The Role of Crystallins in Maintaining Lens Transparency

Crystallins are adapted not to crystallise; the eye lens needs to be a highly concentrated solution, but it needs to avoid small crystals or aggregates, since they would scatter light and make the lens opaque. Our lenses achieve this by mixing together several different crystallins, which together form a uniform, glassy solution. The protein molecules are arranged in a way which means that their refractive index is nearly the same as glass- which makes the lens transparent. This is due to the small size of the protein molecules, less than 10 nm in diameter, and their close packing at high concentration

The lens contains three major types of crystallins, making up about 90% of the protein. Alpha crystallins are the most common. They are composed of two similar types of protein chain, which associate to form large spherical complexes containing about 40 chains. These large spheres repel one another and distribute themselves throughout the lens cells. Beta crystallins, shown here from, also form oligomeric complexes (contains a limited number of monomers), typically formed of two or six copies of the chain. There are several similar beta crystallins, which can mix and match to form a bunch of different types of oligomers. Finally, gamma crystallins are monomeric, and serve as a weak glue to gently bind the alpha crystallins together.

Our crystallin proteins need to last our entire life, so the lens contains a powerful method to protect them. Alpha crystallin acts as chaperone, finding damaged proteins and binding to them before they can form translucent or opaque complexes. Unfortunately, in spite of this protection, the damage builds up as we age, as crystallins are broken or unfolded or oxidized. Slowly, the damage leads to progressive build-up of opaque aggregates, leading to cataracts. 

The NHS

The NHS was launched in 1948. It was born out of a long-held concept that healthcare should be available to all, regardless of wealth – one of the NHS's core principles. With the exception of some charges, such as prescriptions, optical services and dental services, the NHS in England remains free at the point of use for all UK residents. This currently stands at more than 64.6 million people in the UK.

The NHS in England deals with over 1 million patients every 36 hours. It employs more than 1.5 million people, putting it in the top five of the world’s largest workforces, alongside the US Department of Defence, McDonalds, Walmart and the Chinese People’s Liberation Army.

The NHS in England is the biggest part of the system by far, catering to a population of 54.3 million and employing around 1.2 million people. Of those, the clinically qualified staff include 150,273 doctors, 40,584 GPs, 314,966 nurses and health visitors, 18,862 ambulance staff, and 111,127 hospital and community health service (HCHS) medical and dental staff. The NHS in Scotland, Wales and Northern Ireland employs 161,415; 84,000 and 66,000 people respectively.

Funding for the NHS comes directly from taxation. Since the NHS transformation in 2013, the NHS payment system has become underpinned by legislation. The Health & Social Care Act 2012 moves responsibility for pricing from the Department of Health, to a shared responsibility for NHS England and NHS Improvement. The purpose of the 2012 act was to devolve decision-making from a centralised NHS to local communities, with the intent of making it more tailored to specific needs. The act aimed to put patients at the centre of the NHS, change the emphasis of measurement to clinical outcomes, and empower healthcare professionals, in particular GPs.


When the NHS was launched in 1948, it had a budget of £437 million (roughly £15 billion today).For 2015/16, the overall NHS budget was around £116.4 billion, with NHS England  managing £101.3 billion of this.

CRISPR-Cas9

CRISPR-Cas9 is a genome editing tool that is revolutionary in the scientific world. It is faster, cheaper and more accurate than previous techniques of editing DNA and has a wide range of potential applications.

It is a unique technology that enables genetic scientists to edit parts of the genome by removing, adding or altering sections of the DNA base sequence. CRISPR is currently the simplest and most precise method of genetic manipulation in the scientific community.

