New Mechanism of Regulating Gene Expression Discovered

A few months ago, much ado was made about results from the ENCODE project on the human genome, publicized as having made the discovery that 80% of the human genome has a biochemical function. While this is true (with ‘biochemical function’ being defined loosely and broadly), we don’t yet know how or why most of the long stretch of DNA in our cells is important. ‘Genes’ as we know them make up less than 2% of the total DNA. What purpose does the rest of it serve?

What Purpose does “Junk DNA” Serve?

The ENCODE project suggested that the rest of the genome had a strong regulatory potential. How do our cells control when to turn on certain genes, when to ramp up production of one protein and when to slow down? A lot of these regulatory mechanisms remain unknown. A team of researchers at Wistar Institute have now discovered one additional mechanism of regulation.

Before we move on, let’s briefly review how genes function. ‘Genes’ are essentially regions of the genome which are processed into intermediate molecules called ‘RNA’, also linear strings. These RNA strings are further processed to yield the protein that performs the gene’s function. Think of the gene as a ‘recipe’ for a protein, with the RNA molecule being the unfinished product halfway along the recipe. There are, however, some regions of the genome which are processed to form RNAs, but do not form proteins. They often have regulatory functions.

ncRNA-a (the region of the genome on upper segment of the loop) helps the mediator protein complex to gain a foothold on the right region, so that the gene (shown by ‘mRNA’ on the lower segment of the loop) can be transcribed. [Image Credit: Nature Publishing Group]

Long Non-Coding RNAs Regulate Gene Expression

Moving back to the research team, they had previously discovered that a class of these ‘non-coding RNAs’, which they have termed ‘ncRNA-a’, serve to activate processing of their neighbouring genes. But how do they do this? There are certain proteins called mediators which facilitate the processing of genes to RNA. They have now discovered that ncRNA-a helps these mediator proteins bind to these genes at the right place. To determine this, the team removed proteins known to be involved in gene processing (called transcription) one by one, and looked for changes in ncRNA-a mediated activation. And voilà, components of the mediator complex came up immediately. They also found that the chromosome forms a loop between the ncRNA-a locus and the gene locus, for the mediator complex to be able to gain a stronghold at the gene locus using the ncRNA-a as a base.

Why is this result important? It gives us a better idea of the factors controlling gene expression. And as importantly, it helps us understand our DNA just a little better. You can read about this research here.

How Does Our Brain Create Fear?

Why do we feel fear? For years, a part of the brain called the amygdala has been implicated in this emotional response. This region links memories with emotional responses, one of which might be fear. A patient (known as S.M.) with dysfunctional amygdalae on both sides of her brain has been known to show no fear in response to various fear-inducing stimuli, including life-threatening traumatic events.

Everyday Gas Induces Fear in the Brain

Another stimulus that is known to evoke fear is carbon dioxide. Inhaling this gas turns on a protein which in turn plays a role in fear and anxiety (how this protein works in inducing fear remains unknown). How would patients with damaged amygdalae react to this stimulus? A team of researchers at the University of Iowa tried to find out.

fear center in the brain
The first image is a scan from a normal patient and the next three are from patients with damaged amgydalae. The area marked in red shows the lesions present in their brains. [Image Source: Iowa Neurological Patient Registry at the University of Iowa]

‘Fearless’ Patients Show Fear

To their surprise, they found that the 3 people with lesion in their amygdalae (let’s call them patients) showed a greater degree of panic than a group of patients with normal amygdalae. The patients described having experienced emotions they had never felt before, with their descriptions residing well under the category of ‘fear’. Clearly, these results show that the amygdala is not an absolute necessity for fear. However, anticipatory responses to the inhalation, such as an increased heart rate before inhalation, were shown to be significantly increased in controls when compared to patients.

These results led the authors to believe that the carbon dioxide activated a previously unused pathway in patients with damaged amygdalae. One possibility is that most stimuli that normally induce fear are external—perceived visually or auditorily—, whereas inhalation of carbon dioxide represents a physiological, internal, change that does not need processing by the amygdala to generate fear. Another conclusion that the authors came to was that the amygdala might, to some degree, inhibit fear, since the degree of panic attacks was milder in the control group.

