or causing the child to drop out of the study.

That's why in a study out earlier this year, my fellow researchers and I used trace eyeblink conditioning (EBC) — a novel way to indirectly measure the hippocampal function — to assess spatial and episodic memory abilities in children between the ages of three and six. Because EBC is safe and non-invasive, it is an ideal way to examine learning, memory, and brain function in children.

The trace eyeblink conditioning (EBC) method in action.

Vanessa Vieites

In EBC, children are presented with a series of auditory (i.e., tones) and tactile (i.e. airpuffs to their eye) stimuli. What makes EBC rely on the hippocampus is that the tones and airpuffs are separated in time by 500 milliseconds, and that time lapse, while seemingly insignificant, can be difficult for preschool children to remember. Those who develop a learning response will blink at the sound of the tone alone, thinking that the airpuff will follow shortly.

In our study, we also asked children to take three additional tests. One was a spatial reorientation test, in which they searched for a hidden object in a rectangular room with 3 white walls and one red wall. The second was an episodic memory test, in which they memorized sequences of pictures. Lastly, children completed a processing speed test, which does not rely on the hippocampus.

Children who were better at detecting the predictive nature of the tone were also better at using the geometry of a room to locate a hidden object, regardless of age. These findings suggest that hippocampal function underlies the use of, specifically, geometric strategies for navigating, even in young children.

Teresa Ambrosio

Chemistry

University of Nottingham

Using carbon dioxide, a chemical waste, as starting material for chemical transformations has been often proposed as a way to design green chemical reactions. But one problem is that carbon dioxide is a highly stable chemical, which means that its chemical conversion into other products requires harsh treatments, such as the use of high temperature and pressure.

Metal photocatalysis, which is a combination of using light and  metals to speed up chemical reactions, could be a solution to address the problem. Ideally, the photocatalyst, a chemical system that absorbs light as a source of energy to initiate a chemical reaction, should be non-toxic, cheap and widely available for this promising technology to find industrial applications. A compound called copper (I) oxide, also called cuprous oxide, seems to be the best fit as it meets current chemical and industrial requirements.

Using carbon dioxide as the basis for chemical reactions, hopefully, will cut down on the amount of this happening around the world

 Photo by Diana Parkhouse on Unsplash 

However, cuprous oxide can easily undergo other undesired reactions with oxygen atoms and is unstable in water. This is the major drawback for any suitable implementation of metal photocatalysis technology.

Engineers at Nankai University in China, in collaboration with  researchers at the University of Toronto in Canada, have now solved this challenge. They used copper nanocubes to convert carbon dioxide into carbon monoxide. The formation of those  nanocubes is a relatively simple process, and allowed the team to study the properties of this new material by shining visible light with an intensity 40 times that of the radiation of the sun onto the copper nanocubes. As a result, carbon dioxide (in the presence of hydrogen gas) was successfully transformed into a mixture of CO and water.

This study is a step toward making chemistry and industry more sustainable - and these days, every step toward building a greener world counts. 

Questions about biology, sex, and gender? We have answers

Biological essentialism is not based in fact

Gabriela Serrato Marks

Marine Geology

Massachusetts Institute of Technology

Sex and gender identity have been in the news,  so you, like J.K. Rowling, might be wondering about the difference between sex and gender, or if sex is "real."

First of all, here's a vocabulary review so that we're all on the same page.

Gender identity is our internal sense of who we are (example: woman). It's different from gender expression, which is our external presentation (example: femme). Both of those are different from sex, which refers to our chromosomes, hormones, and genitalia (example: female). With me so far?

Now, sometimes, when people discuss sex and gender, they look to scientific research on these topics. They might end up touting biological essentialism, or the idea that there are two binary sexes (male and female) which ties people to a binary gender identity (man or woman). There's a very fine line, or no line at all, between biological essentialism and transphobia. Biological essentialism is particularly harmful because it makes it seem like there is basis to ignore the existence of intersex or non-binary people, when that's really not the case.

The science is abundantly clear: sex isn't binary. If you want to learn about this in-depth, we have a whole article on it.

But more importantly,  scientific research should be irrelevant when it comes to treating people with respect. 

In fact, research into the genetic or medical component of stigmatized identities might serve to further biases against marginalized people.

So, before you turn to science to defend transphobia, it's time to re-evaluate your biases. 

Reindeers thrive on the Svalbard islands after a century of conservation

Svalbard reindeer were almost hunted to extinction

Hannah Thomasy

Neuroscience

University of Washington

Svalbard – an archipelago halfway between continental Norway and the North Pole – was discovered in 1596. This discovery proved devastating for the group of islands' wildlife as Svalbard reindeer were hunted extensively and were extirpated from much of the archipelago. 

In 1925, the Svalbard reindeer was declared a protected species. Over the course of four summers, Norwegian researchers surveyed this remote archipelago to determine the effects of nearly a century of protection.

What they found was encouraging: the Svalbard reindeer population had reached nearly 22,500 animals, the highest ever recorded and 13 times more than the estimated population in the 1950s. 

Researchers also collected and radiocarbon-dated ancient reindeer bones from all over the archipelago. Using the age of the bones and the location in which they had been found, researchers were able to estimate the area occupied by reindeer prior to the arrival of humans on Svalbard. Today, Svalbard reindeer have re-colonized all of their historical territory. 

While this is good news for this subpopulation of reindeer, researchers point out that in many other areas of the world, reindeer have not been as lucky. Dramatic declines have been reported in several Canadian provinces (likely related to commercial forestry) and poaching continues to be a major problem in Russia.

