What Causes Alzheimer’s? Emma Pallen

Alzheimer’s disease is a chronic neurodegenerative disorder with a wide range of emotional, behavioural, and cognitive symptoms. It is the most common cause of dementia, causing around 60-70% of dementias and is primarily associated with older age, with around 6% of the global population over 65 being affected and risk increasing with age. This is especially concerning considering our ageing population and, by 2040, it is expected that there will be 81.1 million people suffering with Alzheimer’s worldwide. It is also one of the costliest conditions to society, costing the US $259 billion in 2017.

Symptoms of Alzheimer’s can be grouped into three categories. Perhaps the most recognisable category is cognitive dysfunction, which includes symptoms such as memory loss, difficulties with language, and executive dysfunction. Another category of Alzheimer’s symptoms is known as disruption to activities of daily living (ADLs). Initially this can be difficulty performing complex tasks such as driving and shopping, later developing to needing assistance with basic tasks such as dressing oneself and eating. A third category of AD symptoms are related to emotional and behavioural disturbances. This can range from depression and agitation in earlier stages of the disease to hallucinations and delusions as the disease progresses.

What causes Alzheimer’s Disease?

We know that the symptoms of Alzheimer’s are caused by a gross loss of brain volume, also known as atrophy, in a number of regions that progress as the disease develops. As brain tissue is lost, symptoms associated with the function of the lost area emerge, such as personality changes developing as tissue is lost in the prefrontal cortex.

We also know that this brain atrophy is caused by a loss of neurons and synapses in the brain. However, what we don’t know is exactly why this neuronal loss occurs. One way to attempt to solve this question is to compare the brains of Alzheimer’s patients to normally ageing brains. This has led to the observation that the brains of Alzheimer’s patients have two distinct biochemical markers: amyloid plaques and neurofibrillary tangles, which are both abnormal bundles of proteins. While these features are often present to some degree in normal ageing and are not always observed in Alzheimer’s, they are often more associated with specific brain regions, such as the temporal lobe, in Alzheimer’s than in regular ageing. There are a number of theories as to how these biochemical markers may be linked to neuronal and synaptic loss, however none are fully conclusive.

One such theory is the amyloid cascade hypothesis. This hypothesis suggests that amyloid plaques, which are made up of a protein known as amyloid beta, are the primary cause of the disease and that all other pathological features of Alzheimer’s are as a consequence. This theory suggests that the accumulation of amyloid beta into plaques leads to disrupted calcium homeostasis in the cells, which can lead to excitotoxicity and ultimately cell death. Evidence in support of this theory comes from the fact that Down’s Syndrome, a condition in which almost all sufferers display some degree of Alzheimer’s disease by age 40, is associated with a mutation on chromosome 21 which is also the location for the gene coding for Amyloid Precursor Protein (APP), a precursor protein that leads to the formation of amyloid beta.

However, if the buildup of amyloid plaques are the cause of cell death in Alzheimer’s disease, it stands to reason that the removal of these plaques should at the very least stop the progression of the disease, which has not been found to be the case. Furthermore, whilst APP producing transgenic mice do end up having more amyloid beta and amyloid plaques, this does not lead to other features of the disease such as neurofibrillary tangles and most importantly, no neuronal loss. This suggests that there may be some other cause for the neuronal loss seen in Alzheimer’s.

Another theory about the cause of neuronal loss in Alzheimer’s focuses on hyperphosphorylated tau, a protein that is the main component of neurofibrillary tangles. The tau hypothesis suggests that the hyperphosphorylation of tau leads to the formation of these neurofibrillary tangles which can result in depleted axonal transport, a potential cause of cell death. This idea is supported by the fact that the number of neurofibrillary tangles is linked to the degree of observed cognitive impairment. Additionally the progression of where tangles are found is similar to the known progression of atrophy observed in Alzheimer’s. Dysfunction of tau is also known to be linked to another type of dementia, frontotemporal dementia, so it seems plausible that similar mechanisms may be at work in Alzheimer’s.