The CRISPR-Cas9 system consists of two key molecules that are able to alter DNA. These are:

•  an enzyme called Cas9- which acts as a pair of ‘molecular scissors’ that can cut the two strands of DNA at a specific location in the genome so that DNA can be added or removed (the generic type of molecule is called a restriction enzyme).
•  a piece of RNA called guide RNA (gRNA), which consists of a small piece of pre-designed RNA sequence (about 20 bases long) located within a longer RNA scaffold. The scaffold binds to DNA and the pre-designed sequence ‘guides’ Cas9 to the right part of the genome, ensuring the right DNA sequence is changed.

The guide RNA is designed to find and bind to a specific sequence in the DNA. The guide RNA has RNA bases that are complementary to those of the target DNA sequence. This means that, in theory, the guide RNA will only bind to the target sequence and no other regions of the genome, meaning that only the preferred section of DNA is altered.
The Cas9 follows the guide RNA to the relevant location in the sequence and cuts across both strands of the DNA. At this stage the cell recognises that the DNA is damaged and tries to repair it. It can theoretically change both alleles of a gene.

Forensic psychiatry

Psychiatry is defined as the study and treatment of mental illness, emotional disturbance, and abnormal behaviour. Psychiatry is a medical specialty, and so psychiatrists need to be medically trained to perform this type of medicine. This is the main difference between psychiatry and psychology; which can be defined as the study of behaviour and the mind, and can be thought of more as a social science. Forensic psychiatry is a specialised branch of psychiatry which deals with the assessment and treatment of mentally ill offenders in prisons, secure hospitals and the community. It is a particular aspect of psychiatry which I find interesting as it has extreme consequences in terms of the threat posed to society.

Forensic psychiatrists provide psychiatric treatment in a secure environment or where patients are subject to legal restrictions- meaning that the doctor needs an in-depth understanding of criminal, civil and case law as it relates to patient care in these settings. Treatment areas can vary from high security rural prisons to community centres. Referrals can range from those who have committed minor offences to serious and violent offenders, and for this reason the day of a forensic psychiatrist is never the monotonous. Forensic psychiatrists may also assess non-offenders displaying high-risk behaviour. Forensic psychiatrists also provide specialist advice to courts, probation services, and the prison service. They also prepare reports for mental health review tribunals, hospital managers’ hearings, other practitioners and criminal justice agencies.

Expert opinions given to court:

• ·         defendant’s fitness to plead and fitness to stand trial
• ·         capacity to form an intent
• ·         advice to the courts on the available psychiatric defences
• ·         appropriateness of a mental health disposal at the time of sentencing
• ·         nature of a particular mental disorder and link to future risks
• ·         prognosis and availability of “appropriate treatment”
• ·         level of security required to treat a patient and manage risk

Dendrocnide moroides aka “gympie gympie”

The Dendrocnide moroides has been said to be the plant with the most excruciating sting in the world- injuring and sometimes killing dogs, horses, and even humans. The species is relatively common in Queensland, and is native to the warm forests of northern Australia; typically growing 1.5-2 meters in height. The plant has large, thin heart-shaped leaves, which are covered in small silica-tipped hairs, which are extremely efficient at penetrating the skin of its victims. Contact with these hairs causes the release of the potent toxin moroidin, which causes the long list of agonising symptoms. One reason why the plant is extremely dangerous is that the hairs are very loosely fitted to the cuticle of the leaf, meaning that with light winds, the hairs can be blown off the plant and cause irritation if it comes into contact with an animal. On case of the sting resulted in suicide, after a man accidently used a leaf as a piece of toilet paper. The hairs of the plant can be embedded in the skin, and can remain there if no appropriate treatment has been given, which results in long-term pain and discomfort, which is one of the reasons why the plant is so feared- as the symptoms can sometimes last for weeks, if not months.

Moroidin is the active chemical in the toxin of the plant, and is a bicyclic octapeptide. Its skeletal formula is shown on the adjacent diagram, and it has a molecular formula of  C₄₇H₆₆N₁₄O_{10. It is made of 9 different amino acids.} 

The recommended treatment for skin exposed to the hairs is applying diluted hydrochloric acid and then pulling out the hairs with a hair removal strip. Tweezers or sticky tape can also be used, but care needs to be taken when removing the hairs, as if broken they will worsen the pain.

