ScienceMind Winter 2022 (Issue 10)

Dear Reader,

I hope you are enjoying the new year and new academic semester! In this issue you will find articles in the categories of Genetics, Immunology, Physical Science, Endocrinology, Technology, Psychiatry and Neuroscience. I hope you enjoy reading them as much as we enjoyed creating them Special thanks to the writing, editing and designing teams for making this happen!

The last few months our committee members have been working hard to expand the society beyond this magazine and make it more engaging for you, our readers, and society members Our events organizer, Laia, has planned some amazing events so stay tuned to see what's on! We are also excited to announce our collaboration with Lessgo, an app that enables you to design plans with your social circles.

If this is your first time reading our magazine Science Mind is the award-nominated, student-led science magazine of King's College London, which focuses on reporting recent findings in the main branches of science to students and the wider community We aim to showcase and develop the written and oral communication skills of students interested in research by concisely explaining complex scientific concepts in the form of lay articles and conducting interviews. Authors can also broaden their knowledge by writing articles for different sectors between issues

If science communication is a concept that interests you, I encourage you to join the dynamic and constantly expanding team of ScienceMind. We would love to have you on our team! Have a wonderful day

Yours faithfully,

The Deputy Editor-in-Chief

Rosa Tsucala

Behavioural genetics: A historical perspective

Biology is often seen by many as the least impressive of the STEM

subjects and hopefully this review shall show that genetics in particular has had its fair share of intrepid genius explorers that put their careers on the line in pursuit of answers to crazy questions. This article shall explore three of the greatest questions in biology and review a revolutionary approach devised in the 1980s to tackle them

Our story starts at Columbia university in 1908 with a 42 year old scientist called Thomas Hunt Morgan. Those of you familiar with genetics will know why Thomas Morgan is an important geneticist He was the first person to start working with the fruit fly or Drosophila Melanogaster in a meaningful way. He started a lab that would eventually come to be known as Morgan’s Fly lab and could be seen by some as the place where modern classical genetics was born Thomas Morgan used his fruit flies to study heredity and did a large number of genetic crosses, eventually

WRITTEN BY ALEXI MERY EDITED BY ANASTASIIA TARASENKO DESIGNED BY WINNIE (WING YIN) LIU

linking chromosomes to inheritance

He also tried inducing mutations using radium and X-rays but his method to identify mutants was not sensitive enough to pick all of them up. Eventually, T.H Morgan would go on to win the Nobel Prize in Physiology or Medicine in 1933 precisely for establishing this link and discovering how chromosomes convey hereditary information

One of the most important breakthroughs that T.H Morgan came up with was the idea of crossing over He came up with this idea to explain a curious phenomenon that we would now define as gene linkage This is the concept that some genes seem to always be inherited together and others less so If genetic material could be exchanged from one chromosome to another during a process such as crossing over, then genes that are close together are less likely to separate compared to genes that are closer together

Morgan's fly lab opens 1908

Gregor Mendel discovers his laws of inheritence 1900

Sturtevant publishes the first genetic map 1913

The above breakthrough led a 19 year-old undergraduate student in Morgan’s lab, Alfred Sturtevant, to suggest that a mathematical formula could be determined to predict the distance between two genes Moreover, if the distance between several genes was determined, you could create a kind of genetic map to visualise where genes are found relative to one another. The unit of distance in these genetic maps is the ‘Morgan’ and is equal to the crossover or recombination frequency, expressed as a percentage

Thomas Morgan and Alfred Sturtevant ushered in a golden age for genetics and would make it possible for a new generation of scientists to tackle a wide range of new problems. The next important player to enter onto the stage were the phage biologists and they would later become known as the Phage group These include Salvador Luria, Max Delbruck, James Watson and Seymour Benzer, the latter of which will become of vital importance later in the story. These scientists would start the field of molecular biology. However, these fascinating scientists seem to have become all but forgotten

The phage group was started in the 1940s by the German, Max Delbruck He initially trained as a physicist but he was inspired to study biology by Niels Bohn and Wolfgang Pauli Max Delbruck started his work in biology by looking at how mutations work and he wanted to find a simple biological system to do this. Bacteriophages, which are viruses that infect bacteria, seemed like the perfect system to study Soon after, Delbruck met Salvador Luria, a fellow physicist turned biologist in 1940 and they both started working on the phages.

Delbruck and Luria studied several aspects of phage biology, from their replication patterns to their effects on cells In particular, these two scientists studied these processes in a quantitative way, thus making their science far more precise This allowed for the scientists working in phage biology to start thinking mechanistically and this would pave the way for what would soon be a golden age in molecular biology Some of the basic phage biology they discovered some of you will have heard of, including how the lytic and lysogenic phases of bacterial replication work, how to identify mutations and they described the viral life cycle

Delbruck-Luria experiment showed that mutations arise spontaneously 1943

T.H Morgan wins the Nobel Prize in Physiology or Medicine

Max Delbruck starts working on phages

Salvadore Luria starts working with Max Delbruck

The above work made both Delbruck and Luria legends in the genetics world and inspired other scientists to enter the field One of the first to join was Alfred Hershey, a chemist who studied antigens The three men informally collaborated a great deal and they had as their base the biology lab at Cold Spring Harbour in Long Island, New York. Prior to this landmark experiment, Hershey discovered that phages have several different genes and that phages can undergo genetic recombination In 1952, Alfred Hershey and Martha Chase discovered that only nucleic acids were transmitted from viruses to bacteria and were the genetic material of bacteria, ending the idea that genes are made of proteins

Moreover, in 1945, Erwin Schrodinger published his massively influential book ‘What is Life?’ which described how biology might need a new kind of physics to be explained. Schrodinger argued that several biological phenomena seemed to go against the most fundamental laws of physics, in particular the second law of thermodynamics which states that the universe tends towards a greater level of disorder (entropy). This book would attract a multitude of physicists into biology, including names such as Seymour Benzer, Francis Crick and Maurice Wilkins In many ways, this one book

opened up the path for the discovery of the structure of DNA

We can now turn to the scientist who in many ways is the protagonist of our story A man who hated standing still and who felt the need to go from one obscure field to another and shed a beam of insight onto it, opening the door to follow in his footsteps. His name is Seymour Benzer In 1947, two years after ‘What is life?’ was published, Benzer was finishing his PhD in physics from Purdue University where he was working on solid-state physics In fact, his research would contribute to the development of the transistor, a central electronics component that would open the way for the creation of computers

Benzer met Max Delbruck at Caltech and even did a 2 year postdoc working under him This completely converted Benzer to the world of the phage He then went to the Laboratory of Molecular Biology (LMB) at Cambridge where he met Francis Crick and worked with him for a bit It was at around this time that Benzer made his first major contribution to biology He made a genetic map of the rII phage’s genome and discovered that genes were composed of different bases and were not indivisible units themselves As some of you might

Erwin Schrodinger publishes his book 'What is Life?'

