Can Chocolate be Good for You? The Dark and Light Side of the Force

By Jesica Levingston Mac leod, PhD

It is this time of the year again: San Valentin (aka Valentine’s Day) –  the best excuse to give and more importantly to EAT a lot of chocolate. But, maybe a better gift that receiving chocolate,  is to know that eating chocolate might be good for your health.

In the beginning chocolate was “created” as a medicine –  a healthy beverage –  around 1900 BC by Mesoamerican people. The Aztecs and Mayas gave it the name of “xocolatl”, it means bitter water, as the early preparations of the cacao seeds had an intense bitter taste. Almost one year ago, a longitudinal study, done in the US East Coast, connected eating chocolate with better cognitive function. Yay! Great news, right? The scientists gathered information over a period of 30 years (starting in 1976) from 968 subjects (aged 23-98 years) in the Syracuse-Maine area. The results showed that more frequent chocolate consumption was meaningfully associated with better performance on the global composite score, visual-spatial memory and organization, working memory, scanning and tracking, abstract reasoning, and the mini-mental state examination. Importantly, they pointed out that with the exception of working memory, these relations were not attenuated with statistical control for cardiovascular, lifestyle and dietary factors across the participants.

More good news arrived last summer: an Italian research team announced that flavanol-rich chocolate improves arterial function and working memory performance counteracting the effects of sleep deprivation. The researchers investigated the effect of flavanol-rich chocolate consumption on cognitive skills and cardiovascular parameters after sleep deprivation in 32 healthy participants, who underwent two baseline sessions after one night of undisturbed sleep and two experimental sessions after one night of total sleep deprivation. Two hours before each testing session, participants were assigned to consume high or poor flavanol chocolate bars. During the tests the participants were evaluated by the psychomotor vigilance task and a working memory task, systolic blood pressure (SBP) and diastolic blood pressure (DBP), flow-mediated dilation and pulse-wave velocity. As you might know, sleep deprivation increased SBP/DBP. The result was that SBP/DBP and pulse pressure were lower after flavanol-rich treatment respect to flavanol-poor treatment sleep deprivation impaired flow-mediated dilation, flavanol-rich, but not flavanol-poor chocolate counteracted this alteration. Flavanol-rich chocolate mitigated the pulse-wave velocity increase. Also, flavanol-rich chocolate preserved working memory accuracy in women after sleep deprivation. Flow-mediated dilation correlated with working memory performance accuracy in the sleep condition.

The European Food Safety Authority accepted the following statement for cocoa products containing 200 mg of flavanols: “cocoa flavanols help maintain the elasticity of blood vessels, which contributes to normal blood flow”. This statement means that flavanol-rich chocolate counteracted vascular impairment after sleep deprivation and restored working memory performance. In another study led by Columbia University Medical Center scientists,  dietary cocoa flavanols—naturally occurring bioactives found in cocoa—reversed age-related memory decline in healthy older adults. One possibility is that the improvement in cognitive performance could be due to the effects of cocoa flavonoids on blood pressure and peripheral and central blood flow. Following on this other chocolate attribute, it was shown than weekly chocolate intake may be beneficial to arterial stiffness.

But, there are some bad news!  A review of 13 scientific articles on this topic, provided evidence that dark chocolate did not reduce blood pressure. However, the reviewers claimed that there was an association with increased flow-mediated vasodilatation (FMD) and moderate for an improvement in blood glucose and lipid metabolism. Specifically, their analysis showed that chocolates containing around 100 mg epicatechin can reliably increase FMD, and that cocoa flavanol doses of around 900 mg or above may decrease blood pressure if consumed over longer periods: “Out of 32 cocoa product samples analyzed, the two food supplements delivered 900 mg of total flavanols and 100 mg epicatechin in doses of 7 g and 20 g and 3 and 8 g, respectively. To achieve these doses with chocolate, you will need to consume  100 to 500 g (for 900 mg flavanols) and 50 to 200 g (for 100 mg epicatechin). Chocolate products marketed for their purported health benefits should therefore declare the amounts of total flavanols and epicatechin”.  The method of manufacturing dark chocolate retains epicatechin, whereas milk chocolate does not contain substantial amounts of epicatechin.

The first epidemiological “indication” for beneficial health effects of chocolate were found in Kuna natives in Panama with low prevalence of atherosclerosis, type 2 diabetes, and hypertension. This fact correlated with their daily intake of a homemade cocoa. These traits disappear after migration to urban and changes in diet.

 

There are many  claims about the potential health benefits of chocolate, including anti-oxidative effect by polyphenols, anti-depressant effect by high serotonin levels, inhibition of platelet aggregation and prevention of obesity-dependent insulin resistance. Chocolate contains quercetin, a powerful antioxidant that protects cells against damage from free-radicals. Chocolate also contains theobromine and caffeine, which are central nervous system stimulants, diuretics and smooth muscle relaxants, and valeric acid, which is a stress reducer. However, chocolate also contains sugar and other additives in some chocolate products that might not be so good for your health.