The Impacts and Management of HIV in Uganda

Impacts of the Disease

HIV puts economic stress onto the young and the old, as they have to provide for the family if their relative who is of a working age is infected with HIV. This is made worse by the fact that 58% of all jobs are in the primary sector- using resources directly from the land- meaning that the young and the old are physically strained by work which they are forced to do in order to survive, which is not suitable for their body or their age. This also means that instead of farming and then selling their produce for money, they are forced into subsidence farming (providing for themselves alone), as they need to survive. This decrease in agriculture is also producing a huge loss or workforce across Uganda, which is directly impacting its GDP as a country. This, therefore is undoing decades of economic progress made by Uganda, and is hindering its economic development massively.

The financial costs of caring for patients with HIV/AIDS can also be huge, relative to total household income. In the Rakai district, households reported spending up to a third of their total annual income on medical care for one month, or for a funeral. This then puts more strain on the carers to make more income, putting huge amounts of economic and emotional stress on the already-vulnerable age groups. This could lead to mental problems such as depression and high levels of anxiety, which sometimes causes suicide, especially prevalent amongst young people.

HIV affects Uganda’s healthcare in 2 ways: it increases the number of people in need of services, and healthcare specifically for HIV is a lot more expensive than for other infectious diseases. By 1993, 54% of the admissions in Rubaga hospital (on the outskirts of Kampala), were HIV-positive and mortality rate of these patients was 17.4%, as oppose to the mortality rate for those not infected, which was 5.8%. Hospital occupancy rates has increased due to the huge amount of people seeking help with their HIV, and so this is putting a huge strain on the health sector in Uganda, which is already under massive amounts of pressure, given the high number of people with other infectious diseases such as malaria, TB and cholera, which require lots of medical attention.

The transmission rate in Uganda is also extremely high from lack of education about the disease, resulting in more cases, more poverty and more strain on both private and public resources. This could also be due to the fact that there is still a huge social stigma around HIV, and so high risk groups aren’t aware that the person they are getting it from even has HIV.

Education in Uganda is also extremely low, with the only 53.3% of children finishing primary school in 2011. This is somewhat due to children having to act as carers for sick relatives, or having to work to gain income for the family. This results in families being trapped in the poverty cycle because if people aren’t educated they can’t receive a high-paying specialised job, resulting in a very low income and poverty.

Management Strategies

The main approach to preventing HIV in Uganda is known as the ABC system:

·         Sexual abstinence

·         Be faithful to a single partner or reduce the number of partners

·         Always use a condom

This means that high risk groups are less likely to get/pass on HIV, as the number of unsafe sex encounters are drastically reduced. This initiative started when the government realised that the number of Ugandans who reported using condoms at their last sexual experience was at 13.7 percent in 2011. People, however, tend to not follow this advice, or are forced into having unsafe sex due to either domestic violence, rape culture or prostitution. This campaign is a change from abstinence-based approaches to prevention, which became dominant in previous years due to PEPFAR's significant investment of money for these types of programme. Delaying sex until marriage is hoped to reduce HIV infection rates among young people, and billboards across various cities in Uganda widely advertise this. However, ignoring the importance of condom use is contributing to rising HIV rates, showing how important all three areas of the ABC approach are.

A community-based organisation called The AIDS Support Organisation was set up in 1987 to help people come to terms with their disease and try and reduce the taboo of HIV, and was one of the first action groups in Uganda to help those with HIV.

Prevention of mother-to-child transmission (PMTCT): expectant mothers are encouraged to know their HIV status in Uganda, as this seriously affects the health of their baby. Around 94 percent of pregnant women who attended antenatal clinics in Kampala received counselling and testing for HIV in 2011, which suggests that knowledge about PMTCT is relatively high in the capital, however, this is only true for the women who went to antenatal clinics, which is around 68% of the city.