Erwin Chargaff discovers his so-called 'Chargaff rules'

Avery MacLeod and McCarty experiment

Hershey and Chase experiment

have guessed, the method Benzer used to do this was Alfred Sturtevant’s technique of gene mapping

However, around this time, many scientists had caught on to the formidable potential of molecular biology, which led Seymour Benzer to leave the field. He then decided to tackle an even more formidable question: how genes influence behaviour Benzer’s approach to this question would be completely revolutionary He wanted to find a model organism with which it would be possible to identify the relationship between single genes and the changes in behaviour that these genes might cause, which was a massively risky approach because scientists were not convinced that single genes could lead to behavioural changes The risk therefore was ending up with fly mutants that actually had mutations in a large number of different genes and that would yield very little insight as to the exact proteins and cellular mechanisms controlling behaviour

The scientist that would end up helping Benzer in this quest was Roger Sperry It was thanks to Sperry that Benzer got to work with a large number of model organisms

and in the end, he settled with using Drosophila This was hardly a surprising choice considering that Drosophila had already made significant contributions to genetics in the past, in particular through the work of T H Morgan It was therefore at Caltech, with Seymour Benzer, with immense skepticism from Benzer’s colleagues, that the field of behavioural genetics or neurogenetics was born This field, as the name suggests, is interested in uncovering the genetic basis of behaviour

One of the first behaviours that Benzer chose to study was that of how fly phototaxis, or how flies move with regards to light The ‘normal’ response flies have to light is to move towards it However, Benzer’s idea was that certain mutant flies might exhibit a different response To test this hypothesis, he developed an apparatus which he called a countercurrent machine (see figure 1) Once Benzer was satisfied with his apparatus, he then used EMS (Ethane methyl sulfonate) to induce mutations in the flies. This method is called a mutagenesis screen and is still used in molecular biology and genetics labs today. This method allowed Benzer to identify a large number of light avoiding fly mutants such as photophobe

Strcuture of DNA is discovered

Seymour Benzer enters the field of behavioural genetics

James Watson, Francis Crick and Maurice Wilkins win the Nobel Prize in medicine

The power of Benzer’s method started attracting other scientists to his lab, notably Ronald Konopka. Konopka was particularly interested in understanding how organisms can have a sense of time, and had worked with an expert in the field of chronobiology, the study of how organisms develop a sense of Time This meant that Konopka knew exactly the direction he wanted to take when he came to work with Seymour Benzer Amazingly, flies

have a sense of time since they only emerge from their eggs at dawn This meant that by isolating flies that did not follow this pattern, it might be possible to isolate the gene responsible for this phenomenon

Konopka managed to isolate several of these mutants which then became known as clock mutants. What Konopka discovered was that several of those had a mutation in a single gene that Konopka appropriately named the period gene This had a very profound implication in that it suggested that circadian rhythms are controlled by a very small number of proteins. This discovery was published in a landmark paper in 1971 that is now seen as one of the most important papers in the field of chronobiology (the study of cyclical physiological patterns biology) It would take another 15 years before the period gene was fully cloned.

As shown above, Benzer’s method did not provide direct mechanisms to explain why the mutants had the change in behaviour observed, but it did provide a starting point for other scientists Behavioural genetics allowed scientists to answer questions that had never really been reachable before. For instance, scientists studying Drosophila could not help but be amazed by their

Figure 1 A sketch Benzer’s countercurrent apparatus to study phototaxis in Drosophila (taken from Benzer, 1967)

Hall, Rosbash and Young clone the period gene

Fruitless gene cloned by Jeffrey Hall

Hall, Rosbash and Young win the Nobel Prize in Medicine 2017

Konopka joins Benzer's lab and discovers the period gene

intricate courtship rituals. In the 1960s, certain mutant Drosophila individuals were observed behaving in a strange way: they would court with both males and females but would not copulate, resulting in the mutant being named fruitless

A scientist who became fascinated by this fruitless mutant was Jeffrey Hall, an eccentric American who was known as a keen scholar of the American Civil War Jeff Hall worked with several researchers who had been Alfred Sturtevant’s students Hall initially was very interested in the period gene and he collaborated extensively with Michael Young’ s lab and both Hall and Young managed to isolate the gene Hall then collaborated with Michael Rosbash to understand how the period gene works. Hall Young and Rosbash all would go on to win the Nobel Prize in medicine in 2017 for their work on circadian rhythms

Another observation that Seymour Benzer had made in the 1960s was that Drosophila has a rudimentary ability to learn and remember. Benzer devised a screen to detect mutants that differed in their ability.

This takes us to the end of our exploration of behavioural genetics

It is clear that this field has made accessible a wide range of research topics and its potential has certainly not been fully fulfilled yet From understanding how organisms sense time, to how they fall in love to how they learn, all of what makes life so beautiful can be explored just by the power of genetics We are still the most complex system that we know of and I hope that I have revealed the magic lying in the biological sciences

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Obituary R & Konopka (1947) Leading Edge Cell, 181 https://doi org/10 1016/j cell 2015 03 038

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SHALLOW DIVE

Can CRISPR help save corals?

WRITTEN BY ASTRITI LAKSHMI ADITYA

EDITED BY ALEX EPSHTEIN

DESIGNED BY TAMARA YAP

Corals are organisms of great ecological importance and aesthetic appeal

Unfortunately, like many other organisms, they are in grave danger because of global warming Global warming leads to the heating of ocean waters, causing spread of infectious disease and oceanic acidification which makes corals more susceptible to death However, the most prominent reason for coral mortality is coral bleaching Coral bleaching is a phenomenon in which corals expel the algae living in their tissue in response to warming waters. Corals may survive the bleaching event but are more prone to death because this destroys their endosymbiotic relationship with

these photosynthetic algae providing them with essential nutrients in exchange for shelter and inorganic compounds Many studies have been conducted to understand the genetic basis of a coral’s response to stress but a recent breakthrough has been achieved using CRISPR

CRISPR-Cas9 is a powerful gene editing tool. CRISPR stands for ‘Clusters of Regularly Interspaced Short Palindromic Repeats’; it is a specialised stretch of DNA and Cas9 is an enzyme that acts as molecular scissors for cutting strands of DNA The CRISPR technology was adapted from the natural defence mechanism of bacteria CRISPR allowed bacteria to defend itself from viruses by

cutting the viral DNA and storing it in their own genome to prevent future attacks

In a study conducted by a team of scientists from Carnegie Institution of Science, the CRISPR-Cas9 technique was used to analyse a close relative of corals, the sea anemone or Aiptasia.