 

Oh well, maybe the love of chocolate is like any other romantic affair: blind and passionate. Apparently, the beneficial dosage is 10 g of dark chocolate per day (>70% cocoa), so enjoy it as long as the serotonin boost for rewarding yourself with a new treat last.

 

Happy Valentine’s Day!

 

 

A Short History of Fast Radio Bursts

 

By JoEllen McBride, PhD

Humans have gazed at the stars since the beginning of recorded history. Astronomy was the first scientific field our distant ancestors recorded information about. Even now, after thousands of years of study, we’re still discovering new things about the cosmos.

Fast radio bursts (FRBs) are the most recent astronomical mystery. These short-lived, powerful signals from space occur at frequencies you can pick up with a ham radio. But don’t brush the dust off your amateur radio enthusiast kit just yet. Although they are powerful, they do not occur frequently and happen incredibly fast. Which is exactly why astronomers only recently noticed them. The first FRB was discovered in 2007 from data taken in 2001. The majority of FRBs are found in old data. Their short duration meant astronomers overlooked them as background signals but closer inspection revealed a property unique to radio signals originating from outside our galaxy.

 

Signal or Noise?

Radio signals are light waves with very long wavelengths and low frequencies. Visible light (the wavelengths of light that bounce off objects, hit our eyes and allow us to see) happens on wavelengths that are a few hundred times smaller than the thickness of your hair. The wavelength of radio waves can be anywhere from a centimeter to kilometers long. The longer the wavelength, the lower the frequency  and more the signal is delayed by free-floating space particles. This is because space is not a perfect vacuum. There is dust, atoms, electrons and all kinds of small particles floating around out there. As light travels through space, it can be slowed down by these loitering particulates. Larger distances mean more chances for the light to interact with particles and these interactions are strongest at the lowest frequencies where radio waves happen.

Radio signals from within our own galaxy are close enough that they are not really affected by this delay. But sources far outside of the Milky Way have very large distances to travel so by the time the signal reaches our telescopes, it has interacted with many particles. This produces a streak or a ‘whistle’ where the higher radio frequencies in the signal reach our telescopes first and the lower ones arrive shortly afterwards.

When astronomers started noticing these whistles at unexpected frequencies, they no longer believed they were background noise but signals from the far reaches of space. They needed another piece to the puzzle though to determine exactly what was causing these interstellar calls.

 

It Takes Two to Find a FRB

The signals discovered in previous data appeared to be one-and-done events, which meant they could not be observed again with a bigger telescope to get a more precise location. Without a precise position on the sky, astronomers couldn’t tell where the signals were coming from, so had no idea what was producing them. What astronomers needed was a signal detected by two different telescopes at the same time. One telescope to broadly search for the signal and a second, much larger telescope to accurately determine its location. So they began to meticulously watch the sky for new FRBs. The first real-time observation of an FRB was in May of 2014. Although it was observed by only one telescope so its precise location was unknown, it gave astronomers a way to detect future ‘live’ bursts. In May and June of 2015 a search by another team of astronomers yielded the first ever repeating FRB.

The Arecibo radio telescope (yes the one from Goldeneye) detected the first signals then they requested follow-up observations from the Very Large Array to more precisely pin-down the location. Once they had a location, yet another team of astronomers could take pictures at visible frequencies to see what was lurking in that region of space. They found a teeny tiny galaxy, known as a dwarf galaxy, at a distance of 3 billion light years from Earth. This galaxy is full of the cold gas necessary to create new stars which means many stars are being born and the huge, bright ones are living quickly and dying.

 

Who or What is Calling Us?

Where the FRBs are coming from is important because it allows astronomers to pick between the two plausible theories for what causes FRBs. The energy produced by these bursts is impressive, so the most likely culprits take us into the realm of the small and massive: supermassive black holes (SMBH) and neutron stars. One idea suggests that FRBs could be the result of stars or gas falling into the SMBH at the center of every galaxy. If this were the case, we would expect the FRBs to occur in the central regions of a galaxy, not near the edges. Neutron stars, on the other hand, are formed after the death of massive stars. These stars are typically 10 to 30 times more massive than our Sun, so do not live for long. Astronomers expect a galaxy creating lots of new stars to also create lots of neutron stars as the most massive stars die first. Star formation can occur anywhere in a galaxy but is most commonly observed in the outer regions.

This repeat FRB is located pretty far from the center of a galaxy going through a period of intense star birth so this lends credence to neutron stars being the source. Of course, we are looking at a single data point here. There is no reason to suspect that there is a single cause for FRBs. We need more real-time observations of FRBs so we can figure out where they are located and whether or not they always come from dwarf galaxies. FRB searches have been added to three radio frequency surveys, known as CHIME, UTMOST and HIRAX, that will detect and locate these powerful signals with great precision.