Whilst these are the two of the most prominent explanations for neuronal death in Alzheimer’s, there are a multitude of other potential explanations, and it is likely that no single explanation will capture all facets of the disease. Rather, it is more likely that there is a complex interplay of biochemical reactions along multiple pathways that lead to the clinical features we see in Alzheimer’s disease. These are likely affected by many other risk factors, such as genetics, or environmental factors such as smoking or head trauma.

A, T, C, G… and more? Adding Letters to Life’s Genetic Code – Alex Marks

Scientists have created bacteria that carries two extra synthetic ‘letters’ of the genetic code.

The genetic code is made from four bases, more commonly known as the ‘letters’, A, T, C and G. It is the order of these ‘letters’ that create the genetic blueprint for all life: DNA. Scientists have modified the bacteria, E. coli, so that it can carry two unnatural ‘letters’ in its DNA.

By adding the extra two ‘letters’, which are named X and Y, scientists have increased the number of combinations that the ‘letters’ could make. These additional combinations could potentially increase the number of biological functions this bacterium could do. The international team of scientists hope that this can lead to the creation of new classes of drugs to treat diseases.

In a standard cell, the four ‘letters’ of the genetic code tell the cell how to make proteins. Proteins are responsible for almost every function and structure within a cell. They repair and maintain the cell; they transport atoms and small molecules; and they make up an important part of your immune system.

By expanding the genetic alphabet from four to six ‘letters’ the potential number of proteins that could be synthesised dramatically increases, allowing for semisynthetic organisms that have new qualities not found anywhere in nature.

It had already been shown that semisynthetic organisms could be created. However, the ones that had been made were slow to replicate and regularly lost their unnatural ‘letters’. The new study has “made this semisynthetic organism more life-like,” according to Prof Romesberg, senior author of the study.

By modifying the existing version of the genetic ‘letter’ Y, the team created a semisynthetic organism that could hold on to the unnatural ‘letters’ X and Y for 60 generations. The scientists believe that the bacterium will keep the letters indefinitely.  Making the DNA is still stable, even with the extra ‘letters’ in it.

“Your genome isn’t just stable for a day,” said Prof Romesberg. “Your genome has to be stable for the scale of your lifetime. If the semisynthetic organism is going to really be an organism, it has to be able to stably maintain that information.”

They managed to make the DNA stable by destroying the bacteria that lost the unnatural ‘letters’. Using CRISPR-Cas9 genome editing tool, the scientist could check the bacteria to see if they had retained X and Y. This tool can read specific parts of the DNA and can also add tags. If the bacteria had not kept X and Y, CRISPR-Cas9 marked them for destruction.

By destroying the unstable bacteria, only the stable bacteria could go on and replicate. By doing this, the scientist’s increased the chance that the replicated bacteria was stable.

“This science suggests that all of life’s processes can be subject to manipulation.” Said Prof Romesberg.

Being able to manipulate processes within cells will help us understand these processes and might be able to help cure diseases.

Pyrolysis – Making Plastic Fantastic

plastic1

Naomi Brown

Since the initial use of plastics in the 50s, over 8.3 billion metric tonnes of plastic have been created – equivalent to the weight of 80 million blue whales!  Of this vast quantity, it is believed that 60% has been discarded in landfill or elsewhere in the environment. Plastic pollution constitutes 90% of waste on the ocean’s surface and has been documented in the bodies of 44% of seabird species.  As none of the mass produced plastics biodegrade readily, we need to consider alternative ways to deal with this waste. Pyrolysis of plastics has been touted as a technology that could solve the problem by breaking down plastic and using it for energy.  

The word pyrolysis comes from the Greek ‘pyro’ meaning heat and ‘lysis’ meaning breaking down. Plastic is made up of long chain molecules called polymers. These chains are degraded by heat and pressure in the absence of oxygen. This forms increasingly smaller molecules.  

The waste plastic is cleaned then placed in a high pressure reactor and heated up to 400 – 500 °C, causing the atoms within the long polymers chains to vibrate to such an extent that the bonds between them break. The plastic does not burn but is melted to a chewing gum consistency. Further heating vapourises it to form a gaseous mixture of different sized molecules, which are separated by a process called fractional distillation.