They identified a protein that activates genes relating to heat stress response, called Heat Shock Factor 1 (HSF1) In a following experiment to investigate the molecular basis of a corals’ response to heat stress, single-guide RNA/Cas9 ribonucleoprotein complexes were microinjected into fertilized eggs of Acropora millepora to produce detectable mutations in the HSF1 protein The mutated larvae survived at 27 degrees Celsius but at 34 degrees Celsius, they died rapidly whereas the wild type did not This indicated that HSF1 proteins play a role in the loss of heat tolerance of corals.

Further studies using the CRISPRCas9 technique for mutagenesis in corals targeting the HSF1 protein would help us understand what genes control the corals’ ability to adapt to external temperatures and how these genes function. Promising results in this field would enable the preservation of large coral reefs and the conservation of coral biodiversity

References

Cleves P A Krediet C J Lehnert E M Onishi M, & Pringle, J R (2020) Insights into coral bleaching under heat stress from analysis of gene expression in a sea anemone model system Proceedings of the National Academy of Sciences 117(46) 28906–28917

Cleves, P A, Tinoco, A I, Bradford, J, Perrin, D, Bay L K & Pringle J R (2020) Reduced thermal tolerance in a coral carrying CRISPRinduced mutations in the gene for a heatshock transcription factor Proceedings of the National Academy of Sciences, 117(46), 28899–28905

Lavars N (2020 December 22) CRISPR helps identify gene that regulates coral’s heat stress response New Atlas https://newatlascom/environment/crisprheat-shock-protein-dying-corals/

Image adapted from: medpagetodaycom

DNA metabarcoding: the future awaits an invasion

WRITTEN BY RISHA KAUR DUGGAL EDITED BY DRSHIKA MEHTANI DESIGNED BY TAMARA YAP

The most devastating loss, the loss of marine biodiversity has played havoc

with the environment, causing an imbalance at the molecular level (Pimm et al 2014) Although anthropogenic factors and climate changes indirectly affect this change, obsolete tracking techniques have proven to be inefficient in tabulating the biodiversity of a species The recent eDNA technique is divided into two methods through which evaluation of species takes place The methods are discussed below:

(i) eDNA barcoding - a method which is useful when one has to evaluate the single species of the fauna (Valentini et al , 2016)

(ii) eDNA metabarcodingestimating the sample without previous knowledge by using primers of the taxonomic group under consideration and integrating it with next generation sequencing (NSG).

Metabarcoding is a technical advancement through DNA sequencing which helps in taxonomic sequencing of species. There are several issues when it comes to assessing the population of the biodiversity DNA degradation during the polymerase chain reaction (PCR) amplification and sequencing is one of the most common issues along with false results with primer which were eliminated in samples using in silico, in vitro and in situ validation tests(Darling & Mahon 2011) . The primers would amplify closely related species such as Cyprinidae and Galidae, mistaking one for another For a variety of systems like the freshwater, marine etc, bony fish and the amphibians were analysed The unwavering quality and effectiveness of this new strategy was surveyed utilizing

in silico, in vitro and in situ approvals, which accentuated its qualities and constraints

Several benefits of the eDNA metabarcoding technique proposed right here make it an effective device for ecological research and aquatic biodiversity monitoring First, species detectability is shown to be superior to traditional surveys: the quantity of species detected in the use of eDNA was identical or better than conventional survey techniques in all instances for amphibians and in 89% of the cases for fish. Second, the monitoring effort required to infer the amphibian and fish communities is lower with the use of the eDNA method, permitting an increased tracking efficiency

Figure 1. A pictorial representation of next generation sequencing(NSG).

For instance, the fish sampling attempt required to reach an equal variety of detected species in lakes was 3 days the use of 88 gill nets vs 4 h the usage of the eDNA metabarcoding approach

Lastly, the primers are universal and can be used to estimate both the variety of bony fish and amphibians in the ecosystem.

References

The biodiversity of species and their rates of extinction distribution and protection Pimm S, Jenkins C, Abell R, Brooks T, Gittleman J, Joppa L, Raven P, Roberts C, Sexton J Science (2014) 344(6187)

Next-generation monitoring of aquatic biodiversity using environmental DNA metabarcoding

Valentini A Taberlet P Miaud C Civade R

Herder J, Thomsen P, Bellemain E, Besnard A, Coissac E Boyer F Gaboriaud C Jean P Poulet N, Roset N, Copp G, Geniez P, Pont D, Argillier C, Baudoin J, Peroux T, Crivelli A, Olivier A, Acqueberge M Le Brun M Møller P Willerslev

E, Dejean T

Molecular ecology (2016) 25(4) 929-942

From molecules to management: adopting DNA-based methods for monitoring biological invasions in aquatic environments

Darling J, Mahon A

Environmental research (2011) 111(7) 978-988

Figure 2 Results of the in silico validation of the ‘batra’ and ‘teleo’ primer pairs (A) sequence logo of the primer illustrating the quality of the match between the primer and its target sequence; (B) combined mismatch analysis of the forward and reverse primers (target group in green, nontarget group in red); and (C) length of the amplified fragment (excluding primers)

World hunger and malnutrition are back on the rise, after the slow but optimistic decline that has occurred for over a decade. Almost half of the deaths in children under five from low and middle-income countries are associated with undernutrition, putting them at a disadvantage when it comes to recovery time delays and mortality from infection According to the Hunger Map produced by the UN World Food Programme, 957 million people simply do not have enough to eat, and with the current pandemic, this number is estimated to increase The long-term effects of malnutrition are countless, including stunting of growth and increased risks of infections, diabetes and heart disease

The microbiome includes all the bacteria, archaea, viruses and fungi that reside in our bodies, hosting 5,000 different species There are over 10x the number of microbial cells in our gut compared to our body, weighing around 2kg. Due to its complexity and size, the microbiome is constantly referred to as a “second human genome ” , with many referring to it as a separate organ due to its vast range of functions including but not restricted to: drug, xenobiotic and host nutrient metabolism; maintaining the structure of the mucosal barrier; protection against pathogens; and providing energy from digested foods.