It looks like we can continue to look forward to another few millennia of cosmic discoveries.

End Crisis, Bridges and Scattered Genes: Chromatin Bridges and their Role in Genomic Stability

By Gesa Junge, PhD

Each of our cells contains about two meters of DNA which needs to be stored in cells that are often less than 100uM in diameter, and to make this possible, the DNA is tightly packed into chromosomes. As the human cell prepares to divide, the 23 pairs of chromosomes neatly line up and attach to the spindle apparatus via their middle point, the centrosome. The spindle apparatus is part of the cell’s scaffolding and it pulls the chromosomes to opposite ends of the cell as the cell divides, so that every new daughter cell ends up with exactly one copy of each chromosome. This is important; cells with more or less than one copy of a chromosome are called aneuploid cells, and aneuploidy can lead to genetic disorders such as Down Syndrome (three copies of chromosome 21).

In some cancer cells, chromosomes with two centromeres (dicentric chromosomes) can be detected, which can happen when the ends of two chromosomes fuse in a process called telomere crisis. Telomeres are a sort of buffer zone at the ends of the chromosome which consist of repeats of non-coding DNA sequences, meaning there are no genes located here. As one of the DNA strands is not replicated continuously but in fragments, the telomeres get shorter over the lifespan of a cell, and short telomeres can trigger cell cycle arrest before the chromosomes get so short that genetic information is lost. But occasionally, and especially in cancer cells, chromosome ends fuse and a chromosome becomes dicentric. Then it can attach to the spindle apparatus in two points and may end up being pulled apart as the two daughter cells separate, sort of like a rope tied to two cars that drive in opposite directions. This string of chromosome is referred to as a chromatin bridge.

Researchers at Rockefeller University are studying these chromatin bridges and what their relevance is for the health of the cell. A paper by John Maciejowski and colleagues found that the chromatin bridges actually stay intact for quite a long time. Chromosomes are pretty stable, and so the chromatin bridges lasted for an average of about 9 hours (3-20h) before snapping and quickly being pulled back into the original cell (see video). Also, the nucleus of the cell was often heart-shaped as opposed to the usual round shape, which suggests that the chromatin bridge physically pulls on the membrane surrounding the nucleus, the nuclear envelope. Indeed, proteins that make up the nuclear envelope (e.g. LAP2) were seen on the chromatin bridge, suggesting that they take part of the nuclear envelope with them as they divide.  Also, cells with chromatin bridges had temporary disruptions to their nuclear envelope at some point after the bridge was resolved, more so than cells without chromatin bridges.

The chromatin bridges also stained positive for replication protein A (RPA), which binds single stranded DNA. DNA usually exists as two complementary strands bound together, and the two strands really only separate to allow for DNA to be copied or transcribed to make protein. Single-stranded DNA is very quickly bound by RPA, which stabilises it so it does not loop back on itself and get tangled up in secondary structures. The Rockefeller study showed that a nuclease, a DNA-eating enzyme, called TREX1 is responsible for generating the single-stranded DNA on chromatin bridges. And this TREX1 enzyme seems to be really important in resolving the chromatin bridges: cells that do not have TREX1 resolve their chromatin bridges later than cells that do have TREX1.

So how are chromatin bridges important for cells, the tissue and the organism (i.e. us)? The authors of this study suggest that chromatin bridges can lead to a phenomenon called chromothripsis. In chromothripsis, a region of a chromosome is shattered and then put back together in a fairly random order and with some genes facing the wrong direction. Think of a new, neatly color-sorted box of crayons that falls on the floor, and then someone hastily shoves all the crayons back in the box with no consideration for color coordination or orientation. Chromothripsis occurs in several types of cancers, but it is still not really clear how often, in what context and exactly how the genes on a chromosome end up in such a mess.

According to this study, chromothripsis may be a consequence of telomere crisis, and chromatin bridges could be part of the mechanism: A chromosome fuses ends with another chromosome and develops two centromeres. The dicentric chromosome attaches to two opposite spindles and is pulled apart during cell division, generating a chromatin bridge which is attacked by TREX that turns it into single-stranded DNA, the bridge snaps and in the process the DNA scatters, and returns to the parent cell where it is haphazardly reassembled, leaving a chromothripsis region.

The exact mechanisms of this still need to be studied and the paper mentions a few important discussion points. For example, all the experiments were performed in cell culture, and the picture may look very different in a tumor in a human being. And what exactly causes the bridge to break? Also, there are probably more than one potentially mechanism linking telomere crisis to chromothripsis. But it is a very interesting study that shines some light on the somewhat bizarre phenomenon of chromothripsis, and the importance of telomere crisis.

Reference: Maciejowski et al, Cell. 2015 Dec 17; 163(7): 1641–1654.