Fear is an important survival mechanism, and this experiment gives important clues to its origin. You can read about this research here.

Novel Method To Invade Cells

One of the current paradigms of molecular biology research is to study cells by manipulating them. Insert a piece of DNA and see what changes. Add a protein and see if the cell can now become cancerous. Inactivate a protein and see if a diseased cell becomes normal.

One of the trickiest steps in such processes is often getting the foreign substance inside a cell. Living cells have membranes designed to keep out foreign substances and to absorb just what the cell wants. How do we let particularly large molecules in?

Infiltrating the Cell’s Walls

Pieces of DNA are usually inserted into a longer fragment of DNA called a vector (to keep the DNA stable). The cell is then shocked to jolt the proteins in its membrane and make it temporarily porous. This method can work for small molecules, and another method is the chemical disruption of the membrane temporarily. The problem with these methods is that they change some properties of the cell, and the goal of such experiments is to observe changes in the cell that is ONLY because of the inserted molecule, and not due to other factors (such that the result of a shock might lead to). Another method is to deliver the molecule inside nanoparticles which can then enter the cell, but the nanoparticle is often captured by an organelle of the cell, and the molecule is then not released. The cell’s membrane also allows certain protein to pass through it—think of it like a gatekeeper, letting proteins of certain charges and small enough sizes go through while keeping out the others.

This image gives the workflow of the microfluidics device. Figure A shows cells flowing through a tube with a constriction. After being squeezed, these cells are now have the delivery material inside them. [Image Credit: Sharei et al; PNAS]

Squeezing Cells to Make Them Yield

A general method of insertion would thus be a useful tool in research. Researchers at MIT have come up with the solution mothers use when their children don’t eat food—they press in the child’s cheeks till their mouths open. This team has developed a microfluidics device that does something similar. Cells (and the delivery material) flow through a tubes under external pressure and are forced to pass through a tiny constriction in the tube (see figure). During this phase, the cells are compressed to such tiny sizes that their membranes ‘split’ temporarily, leaving gaps for molecules to enter.

The team used this method to generate stem cells (by inserting the necessary factors into cells) and found that this method had an efficiency 10 to 100 times greater than other existing methods. Their next step is to use this for therapeutic purposes, wherein a patient’s cells could be taken out of his body, injected with the necessary DNA/protein, and re-injected into his/her body.

You can read about this research here.

Deadly Ebola Strain Could Infect Asian Bats

Ebola is a viral disease that has been a threat for more than a decade. Detected in Africa, this virus causes a serious haemorrhagic fever and has high fatality rates. There have been indications that it is from bats that these viruses infect humans, and a new study in Bangladesh lends this further credence.

Source of the Disease

Diseases like Ebola emerge periodically in human populations, and just as suddenly, disappear following an outbreak. This patterns owes itself to the virus being ‘zoonotic’—a virus that infects humans via another organism. Zoonotic diseases are hard to eradicate because we can’t immunize animals in the wild. This is why we have effective vaccines for Measles (not zoonotic), but Ebola or the flu is always on the radar for health officials. Thus, a crucial step in studying zoonotic diseases is determining their primary hosts. One criterion for primary hosts is that the virus shouldn’t be too harmful to them. If it were, it would kill the host organism and would not be able to circulate for long periods of time, as it does. Humans are definitely not its primary hosts—each outbreak subsides soon after its origin because it is so lethal.

This innocuous virion is the cause of a deadly disease. [Image Source: wikipedia]

Ebola Virus in Bats

The organism which is the original reservoir of Ebola virus has not been known for certain, though previous studies have found a few species of bats infected with Ebola. Now, researchers have studied 276 bats in three regions of Bangladesh and identified antibodies against the Ebola virus in 4% of these, meaning that the bats have, at some point, been exposed to the Ebola virus. However, they haven’t found live virus in bats, which is the piece of evidence necessary to confirm that bats are a reservoir, i.e. a permanent ‘store’ of the virus.