There are 3 products of plastic pyrolysis: carbon black, liquid oil and hydrocarbon gas. The carbon black can be used in the place of coal or as raw material for making carbon nanotubes. The oil is used to power electricity generators or as a raw material in making petrochemicals, such as lubricants used in manufacturing. The hydrocarbon gas produced is used in the pyrolysis process itself, in order to create the high temperatures required.

Aside from the reduction in waste going to landfill and plastic pollution, there are some other major benefits to using pyrolysis. Only 80% of plastic produced can be physically recycled (the type of recycling where plastic waste is broken down into small granules which are used to manufacture new materials).  In contrast, pyrolysis can be used to break down all plastics.

The process is environmentally friendly: a vacuumed chamber is used, which means toxins are not emitted into the atmosphere, plus the gas is collected and used to power the plant, saving energy for the whole process.

There are also economic benefits to using pyrolysis. Primarily, it is cheaper than disposal in landfill. Implementing the technology is simple and inexpensive and the construction of a pyrolysis plant can be relatively fast. There is the potential that with the introduction of new plants there will be the creation of many new jobs.

A few companies have tried to commercialise pyrolysis in the United Kingdom. One example was Cynar, a plastics-to-fuel company based in London. They constructed their first pyrolysis plant, in Ireland in 2008, with a capacity 20 tonnes per day.   The company set about building further facilities, through partnership deals in Spain and the UK, however the company went into liquidation before completion.  Another company, called Enval, has utilised microwave pyrolysis to recycle plastic aluminium laminates (which cannot be recycled any other way). They have a plant based in Huntingdon, Cambridgeshire, with the ability to process 2000 tonnes per year.  However, no councils are using this type of recycling at the moment. This is because councils have existing contracts with waste management service providers. Hopefully, there will be an increase in the use of pyrolysis as contracts come up for renewal.

Sheffield’s Giant Battery

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Kirsty Broughton

A major step towards greener energy in the UK was taken last month with the opening of an industrial-scale ‘mega-battery’ site owned by E.ON in Sheffield.

The Sheffield site located in Blackburn Meadows is being hailed as the first of its kind in the UK. It has the capacity to store or release 10MW of energy – the equivalent of half a million phone batteries, and is contained in four 40 foot long shipping containers. The batteries are from the next generation of battery energy storage, and can respond in less than a second to changes in energy output – ten times faster than previous models.

Such promising technology has naturally lead to further investments, and the Sheffield site will soon be dwarfed by significantly larger plants. Centrica (the owner of British Gas) and EDF Energy are both in the process of creating 49MW facilities in Cumbria and Nottinghamshire respectively.

When more energy is being put out into the national grid than is being used by consumers, the batteries will take in the excess power and store it. Then, during periods when consumers are using more energy than the grid can provide, the batteries can release this excess energy into the grid, to ensure that everyone has access to power.

This is especially important considering that the UK energy mix is containing an ever-increasing proportion of intermittent sources, such as wind and solar power. June this year saw 70% of the electricity produced from nuclear, wind and solar sources. For the government to hit legally-binding carbon-cutting targets this needs to be the standard for electricity production, but storage is likely to be necessary to balance the intermittency of renewable supplies.

To meet these targets the government introduced a ‘capacity market’ – a subsidy scheme integral to the shake-up of the electricity market. It is designed to ensure energy security particularly during times of high demand, such as the winter months. The scheme has a pot containing £65.9 million, which it will divide between energy suppliers than can guarantee a constant energy supply. It may sound surprising that in the age of austerity the government that is ever-interested in penny pinching is wanting to hand out money. However, it is estimated that the Sheffield site alone could save £200 million over the next four years by increasing energy efficiency. This certainly makes the £3.89 million awarded to E.ON a worthy investment.

E.ON has seen share prices in Germany dramatically fall as it is undercut by abundant, cheaper renewable energy from other suppliers. Germany is often hailed as world leader in renewable energy production, and during a weekend in May of this year 85% of energy production was from renewable sources. E.ON in the UK was following down the same path, as in recent years UK profits have stagnated, and trade has fallen by up to 9%. It was only in March of this year that profits began to pick up again, due to the company shifting away from fossil-fuels and towards green energy production. The battery site in Sheffield is an excellent next step in this major shift.