The World Bank has also significantly contributed to the HIV healthcare of Uganda, as it has donated a total of over $100 million dollars on HIV prevention and treatment over the last 50 years- drastically improving the prevalence of the disease in the last decade.

Uganda’s government has also ‘mainstreamed’ HIV issues in its Poverty Eradication Plan- raising awareness of the disease, various prevention methods and the socio-economic stress put on a large segment of the population.

Trichromatic vision in Humans

The human eye is the visual pathway to the world around us, and enables most of us to see thousands upon thousands of different colours. As shown in figure 1, the human eye is a very complex organ, with many different structures help us get the best vision in different situations- dim or bright etc. - and when all of these parts perform in harmony, we are able to see clearly.

In order to understand how we see different colours, it is first imperative to understand how the eye works as a unit: the starting point of vision is when light rays reflect off an object and enter the eyes through the cornea-the outermost, transparent layer of the eye. The rays are then refracted by the cornea and pass through the pupil- a whole created by the iris to control the amount of light passing through it. After that the rays pass through the lens- which can bulge or shrink to further refract the rays in order to focus them on the retina at the back of the eye.

The retina is an extremely thin layer of cells at the back of the eye which contains millions of light-sensitive cells called rods and cones- and are also known as photoreceptors. Cones are concentrated in the center of the retina (the macula) and in bright light conditions, they provide precise vision and detect colours. Rods however, are located outside the macula and extend all the way to the outer edge of the retina. They provide peripheral vision and allow the eyes to detect motion and help us see in dim light and at night. These photoreceptors then convert the light into electrical impulses which are sent to the brain via the optic nerve at the back of the eye, and create an image in our head.

As previously mentioned, we are able to see colours due to cone photoreceptors, of which there are 6-7 million of in the retina of each eye. Most of them are located in a 0.3mm spot on the retina called the fovea centralis, and over the last few centuries experiments have given evidence that amoung these cones there are three different types of colour reception: red (64%), blue (2%) and green (34%). This was proved by two different groups of scientists: Wald and Brown at Harvard, and Marks, Dobelle and MacNichol at Hopkins in 1959. However, the first original theory of there being three different light sensitive ‘particles’ was put forward by Thomas Young in 1802, 136 years after Sir Isaac Newton’s famous discovery that white light contained thousands of different colours (due to their different wavelengths on the electromagnetic spectrum), and so enabled us to understand where colour ‘comes from’.

"Colour is the visual effect that is caused by the spectral composition of the light emitted, transmitted, or reflected by objects” and when a light ray of a certain wavelength hits the fovea centralis, it activates the three different types of cone to varying degrees, and with an infinite amount of varying combinations, we are able to see thousands of different colours. This is shown in a simplified diagram in figure 3, but in reality this diagram would be a lot more complex because of the ranging number of shades which belong to each colour. To prove that any colour visible to humans can be created from this trichromatic system, we can use the example of TV sets; if you look at a normal television up close when it is switched on, the tiny pixels contain just 3 colours: red, blue and green (as shown in figure 4).

The human eye can perceive many more variations in warmer colours than cooler ones due to the fact that almost 2/3 of the cones process longer light wavelengths and so we are able to see more yellows, oranges and reds. Additionally, the reason we can’t see colours in the dark is because the rods ‘take over’ to control the amount of light that we see, and so the cones aren’t in control anymore. Furthermore, about 8% of men and 1% of women have some type of colour impairment; the most common of which is red and green dichromatism, which causes the colours red and green to appear indistinguishable.

In conclusion the reason why humans can see thousands upon thousands of different colours is that, despite only having 3 types of cone photoreceptor, the cones send-off varying amounts of blue, red and green to the optic nerve to be carried to the brain, and by changing these amounts of light, all of the colours in the visible spectrum can be produced.