The gut microbiome is said to stabilize at around two to three years old and is similar to that of a fully developed adult. As a result, researchers hypothesize that if malnourishment occurs during this critical window, the microbiota will be negatively impacted and stunt both growth and development for life

A study by Jeffery Gordon in 2014 approached whether the distribution of the gut microbiota could cause malnutrition The 123 children aged 12-18 months with moderate acute malnutrition were given different supplements: half receiving the standard supplement whilst the other half included foods ranging from soy to peanuts, which had growing evidence that it could be used to increase the growth of age-appropriate microbes to repair the affected microbiome. The end result showed that malnourished children simply lacked beneficial gut microbes that continued to affect their bodily function and weight gain as they did not gain adequate weight for their ages, even after they were fed highly calorific foods designed for this purpose

Is the Malnutri Hands o Micro

Transplanting microbial samples from healthy and under-nourished infants into germ-free mice solidified the researcher’s findings The results from the mice perfectly mirrored those of the children: even though both groups were given the same foods, the malnourished children had underdeveloped microbiomes which lead to failure to gain weight and develop at the same rate as non-malnourished children Whilst gut bacteria transplantation has shown a good prognosis, it is not feasible in resource-scarce areas

The procedure requires anaerobic conditions for growth and culture, with storage being too expensive for the production of probiotics, which in recent studies have not provided optimistic results

Cure to tion in the of the Gut biome?

“Hidden hunger” is the terminology used for mineral deficiencies in populations with high levels of undernutrition Poor growth, birth defects, immune system disruptions and behavioural abnormalities all stem from zinc deficiencies (affecting an estimated 1 3 billion people) and iron deficiencies (affecting 2.3 billion) globally Studies by Tako et al at Cornell University have looked at the effects of biofortified foods on gut microbiota, such as iron-biofortified wheat, beans and zinc-fortified wheat The results showed a noticeable decrease in pathogenic gut bacteria and an increase in colonies that produce shortchain fatty acids, which are the main source of energy for the lining of the colon. This high concentration of short-chain fatty acids leads to an increase in uptake of minerals from the diet such as zinc and iron, which correlated with reduced risk of diseases such as Hepatitis B and bladder cancer

Microbiome targeted therapies are expected to be the way forward, with the goal to “repair” microbial immaturity with MDCF’s: Formulated Microbiome Directed Complementary Foods There is also research behind the use of specific strains of probiotics in preterm and low weight babies, with combinations of specific bacteria including Lactobacillus spp. and Bifidobacterium spp. The results from a study by Chen et al. on 118 children showed support for MDCF as a dietary supplement, as there was a change seen in levels of 70 plasma proteins (which include mediators for neurodevelopment and bone growth) and 21 related bacterial taxa which positively correlate with the weight-for-length z score, which is a measurement commonly used in healthcare to track a child’s development and nutritional status

We now know that the microbiome has been able to be manipulated and its plasticity towards environmental factors allows it to be targeted through various means. Personalised nutrition is ultimately the way forward, which involves looking at the variation in the gut microbiome, genetics and immunity Developing microbiome-directed foods that contain “biosimilar” ingredients readily available within each specific region will allow this to be affordable and accessible for all children to have the opportunity to thrive worldwide

WRITTEN BY CANSU OZDEMIR EDITED AND DESIGNED BY DORIS YU

References

Chen, R Y , Mostafa, I , Hibberd, M C , Das, S , Mahfuz, M , Naila, N N , Islam, M M , Huq, S , Alam M A Zaman M U Raman A S Webber

D Zhou C Sundaresan V Ahsan K Meier

M F , Barratt, M J , Ahmed, T and Gordon, J I (2021) A Microbiota-Directed Food

Intervention for Undernourished Children New England Journal of Medicine 384(16) pp 1517–1528

Christian V J Miller K R and Martindale R G (2020) Food Insecurity Malnutrition and the Microbiome Current Nutrition Reports, 9(4), pp 356–360

Iddrisu I Monteagudo-Mera A Poveda C Pyle S Shahzad M Andrews S and Walton

G E (2021) Malnutrition and Gut Microbiota in Children Nutrients, [online] 13(8), p 2727

Available at: https://www mdpi com/20726643/13/8/2727/htm [Accessed 26 Dec 2021]

Nations, U (2021) 2021 is going to be a bad year for world hunger [online] United Nations Available at: https://www un org/en/foodsystems-summit/news/2021-going-be-badyear-world-hunger

UNICEF (2017) Malnutrition in ChildrenUNICEF DATA [online] UNICEF DATA Available at:

https://data unicef org/topic/nutrition/malnutri tion/

Madhusoodanan, J (2021) Inner Workings: Can feeding the gut microbiome treat malnutrition? Proceedings of the National Academy of Sciences, 118(50), p e2120478118

Figure 1 2020 World Hunger Map produced by the UN's World Food Programme Countries are colour-coded based on the prevalence of undernourishment as a percentage of the total population

LGBT+ History Month

In a 2019 survey of more than 1,000 UK-based scientists, 32% of transgender and nonbinary scientists across all disciplines had experienced exclusionary, offensive or harassing behaviour at work.

Does Exercise Make Us Sick?

WRITTEN BY IRIS ZIELER

EDITED BY DRSHIKA MEHTANI DESIGNED BY ZAHRAA BHATTI

The relationship between exercise and immune function is one that concerns

us all as susceptibility to infection is a factor that dictates quality and length of life. Scientists are in agreement on the inverse relationship seen between amount of physical activity and susceptibility to disease. Nevertheless, a point of dispute in the scientific community is the immune system’s reaction to acute bouts of exercise, particularly endurance events For a long time, studies provided evidence to show reduced immune function following participation in strenuous exercise, such as Olympic games, marathons, and cycling races, basing their conclusions on the observation of reduced immune cell concentrations in plasma. However, recently Turner et al disputed these claims by providing a different viewpoint on the same data They argue that the reduced plasma immune cell concentrations are not proof of immune depression, but rather migration into peripheral tissues.