In 2019, Massive Science covered some ground. We wrote about climate change killing off biodiversity, galaxies eating one another, parakeet mate selection, and on and on. We polled the Massive staff for their favorite stories of the year, both in what we worked on and in the outside world. But first, our top five most popular articles of the year:

#5

After another devastating intergovernmental report on wildlife loss, Cassie Freund wrote this urgent call for action. It's the very real end of the world, why isn't anyone acting?

#4

Neuroscience is Massive's bread-and-butter, so Claudia Lopez-Lloreda's story on fish giving up and the brain cells responsible checked a lot of boxes. Next time you quit on something, you'll know who's at fault.


#3

"Unexpected science" is another angle our writers have gotten serious mileage out of, and Darcy Shapiro's article on gorilla teeth, snacks, and how that changes human history is a classic of the genre.

#2

Definitely another "unexpected science" entry, Molly Sargen's story combined math, bridge building, and breakfast food. Now we know our audience likes that and more breakfast food science will be coming in 2020. 

#1

It's got it all: space and a vague sex angle. What more could you want? You might say that Mackenzie Thornbury's article went viral. We won't though. 

Sometimes though, what we think is cool and what you all think is cool doesn't match up. We're not mad about though, we know disagreement is natural. Not mad at all. Here are our personal faves that we think you should give a second shot. No pressure though! 

Or, as it was more affectionately known in the Slack channel: Babies...in...SPAAAAAAACE.

Another Cassie Freund work on the actual human effort to get around conservation efforts that other humans are employing to save the planet.

"Connecting brains" is a sub-genre of our normal neuroscience work and Jordan Harrod wrote one of the best ones we've ever seen. 

Yeah, the science is cool, the writing is great, but you know what really spiced up Luyi Cheng's debut article? The gifs

We love all Our Science Heroes equally, but there's something about du Châtelet. If a man had had her adventurous, influential life that included standing on Newton's shoulders and having Voltaire as a kept man, there'd be movies made about that man's life. This is our pitch for a du Châtelet biopic. Hollywood, please call us.

How 14 months in Antarctica changes your brain

Studying the effects of isolated, monotonous environments on the human brain has important implications for space travel

Claudia Lopez-Lloreda

Neuroscience

University of Pennsylvania

In a short correspondence published in the New England Journal of Medicine, neuroscientists studied the brains of polar researchers. The nine scientists lived in Antarctica for a span of 14 long months, enduring isolation and extreme environmental conditions. The neuroscientists used magnetic resonance imaging (MRI) to take pictures of the explorers’ brains and measure the volume of different areas before, during and after the expedition. When they compared the before and after scans, they found that certain brains areas became smaller in the explorers subjected to these extreme conditions compared to controls. 

Photo by NOAA on Unsplash

Of particular interest was the hippocampus, an important area for learning and memory. They found that a specific area of the hippocampus called the dentate gyrus seemed to be especially vulnerable to the Antarctic environment, with the most substantial decrease. The polar researchers also had lower levels of brain-derived neurotrophic factor — a protein that is important for neurogenesis — and worse performance on tests of spatial abilities. The authors say that these data should be taken with a grain of salt since only nine explorers were studied and it's unclear exactly which of the elements of the Antarctic mission contributed to these changes in brain structure and function.  Was it being limited to interacting with the same small group of people for more than a year? Or living in a monotonous environment? Or stress? Or poor sleep? These questions can only be answered with more research.

Celebrating the Periodic Table of Elements

A chance to look back on accomplishments but also consider our planet's future.

The first recognized periodic table of elements was published 150 years ago by Dmitri Mendeleev and has been heralded as one of the most important scientific achievements in chemistry. It is also important in biology, physics, medicine and earth sciences; it is a universal language connecting students, teachers and researchers from all over the world. 

That is why the United Nations General Assembly and the United Nations Educational, Scientific and Cultural Organization (UNESCO) proclaimed 2019 the International Year of the Periodic Table of Chemical Elements (IYPT2019), holding conferences and symposiums in different countries and a closing ceremony in Tokyo. This is an opportunity to celebrate scientific achievements as well as the elements themselves — the Nobelium contest asked people to submit educational videos, stories, poems, songs, and art about the periodic table or individual elements. 

But it is also a chance to consider the availability of resources needed by a growing global population. 

cartoon periodic table

European Chemical Society

To highlight this, the European Chemical Society (EuChemS) designed a quantitative periodic table in which the area of each element is proportional to its abundance (in a logarithmic scale) in earth’s crust and atmosphere which is color-coded to represent how long each element will last if we continue to use it at the current rate. Some elements are of more concern than others because they are naturally less abundant in earth’s crust or they come from conflict minerals or they are not easy to recycle. Elements’ supply is especially threatened by their intensive use in devices like laptops, tablets, and smartphones. Examples of elements of concern include indium, which is part of the transparent indium tin oxide (ITO) layer of touch screens and tantalum, present in microcapacitors and which can come from the conflict mineral coltan. Both indium and tantalum have a recycling rate of less than 1% and considering the huge number of smartphones (it's estimated that there are nearly 3 billion smartphone users worldwide) - significant quantities of these elements are being lost.

Celebrating the periodic table has therefore become a call to preserve our earth’s precious resources and to live in a more sustainable way, by reducing the amount that we consume, repairing, reusing and properly recycling: this is how we can continue to enjoy our wonderful planet for generations to come.

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