What Does this Study Tell Us?

Bats harbouring antibodies for Ebola has already been found—what new information does this study yield? This study tested bats for 2 strains of the virus: the Reston strain which has been seen in animals across the world (and has not caused human disease), and the more deadly Zaire strain, which has a whopping mortality rate of around 80% and was previously seen only in Africa. Antibodies for both these strains were found by this study, which means that a Zaire Ebola infectious outbreak in Asia remains a distinct possibility. How possible? We don’t know, until we have more evidence on prevalence of the virus in its primary hosts.

This research was conducted by the EcoHealth Alliance. You can read about this study here.

Ancient Link Between India and Australia

The study of the human genome continues to yield new insights about our history. A new study on the variation seen across human populations has revealed an ancient migration from India to Australia 141 generations ago, one that hadn’t been on record.

It is accepted that human populations migrated out of Africa and subsequently colonized the world. Some previous studies have shown that a wave of migration (called the ‘southern route’ of migration) to the Australian landmass occurred around 45000 years ago, following which this population remained isolated until colonization by Europeans in the 18th Century. This study upends this conclusion.

How Does Such Genetic Analysis Work?

Before the era of airplanes and global migration, populations across the world were relatively isolated, mainly because of geographical barriers, and often because of cultural and social barriers. Thus, members of each population would only breed with other members of the same population. Over time, this lack of interbreeding, or genetic mixing between different populations, led to distinct patterns that could be seen in each population. It is by looking at similarities and differences in these that we can compare genetic data.

A Study of Global Populations

The distribution of samples used in the study. [Image Source: PNAS: doi: 10.1073/pnas.1211927110]

Researchers at the Max Planck Institute for Evolutionary Anthropology collected ‘genotype data’—genetic data only at commonly varying locations in the genome—from different populations across the world (see figure above), and looked for patterns of similarities across these populations in terms of their genetic data. Using this genetic data and known rates of genetic change, they found a genetic link between populations from Australia, New Guinea and Mamanwa (an ancient group from the Philippines). This is consistent with the ‘southern route’ theory. What was novel was a significant similarity between Indian populations and Australian populations. This indicates a pattern of gene flow from India to Australia approximately 4230 years ago, a period called the Holocene.

Genetic Link Matches Archaeological Record—Coincidence?

This is fascinating because of an archaeological factoid of this period. This represents the period when changes in tool technology, food processing and a dog native to Australia called the dingo emerged on the Australian subcontinent. Could this emergence be related to the migration occurring in the same period?

It is plausible that this wave of migration was not direct, i.e., it could have been through the region of S.E. Asia, which shares long cultural links with Australia. However, the patterns of similarity seen between the Indian and Australian populations are not seen in the South-East Asian populations which were also included in this study. This means that there was a direct migration between India and Australia.

The study of our past is a fascinating one. Genetic data is an invaluable tool in this pursuit, and provides a tangible way for mankind to trace its evolutionary past.

You can read about this research here.

Possibly the Largest Black Hole Discovered

Astronomers led by Remco van den Bosch, from the Max-Planck Institute in Heidelberg, Germany have discovered a massive black hole at the center of a galaxy 250 million light-years away. The black hole has a mass equivalent to 17 billion of our sun. It is quite possibly the largest black hole ever discovered and is turning galaxy evolution models on their side.

ngc 1277
Image credit: NASA / ESA / Andrew C. Fabian / Remco C. E. van den Bosch (MPIA)

Picture above, you can see the disk shape galaxy NGC 1277 that was captured by the Hubble Space Telescope. At the center of this galaxy is the black hole that scientists are saying accounts for 14% of the galaxy’s weight. To put the size of this black hole in perspective, our own milky way galaxy has a black hole equivalent to the mass of 4 million suns. NGC 1277 has the mass of 17 billion suns!