The idea that physical exercise substantiates our immune system stems from studies showing enhanced immunosurveillance and immunocompetence

In fact, Scheffer et al explained that regular moderate-intensity exercise directs the immune response to an anti-inflammatory status

While inflammation is very important to prevent, limit, and repair the damage induced by insult, chronic inflammation is the basis of chronic diseases such as Type 2 Diabetes Mellitus (T2DM), cardiovascular disease (CVD), as well as neurodegenerative diseases and cancers. Research has hence investigated the key neuroprotective effect, as well as the attenuation of developing and progression of chronic diseases from exercise The two main mechanisms modulating this are:

1 Enhanced immune function, reinforced antioxidative capacity, and increased energy generation efficiency, all of which reduce the susceptibility to inflammatory diseases

2 A heightened state of immunocompetence, driven by the

transient redistribution of immune cells to peripheral tissues – those exposed to pathogens - following exercise

Such effects are mediated by the exercise-induced down-regulation of microglia (macrophage-like immune cells of the central nervous system), nuclear factor NF-kB, and pro-inflammatory cytokines like TNF-ɑ, IFN-��, and IL-1ß, as well as the induction of anti-inflammatory mediators, such as IL-6 and IL-10 Normally, IL-6 is considered a proinflammatory cytokine, but studies have shown that skeletal musclederived IL-6 actually has antiinflammatory effects (Figure 1).

Immunosenscence describes the process of an ageing immune system It is characterised by a considerable shift in leukocyte concentrations, thereby increasing the susceptibility to illness with advancing age. Although ageing is inevitable, immunosenscence is not entirely predestined It is facilitated by lack of physical activity, low muscle mass, and poor nutritional status, meaning that more

athletic individuals are able to postpone and slow down ageing of their immune system. In fact, studies have shown that more active elderly have improved NK cell and neutrophil functioning, which is a sign of enhanced innate immunity Furthermore trained elderly have enhanced T-cell proliferation, meaning that they have a more potent adaptive immune capacity as well This is depicted in Figure 2, which outlines the differences in immune cell markers between active and sedentary elderly

Figure 1 Overview of the changes in immune markers and susceptibility to infection as a result of varying lifestyles

Figure 2. Role of regular physical activity in delaying immunosenescence, as indicated by immune cell abundance and function

For many years it has been accepted that acute bouts of exercise reduce our immune defence and increase susceptibility to infection This has been presented as the “open window” hypothesis, wherein the body is more prone to illness inflicted by opportunistic bacteria. However, in 2018, Campbell and Turner published a paper proposing the alternate view that, rather than immune suppression, we experience enhanced immune surveillance And that the commonly observed increase in upper respiratory tract infections (URTIs) among athletes following events, such as marathons, is driven by confounding factors.

Studies on post-exercise immune markers consistently show alterations in salivary IgA, NK cell and neutrophil function, and T and B lymphocyte function Until recently, the reductions in plasma levels of these effector molecules were regarded as a sign of reduced immune competence, thus increasing susceptibility to infection. Campbell and Turner countered this, by proposing that, rather than being evidence of immune suppression, decreased plasma levels could be an indicator of increased surveillance This would mean that these immune cells leave the plasma, to enter peripheral tissues that are more exposed to pathogens to protect the body from potential insult. They also pointed out that data on these markers is very susceptible to confounders, as demonstrated in the model they proposed (Figure 3) Here, they depict the various variables that are likely to play a role in the increased incidence of URTIs seen in athletes post-competition

These principles underline the wide array of extrinsic factors increasing the risk of infection, thus

establishing compelling arguments for their claim Raising awareness of these confounding factors, not only helped shape the more contemporary notion of immune potential surrounding acute bouts of exercise, but also helped influence generalised guidelines for both athletes and non-athletes attending competitions to minimise risk of infection.

Figure 3 (A-C) exposure to crowds, where spectators and coaches are also reporting higher occurrence of infection; (D) inter- and intra-individual differences in salivary IgA which is strongly influenced by oral hygiene and time of the day; (E) non-exercise factors, such as sleep quality psychological stress diet air travel jet-lag and environmental and a change in environmental conditions; as well as (F) the reduction in lymphocytes measured in the plasma not necessarily indicating reduced immune cells but rather redistribution of the latter

In conclusion, despite efforts to understand and measure immune function in relation to exercise, it is still a field of uncertainty

Epidemiological evidence allows us

to confidently say that in the longterm, regular physical activity enhances immune function, and prevents its degeneration with age Nevertheless, the acute impact of exercise is still an area of debate within the scientific community For many years it was accepted that bouts of strenuous exercise inhibit immune function, although this has recently been disputed by Campbell and Turner, who outlined an alternate way of interpreting the data As such, further research is required to draw firm conclusions on how the immune system is affected in the window immediately postexercise

References

Campbell J P , Turner J E (2018) Debunking the Myth of Exercise-Induced Immune Suppression; Redefining the Impact of Exercise on Immunological Health Across the Lifespan Frontiers in Immunology (9)

Gleeson, M , Walsh, N P , & British Association of Sport and Exercise Sciences (2012) The BASES expert statement on exercise, immunity, and infection Journal of sports sciences, 30(3), 321–324

Peake, J M , Neubauer, O , Walsh, N P , & Simpson, R J (2017) Recovery of the immune system after exercise Journal of applied physiology (Bethesda, Md : 1985) 122(5) 1077–1087

Scheffer D & Latini A (2020) Exerciseinduced immune system response: Antiinflammatory status on peripheral and central organs Biochimica et biophysica acta Molecular basis of disease, 1866(10), 165823

Simpson R J et al (2020) Can exercise affect immune function to increase susceptibility to infection? Exercise

Immunol Rev

Weyh, C , Krüger, K , & Strasser, B (2020)

Physical Activity and Diet Shape the Immune System during Aging Nutrients 12(3) 622

Mobility and Metastasis: Why can cancer cells move?

WRITTEN BY REBECCA HAMMERSLEY EDITED BY HUDA HAMMAD RATTU DESIGNED BY ZAHRAA BHATTI

Cancers are formed due to a deregulated cell cycle as a consequence of mutation

The cancer cells are no longer sensitive to the regulation of the cycle that is imposed at the R checkpoint So, they will continue through this checkpoint regardless of mutations These mutations can impact the cell in many ways; including metastasis Metastasis is when a cancer cell breaks away from its primary tumour and moves around the body causing a secondary tumour to form in a different area of the body

One of the mechanisms that fails to exist in cancer cells is anchorage dependence. This is when cells must be attached to a substratum in order to divide. This cell adhesion occurs due to contact dependent signalling Contact dependent signalling is a process where a specific signalling molecule is bound to the surface of the signalling cell and is then recognised by a cognate receptor on the target cell There are many forms of signalling receptors that can cause different outcomes e.g., the migratory cue of the plateletderived growth factor (PDGF). The signalling receptor PDGF has been linked to several types of epithelial cancers, like breast cancer, forms of lung cancer and glioblastoma

which is a form of brain tumour , and their tumour metastasis PDGF has also been implicated in the Epithelial-mesenchymal transition (EMT) in human breast cancer. EMT is a process whereby mesenchymal cells are created by carcinoma cells when their epithelial features are suppressed. This transformation allows for the mobility of tumours from their primary site thus allowing them to proliferate in a new site giving rise to a secondary tumour The overexpression of PDGF has been shown to be associated with tumour progression. This can partly be put down to the negative effects that PDGF has on anchorage dependence and adhesions within the mutated cancer cells