The Butterfly Molecule

Jonathan James

If you cast your mind back to chemistry class at school, you’ll probably remember learning about various types of atomic bonds. Typically, we think about the way atoms bind to one another in a couple of ways – ionic bonding, where oppositely charged ions are held together by electrostatic interactions, and covalent bonding, in which electrons are shared between atoms. For a long time, these looked like the only types of bonding that could exist under our current understanding of how atoms bind one another, but a recent discovery has unveiled a whole new type of bonding that seems to defy our understanding of chemistry.

Let’s quickly recap what we know about atoms. In the traditional model, atoms are made up of a positively charged nucleus, made up of protons (which give it its positive charge), and neutrons. This nucleus is tiny, and the clear majority of the atom’s size is empty space. Surrounding the nucleus are negatively charged electrons, which orbit in ‘shells’, a bit like planets around the sun (but not really… That could be an article all by itself!) Typically, atoms take up a volume so small, that you could fit 200,000,000,000,000,000 of them inside the dot on this exclamation point!

Recently, however, scientists have been able to confirm a theory that they’ve had since 2002. The existence of ‘Rydberg molecules.’ Affectionately referred to as ‘Butterfly molecules’ because of the butterfly like distribution of the orbiting electrons, Rydberg molecules are enormous. In fact, at a millionth of a meter across (huge for an atom!), they are about the same size as an entire E. coli bacterium. Their electrons are anywhere from 100-1000 times further away from the nucleus than they should be. At these distances, the electrons become ‘super electronically excited’, which allows them to act like a lasso, grabbing nearby atoms and forming weak interactions with them.

The researchers created the molecules by super cooling Rubidium gas to a just above absolute zero, before exciting them into their Rydberg state using lasers. They then kept the atoms under observation, looking for changes in the frequency of light that they would absorb, as this would show that a bond had been formed. Eventually they discovered that they had indeed triggered the formation of these butterfly molecules.

But why should you be excited about this discovery? After all, it’s just another type of dull chemical bond that kids will be forced to learn about, right? Actually, there is a lot of excitement around Rydberg molecules and how they might be used in nanotechnology and small scale electronics to make them much more efficient. There are even hopes that they might be used in quantum computing, pushing technology even more into the future!

Metallic Hydrogen: 80 years in the making

 

Ashley Carley

Rocket fuel, lightning-fast supercomputers and levitating trains are just three uses of the newly discovered metallic hydrogen – if, the Harvard scientists say, everything goes to plan.

Hydrogen is the lightest and most abundant of all the elements. It forms two thirds of every drop of water, and almost 75% of the gas in the Sun’s core. Alone, hydrogen is most often found floating around in its gaseous phase, but it has been predicted a metallic form may exist when exposed to intense pressure.

Two physicists at Harvard University claim to have isolated this incredibly rare form for the first time, in a paper published this week. By squeezing solid hydrogen between two diamonds at temperatures well below freezing, the researchers created pressures larger than those found at the centre of the Earth. In these conditions, the hydrogen atoms began to share their electrons. Using this new electron cloud, they could conduct electricity.

Isaac Silvera, who made the discovery alongside his colleague Ranga Dias, recognises the importance of his achievement, calling it the “holy grail of high-pressure physics.”

This breakthrough has been a long time coming; it has been over 80 years since Eugene Wignar and Hillard Bell Huntington made the first predictions about metallic hydrogen. Since then the goalposts have continually shifted. Estimates of the pressure required to make the substance have been continually revised upwards, from 25 gigapascals (GPa), 250,000 times above atmospheric pressure, in 1935, to the most recent estimate of 400-500 GPa.

Each time the prediction changed, it moved out of the range scientists were capable of recreating in a lab environment, making it somewhat of a carrot on a stick for researchers in the field. Jeffrey McMahon, theoretical physicist at Washington State University, told New Scientist that if the results were reproducible, the recent experiments had solved “one of the major outstanding problems in all of physics.”