It has typically been thought that the mass of a galaxies black hole correlates to the mass of the stars in a galaxy. After this discovery however, it seems that theory may not be true. The ratio of this black hole to the mass of the stars in its galaxy are way off the typical charts. Small disk shaped galaxies typically have much smaller black holes that usually account for less than 1% of their mass. Finding one that accounts for 14% of its mass is truly rare. Black holes of this size are usually found elliptical galaxies.

It appears after further examination that this phenomenon isn’t as rare as once thought. Other black holes with similar characteristics have been found since NGC 1277 was discovered to contain a super massive black hole. According to a Space.com article, Remco van den Bosch is quoted as saying, “You always expect to find one sort [of a phenomenon], but now we have six of them,” van den Bosch said. “We didn’t expect them, because we do expect the black holes and the galaxies to influence each other.” It appears now scientists will have to determine if this phenomenon only exists in the early universe and how this information affects our theories of galaxy evolution.

For more information, visit the journal Nature.

The Deodorant You Eat???

You can file this away in your “I’ve Seen It All” file. It appears you can now have your candy and come out smelling like a rose all at the same time. No I am not kidding. The product is called “Deo” and it claims, ” Science and nature have come together to make a functional food that leaves your skin with a beautiful rose fragrance.”

Deo Edible Deodorant

So is it perfume candy, or is it a health and beauty product? To be honest, I am not sure where this product will wind up if it ever hits the aisles of a major box store. Beneo Group announced this new innovation on its website. Beneo seeks innovative solutions that “cater to the growing health awareness among their customers”. The ingredient manufacturer developed a relationship with a Bulgarian company, Alpi. Together they are marketing this “rose-scented boiled sweet” which they claim not only tastes sweet, but will “transmit an attractive rose fragrance through the skin”.

The active ingredient is a natural anti-oxidant called geraniol. Geraniol is a colorless liquid found in plants like roses, lavender and vanilla. They call this product a nutri-cosmetic because it leaves the body through the pores of the skin which in turn, leaves behind a sweet rose smell. According to their website, http://perfumecandy.com, four pieces of the candy are considered a serving. A serving size will be most effective for people up to 145 pounds. Wim Dries, Area Sales Manager for Beneo said, “Many people like garlic, and it’s especially popular in European diets, but the tell-tale smell lingers for some time after a meal. Deo is the perfect antidote.”

Deo has already sold out on Amazon.com and they are working to replenish their stock. To keep up with new developments, visit their website at http://perfumecandy.com or visit their Facebook page.

Alligators and Crocodiles Have Acute Sense of Touch

When you hear the word alligator or crocodile, the last thing to come to your mind is sensitivity. However, a Vanderbilt University study shows that alligators and crocodiles’ sense of touch is vastly more sensitive than ours. Their study is published in the journal Journal of Experimental Biology.

Baby Gator
Baby alligator in an aquarium. (Michael Todd/Vanderbilt University)

It is easy to look at an alligator and think that their tough skin would be nearly impervious to touch. In fact, their skin is more like armor than anything. Amazingly, they possess these pigmented spots that look like tiny domes all over their skin. These spots are called integumentary sensor organs (ISO’s). For years, these spots were a mystery. Many believed that these spots produced some sort of oil to help protect the skin. Others believed that they were sensitive to electromagnetic pulses, or possibly were sensitive to changes in water’s salinity. A 2002 study at the University of Maryland however, showed that these spots were sensitive to ripples made by water drops. This intrigued Ken Catania, Stevenson Professor of Biological Sciences at Vanderbilt, enough that he began studying the function of these ISO’s even further. Below, you can see a Vanderbilt University video featuring Duncan Leitch, a graduate student serving under Catania.

[Video Link]

 

It appears that these ISO’s are linked to a nerve bundle that is very similar to the ones we humans have called trigeminal ganglia. They are so sensitive that they can detect the ripple that a drop of water produces on the surface. They can also detect pressures that even the human fingertip can’t detect. This only serves to make them even better predators. The largest concentrations of these sensors appear to be around the mouth near the teeth. The same sensors that enable their deadly accuracy also serve the mothers as they gently assist their eggs in hatching as well as, carrying their young in their mouth without crushing them to death. Never let it be said that these fearsome creatures don’t have a softer and more sensitive side.