Density dependent inhibition, also known as contact inhibition, is another mechanism of the cell cycle that is inhibited in cancer cells. Density dependent inhibition is when the cells will divide until they cover the whole surface of the plate as a single layer of cells, once the cells come into contact with each other then division stops However, if you create a gap between these cells then the division will restart to fill it in. When this mechanism is disabled, it allows for cells to undergo uncontrolled growth leading to piles and clumps of them, thus forming a tumour of these

This image shows the process of metastasis in a mouse tumour Depicted in green are the tumour cells that have helped to reorganise the collagen into aligned fibres shown in blue These fibres provide the structural support for mobility which in turn helps the tumour cells to enter blood vessels (Red) thus eventually leading to the formation of metastases in other tissues

mutated cancer cells The prevention of cell proliferation by contact inhibition is signalled by membrane proteins and this process is mediated by higher levels of a cyclin-dependent kinase inhibitor, p27Kip1. This process is mediated by this inhibitor as it binds cyclin-CDK complexes, which are protein complexes that stop cells when they are in the G1 phase of the cell cycle It has been found that lower levels of p27 correlates to a poorer survival rate in cancer patients, thus highlighting the importance of contact inhibition in the suppression of tumours

These few examples barely touch the surface of the complicated system of the cell cycle, what can go wrong and how cancers can be formed. The formation and metastasis of cancers highlight the complexities of the human body and how the cells often successfully regulate themselves via multiple checkpoints in the cell cycle Yet when these mutations are allowed to slip through the checkpoints the damage they cause can be catastrophic

References

Liu Kun-Wei et al Platelet-Derived Growth Factor Signaling in Human Malignancies ” Chinese Journal of Cancer, vol 30, no 9, 1 Sept 2011, pp 581–584,

Ramos F S Wons L Cavalli I J and Ribeiro, E M S F , 2017 Epithelialmesenchymal transition in cancer: An overview Integr Cancer Sci Ther 4 pp 1-5

Carvalho, Inês, et al “Overexpression of Platelet-Derived Growth Factor Receptor α in Breast Cancer Is Associated with Tumour Progression ” Breast Cancer Research, vol 7, no 5, 1 Aug 2005

Farooqi, Ammad Ahmad, and Zahid H Siddik Platelet-Derived Growth Factor (PDGF) Signalling in Cancer: Rapidly Emerging Signalling Landscape ” Cell Biochemistry and Function, vol 33, no 5, July 2015 pp 257–265

Seluanov, A , et al “Hypersensitivity to Contact Inhibition Provides a Clue to Cancer Resistance of Naked Mole-Rat Proceedings of the National Academy of Sciences, vol 106, no 46, 26 Oct 2009, pp 19352–19357

Oudin Madeleine and Jeff Wyckoff Metastasis in a Mouse Tumour, news mit edu/2016/cancer-cells-remodelenvironment-metastasis-0315

Cows may hold the clue to ‘new-age’ antibodies

WRITTEN BY DRSHIKA MEHTANI

EDITED BY COURTNEY WEIR

DESIGNED BY TAMARA YAP

Bovines have adapted their immune systems to produce antibodies that feature an

ultralong heavy-chain complementary-determining region (CDRH3) CDRH3 is the variable region that targets antibodies to their respective antigens. These antibodies have a conserved anti-parallel β-ribbon ‘stalk’ that presents a disulphide stabilised ‘knob’ domain of 3-6 kDa It has been shown that when the knob domain is isolated from the parent antibody scaffold, it can function independently and bind to its antigen with high affinity. Thus far, the smallest, naturally occurring functional antibody domains that can work autonomously have been isolated from camelids and sharks and have heavy-chain variable region fragments of about 12-15 kDa (Figure 1) These small molecular weight knob domains offer a great advantage when it comes to developing new antibodies for antigens that are difficult to target

They can be developed to bind to antigens that are relatively smaller in size and difficult for conventional antibodies to bind to with high specificity Complement component C5 is one such target that researchers are trying to develop antibodies against

This development of an ultralong CDRH3 region is due the limited number of antigen gene segments in domesticated cattle The CDRH3 region is determined from DNA rearrangements of three types of gene segments: variable (V), diversity (D) and junctional (J)

Within the stockpile of bovine antibody heavy chain segments, cows have approximately 10X highly homologous VH, 10X DH and only 4X JH segments, giving a theoretical diversity of only 4,000 Humans by contrast have 55X highly homologous VH, 23X DH and 6X JH segments, giving a theoretical diversity of about 7 590. Cows have therefore found other ways to make more diverse antibodies to target a myriad of antigens By maximising somatic hypermutation (SHM) and developing an ultralong CDRH3 to increase the number of rearrangements within their limited immune gene subset, bovines have successfully increased their antibody diversity.

Bovine knob domains can be exploited and produced at a large scale to be used for the treatment of several inflammatory diseases Studies have been underway to target complement component C5 using knob domains isolated from bovine antibodies (Figure 2) C5 is a part of the complement cascade of the immune system and is a very important drug target because of its vital role in mediating chemotaxis. Targeting C5 is vital for effectively treating diseases with pathogenic complement dysregulation such as paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome

Figure 1 Molecular size comparison of therapeutic molecules ranging from the 50 kDa Adalimumab Fab fragment to the 0 45 kDa methotrexate A camelid repertoire derived antibody fragment (anti-lysozyme VHH) of molecular weight 15 kDa is also shown in comparison to a knob domain of molecular weight (4 2 kDa)

Targeting C5 has been very difficult due to its complex molecular structure. This issue could be overcome with the use of knob domains Future studies and clinical trials on the use of these knob domains can provide valuable insights into the development of new highly-specific antibodies and can provide potential treatments for diseases that present antigens that are relatively difficult to target.