It wasn’t easy – the synthetic diamonds had to be flattened, polished and heated to remove any imperfections that could result in cracking. They were then covered in alumina, an extremely hard material made from aluminium and oxygen that hydrogen could not leak through. The two diamonds were then crushed together with great force, and Dr Dias watched as the hydrogen between them turned from clear to black, until it began to shine. The force required was 495 GPa – higher than the pressure at the Earth’s core. Dr Dias then called Professor Silvera, and they took the measurements that would confirm their discovery.

The next step is to see if it retains its structure when compression is relaxed. Some predictions suggest it will be too unstable to survive at room temperature, and will gradually decay, although others have more hope. Graphite forms diamonds under high pressures and temperatures, but when the sources of compression and heat are taken away – the diamond remains. Scientists are hoping metallic hydrogen could act the same way once released from its diamond vice.

If it does, its potential applications are exciting. If the amount of energy used to create the metallic hydrogen can be released by breaking it down again, it could become the most powerful rocket fuel ever made. “We would be able to put rockets into orbit with only one stage, versus two, and could send up larger payloads, so it could be very important,” Professor Silvera says. Electronic systems would also be revolutionised, as “superconductors” could be made which reduce energy wastage in wires.

When Professor Silvera is asked what thinks will happen next, he responds “I don’t want to guess, I want to do the experiment.” After an 80-year wait, perhaps the suspense is great enough.

Tears of sadness and joy

Weilin Wu

Watching The Notebook, cutting onions, or looking at your overdraft are all activities that may lead you to reach for the tissues. But, why do we do cry? Photographer Rose Lynn Fisher has recently captured the microscopic differences between tears of joy, grief, irritation and laughter, but why do different tears appear differently under the microscope?

Well, it seems there are more to tears than meets the eye. Your lacrimal system (the inbuilt waterworks of your body) is actually capable of secreting three different types of tears: Basal, Reflex or Psychic. Basal tears are produced by the eye throughout the day to keep your eye moist and nourished, and you produce on average around 0.75 to 1.1 grams of basal tears in one day. Reflex tears are those that seem to flood your eye like a tsunami, every time you cut into an onion. These tears are produced in response to irritants, such as the sulphuric acid that has formed because of the fumes released by the onion (think of it like the onion’s ultimate revenge). Finally, psychic tears are those tears probably forming in the corner of your eye when you finished that last spoon of Ben and Jerry’s. These psychic tears are produced in response to strong emotions such as sadness, pain or conversely feelings of joy.

But what are tears of joy or grief composed of? Tears are primarily composed of water, salts, antibacterial enzymes and oils, but as some of the photographs taken by Fisher have shown, certain types of tears seem to form unique structures. These intricate patterns produced by different tears, have been found to be a result of the varying levels of hormones such as prolactin and adrenocorticotropic hormones in your tears, which are both released at different intensities in response to stress and emotions. Additionally, the neurotransmitter leucine encephalin, which is your body’s natural painkiller, can also be found in your tears, and may explain why crying can feel good.

Studies investigating why we cry when we feel sad have found that crying helps remove some of the hormones that flush the body when we feel distressed. On the other hand, crying with happiness seems to be a way for your body to neutralise your emotions so you don’t become too overwhelmed. These tiny droplets of emotion then drain from your eye into your nose, hence why your nose runs when you cry. Women have smaller tear ducts than men and so their tears will spill onto their cheeks quicker, providing a brilliant excuse for men to hide those tears shed when watching penguins reunite on Planet Earth II. Or is that just me…

Triggering the waterworks also seems to produce a whole host of other effects such as an increase in heart rate and slowed breathing, which may help to elevate feelings of stress. Babies cry on average, 1-3 hours a day as a way of communication. 22% of patients with Sjorgen’s syndrome, who have difficulty producing tears, have reported that they struggle with identifying and communicating their own feelings. This highlights a possible evolutionary advantage and social function of being able to share our emotions to the world through the act of crying.
So, the next time you feel your bottom lips quiver, and your eyes glaze over, just let it go and have a good ol’ cry; it seems to be good for you.