For more information, visit Vanderbilt University’s website.

Shopping for Diamonds—in Space

Astrophysicists are hypothesizing that a previously discovered planet could have a diamond interior.

This planet, called 55 Cancri e, is an exoplanet (a planet outside the solar system) that orbits a star called 55 Cancri. Its was the one of the first ‘Super-earths’ to be discovered—its mass is greater than that of earth (around 7.8 times), yet much smaller than the masses of Uranus and Neptune. Estimates of its interior composition and atmosphere had already been made from previous studies observing its transits across the star (similar to the much talked-about Venus transit earlier this year). It was estimated that this planet had a core of iron and silicates, and an envelope of supercritical water (i.e., water in a blurred state between liquid and gas).

However, these estimates were based on the assumption that the planet had an oxygen-rich interior, similar to earth. This assumption is now being challenged in a new model proposed by researchers at Yale University. The star around which the planet orbits itself has a carbon-rich interior, and 55 Cancri e is the closest planet to the star. This led to a new model that the planet could have an interior of carbon instead of oxygen, which could also lead to the observed properties of the planet.

An illustration of the planet 55 Cancri e’s interior. A molten iron core at its center, an outer layer of graphite, and an interior of diamond. [Image Credit: space.com and Haven Giguerre]

However, based on the known temperature and pressure of 55 Cancri e, any carbon in its interior would have to exist in the form of diamond. “This is the first glimpse of a rocky world with a fundamentally different chemistry from Earth. The surface of this planet is likely covered in graphite and diamond rather than water and granite,” said Nikku Madhusudhan, who was the first author on this paper.

If this proves to be true, the phrase ‘like a diamond in the sky’, may turn out to be more than a simile. You can read about this research here and here.

Why Does a Nail on a Blackboard Make Us Cringe?

Why is the sound of nails on a blackboard (and to some of us, even the thought of it) enough to make us wince and cover our ears? Do our ears respond differently to them?

It has been previously known (by brain imaging studies) that in addition to the auditory part of our brain (the auditory cortex), the emotional center of the brain—the amygdala—is also activated by unpleasant sounds. Now how does this dual response work? How are unpleasant sounds represented in the brain? Do specific auditory signals go to the amygdala from the auditory cortex or does it receive them directly? Researchers at Newcastle University have performed a series of experiments seeking to determine precisely this.

The brain scans of 16 participants were obtained in response to a variety of pleasant (bubbling walter, a baby laughing) and unpleasant sounds (a fork scraping glass, nails against a blackboard). Based on these scans, the research team could chalk out the series of events that lead to the disturbed response exhibited upon hearing unpleasant sounds.

Why this aversion to some sounds? [Image Credit: http://myplaceforenglish.blogspot.com]

The sound signals are first processed by the cortex and then transferred to the amygdala. The amygdala, upon recognizing the signal as being ‘unpleasant’, kicks in to transfer a signal back to the auditory cortex, driving it to perceive the sound as even more unpleasant. What this means is that the intense discomfort you experience when you hear an electric drill is driven by an emotional response. “It appears there is something very primitive kicking in,” says Dr Sukhbinder Kumar, the paper’s author from Newcastle University. “It’s a possible distress signal from the amygdala to the auditory cortex.”

The authors also noted that most sounds we classify as unpleasant belong to a high frequency range of the auditory spectrum, the same range in which the sound of a human screaming can be found. Perhaps our aversion to these sounds are thus evolutionary.

This study could be extended to learn more about the generality of this result. Is this specific to unpleasant sounds? What about words with negative connotations? What about words that are merely ‘negative’ but not distinctly unpleasant? The same research methodology can be extended to uncover the mechanisms by which our brain processes auditory information.

You can read about this research here.