References

Macpherson, A, et al (2021a) The Chemical Synthesis of Knob Domain Antibody Fragments ACS Chemical Biology 16(9) pp1757–1769

Macpherson A et al (2021b) The allosteric modulation of complement C5 by knob domain peptides eLife [online] 10 pe63586 Available at: https://pubmedncbinlmnihgov/33570492/ [Accessed 26 Dec 2021]

Macpherson, A, et al (2020) Isolation of antigenspecific, disulphide-rich knob domain peptides from bovine antibodies PLOS Biology 18(9) pe3000821

Wang, F, et al (2013) Reshaping Antibody Diversity Cell, [online] 153(6), pp1379–1393 Available at: https://wwwcellcom/fulltext/S00928674(13)00525-4 [Accessed 26 Dec 2021]

Figure 2. A schematic representation of the pathway to isolate knob domains from bovines

LGBT+ History Month

500 Queer Scientists

A visibility campaign for LGBTQ+ people and their allies working in STEM and STEM-supporting jobs — a group that collectively represents a powerful force of scientific progress and discovery.

uantumPercep t ion o f

WRITTEN BY ALEX EPSHTEIN

EDITED BY ANDREA MAZGALEVA

DESIGNED BY DORIS YU

Albert Einstein once said: ‘I like to think that the moon is still there, even if

I am not looking at it.’ This was in response to the contrasting studies of reality emerging in the field of quantum mechanics Experiments in the past have proven that particles spread out like waves, therefore sometimes seem to be in more than one place at once Hence, Einstein was pointing out that although objects can be in multiple places simultaneously, they only assume one particular position once we look at them This poses an important question: ‘Does anything actually exist when we are not looking at it?’

This can be further explored through the analogy of a tree falling in a forest If it falls, but no one was there to hear it, did the tree really make a sound?

There are multiple answers to this question, investigations lead to outcomes which surpassed the boundaries between the quantum and classical worlds, but probed the nature of reality itself The answer Einstein hoped for was one where objects exist whether or not we are looking at them

Together with his colleagues Boris Podolsky and Nathan Rosen, Einstein continued research into said question, coming up with a thought experiment in 1935, the purpose of which was to prove quantum mechanics an ‘incomplete theory of reality’ The experiment involved the theory of Entanglement, where a pair of particles were intrinsically connected, so whatever happens to one, also instantly affects the other

For example, the velocity or position of the first particle, will be identical to the second and

nt could be repeat the particles on opposite ends of the universe, meaning information being transmitted between the two particles is faster than the speed of light Einstein argues that this ‘spooky action at a distance’ was such a ridiculous concept that the outcome of any entanglement experiment has to be predetermined This leaves us with two options: either Einstein has to accept that quantum mechanics does not obey the laws of physics, or information breaks the ‘universal cosmic speed limit’.

The birth of quantum physics in the early 1900s, and its gain in popularity and research in the 1930s resulted in the discovery that light is made of tiny units of energy called quanta, now known as photons. Experiments such as Einstein’s that were conducted with single photons or particles of matter (eg electrons and neutrons) raised essential questions regarding the fundamental nature of reality Now, neuroscientists and philosophers also study these experiments in the context of human consciousness and how it influences the ontology of quantum universe as we know it.

Reverting back to Einstein’s experiment: measuring the entanglement of two particles, this can be scaled up to the entanglement of reality and consciousness, each constantly influencing each other, where one cannot exist without the other, and therefore cannot be isolated. This cannot be measured or quantified, yet is still explained by Einstein’s reflections regarding the moon, or the analogy of the fallen tree In other words, the universe and life are intertwined, where the universe cannot be explained in the absence of life and vice versa.

Hence, we can conclude that our outlook on reality is heavily influenced and shaped by our subjective experiences, but not entirely composed of them. Instead, consciousness is in a constant state of entanglement with the physical universe, where one cannot be explained or perceived without the other It is this relationship between subjective experience and the physical world that forms our perception of reality, also known as ’life’ .

References

Anil Ananthaswamy (2018, September 3) What Does Quantum Theory Actually Tell Us about Reality? Scientific American Blog Network

https://blogs scientificamerican com/obser vations/what-does-quantum-theoryactually-tell-us-about-reality/

Maldonado, C E , & Maldonado, C E (2018) Quantum physics and consciousness: a (strong) defense of panpsychism Trans/Form/Ação 41(SPE) 101–118 https://doi org/10 1590/01013173 2018 v41esp 07 p101

ALCOHOL AND HYPOGLYCEMIA: The Impact Of Alcohol on Glycemic Control and Insulin Action

WRITTEN BY ADELINA KRUSTEVA | EDITED BY ANOUCHKA AZRIA DESIGNED BY SAMARA SINGH

Doubtlessly, living with type 1 diabetes mellitus (T1DM) for over 10 years has played a

major role in my observation of alcohol impact on glycemic control and insulin action. With every alcohol consumption, I notice my blood glucose levels being significantly lower, my insulin sensitivity increased, which were often followed by hypoglycemia Seeing my hyperglycemic episodes diminished made me wonder how alcohol intake affects my blood glucose control and could it be a solution for decreasing high blood glucose levels?

Alcohol usage profoundly affects whole-body and tissue fuel metabolism, which expands the probability of morbidity and mortality in its consumers One of the various metabolic difficulties occurring with ethanol consumption is closely associated with glucose homeostasis. (Steiner, Crowell and Lang, 2015) Maintaining blood glucose concentrations at a steadystate level is crucial for survival due to the central importance of glucose as a source of energy for the brain and red blood cells (Bittar and Bittar, 1997) The whole-body glucose homeostasis is controlled by two hormones, insulin and glucagon

The first thing this article focuses on is the glucose rate of appearance (Ra) and glucose rate of disappearance (Rd) under the effects of alcohol It is well acknowledged that the pancreatic hormone glucagon is secreted in the postabsorptive state when glucose levels are low, promoting glycogenolysis and gluconeogenesis (Röder, Wu, Liu and Han, 2016) In experimental conditions, acute ethanol utilisation results in hypoglycemia on account of the profound decrease in glucose Ra accompanied by an elevated rate of Rd. These metabolic effects occur due to the oxidative metabolism of alcohol performed by alcohol dehydrogenase, which downsizes the pyruvate/lactate ratio by NADH/NAD+ ratio increment Thus, resulting in inhibition of gluconeogenesis and lowering circulating blood glucose levels (Figure 1) (Steiner, Crowell and Lang, 2015)

Several studies show that prolonged fasting with chronic alcohol consumption can lead to severe brain damage and persistent vegetative state evolving from acute hypoglycemia (Jain, 2002) Exceedingly, it has been suggested that glucose uptake by the brain

Figure 1. Ethanol is oxidized by the alcohol dehydrogenase to acetaldehyde This reaction produces one molecule of NADH Subsequently acetaldehyde dehydrogenase metabolises acetaldehyde to acetate producing another molecule of NADH The excess of NADH production resulting from ethanol consumption shifts the reaction equilibrium to the production of lactate inhibits the oxidation of lactate to pyruvate resulting in lactic acidosis Therefore there is not an adequate amount of pyruvate metabolized in the body to meet its demands which leads to inhibition of gluconeogenesis in the liver and hypoglycemia (Zakhari and Li, 2007,Forsander et al , 1965, Steiner, Crowell and Lang, 2015)

cells is diminished by alcohol intake This might be explained by the reduction of glucose transporter 1 (GLUT1) which leads to malfunction, neurological impairments and dysfunction of the blood-brain barrier (BBB) (Taghdiri, 2017)

The second discussion in this article is about the impact of alcohol on insulin action Many studies have shown that acute alcohol intoxication produces insulin resistance (Steiner, Crowell and Lang, 2015) On the contrary, a study by (Sierksma et al., 2004) shows that ethanol consumption has increased insulin sensitivity A variety of studies displays different outcomes for insulin action under alcohol intoxication However, it has been suggested that low to moderate drinking upraises and excessive alcohol consumption decreases insulin sensitivity (Taghdiri, 2017)

Predominantly alcohol consumption has similar effects on individuals with type 1 diabetes mellitus (TIDM). Acute alcohol drinking can lead to severe hypoglycemia as well as insulin resistance

However, the alcohol and insulin sensitivity relationship appears to be J-shaped, resulting in high insulin resistance in both heavy drinkers and abstainers (White, 2017)Therefore, ethanol intoxication does not help with hyperglycemia treatment but promotes the possibility of elevated HbA1c (glycosylated haemoglobin) levels resulting from the rebound high blood glucose levels in response to the hypoglycemia Supplementary, elevated insulin resistance stimulates hyperglycemia

References

Bittar, E and Bittar, N , 1997 Molecular and cellular endocrinology Greenwich: JAI Press

Forsander, O , Mäenpää, P , Salaspuro, M , Guthrie C and Hinton M 1965 Influence of Ethanol on the Lactate/Pyruvate and beta-Hydroxybutyrate/Acetoacetate Ratios in Rat Liver Experiments Acta Chemica Scandinavica 19 pp 1770-1771

Jain, H , 2002 Alcohol induced ketoacidosis, severe hypoglycemia and irreversible encephalopathy [online] Medical Science Monitor Available at: <https://www medscimonit com/abstract/in dex/idArt/4832> [Accessed 28 December 2021]

Röder, P , Wu, B , Liu, Y and Han, W , 2016 Pancreatic regulation of glucose homeostasis Experimental & Molecular Medicine 48(3) pp e219-e219

Sierksma, A , Patel, H , Ouchi, N , Kihara, S , Funahashi, T , Heine, R , Grobbee, D , Kluft, C and Hendriks H 2004 Effect of Moderate Alcohol Consumption on Adiponectin, Tumor Necrosis Factor-α, and Insulin Sensitivity Diabetes Care, 27(1), pp 184-189

Steiner, J , Crowell, K and Lang, C , 2015 Impact of Alcohol on Glycemic Control and Insulin Action Biomolecules, 5(4), pp 2223-2246

Taghdiri, S , 2017 Association of alcohol consumption with glucose homeostasis: a systematic review and meta-analysis White N 2017 Alcohol Use in Young Adults With Type 1 Diabetes Mellitus American Journal of Lifestyle Medicine, 11(6) pp 433-435

Zakhari, S and Li, T , 2007 Determinants of alcohol use and abuse: Impact of quantity and frequency patterns on liver disease

Hepatology 46(6) pp 2032-2039

LGBT+ History Month

“A professor once brought up my queerness in class as a deficit in my cognitive processing. One of my peers spoke up and said, “That is incredibly rude, disrespectful and inaccurate — and has no place here.” The professor tried to backtrack, but was also firm in his conviction that he was right."

-Kaela Singleton Postdoctoral researcher Emory University

Language & Epigenetics: Epigenetics Influence on Linguistics

WRITTEN BY MAHTA HAGHIGHAT GHAHFAROKHI

EDITED BY ALEX EPSHTEIN

DESIGNED BY ZAHRAA BHATTI

What is language? How has it come to exist as we know it, and use it today? Why is it, if at all. unique to humans? What does it show about who we are as individuals and as a species?

It is well known that language is unique to humans. Human language is distinct from all other forms of animal communications, which are often noticeably sophisticated, mesmerising and incredibly intelligent; yet not on par with the expressive power of human language

What then, makes human communication different? Human communication has allowed collaboration and expression of thought and creation of ideas that have crowned us the dominant species on the planet

The differentiating factor between human and animal communication is the human affinity to abstraction, embedded deeply in our genetic code. Other social animals are often capable of creating a wider range of sound signals, some beyond physical human limits Humans are capable of combining a limited range of words, in unlimited combinations Consider for instance the following phrases: 'let's eat grandma' vs

'let's eat! grandma.' A simple change can create a world of difference Humans share firstly the context, the shared abstract within which they can arrange words like pieces on a chess board, and secondly the words

Human communication, and thought process, is also the only known language to consider and make use of different tenses. No other animal is known to be able to consider the past and the future, to compose an endless number of sentences by combining and recombining words and different tenses, in order to tell a fictional or non-fictional story

Abstractive power of the human mind, more commonly known as imagination or creativity, is indeed what has given birth to human language If we were to consider a simplified history of language, it would be as follows: Drawings of stories, hunts, struggles, achievements, challenges, compassion, conflict, and what granted survival above all that were engraved in the environment humans inhabited, such as caves. Then came stories of gods and goddesses, myths and legends, figures of inspiration, obsession, distaste, and fear; with particular characteristics, some that one

must aspire to, and others to reject with all might From these ideas, the root of words These then formed conjugated forms

So what role does genetics play? The relationship between genetics and language remains for most parts a mystery. The most recent evidence however points at genetic predispositioning in infants and children that allow the acquisition of human language and abstractions

A study from Durham University explains that the peculiar expressive power of human language arises from creation and flexible architecting of sounds and signals in accordance with human psychology. A mathematical model was then used to explore the combinatory nature of human language The findings were somewhat endearing and perhaps paradoxical to mathematics used to discover them This model probed into the psychological mechanism and historical pathway behind such development, and found its ostensive nature required a socio-cognitive capacity and unity within a species. Language can therefore be described as an offspring of uniquely human innate values and curiosities

Two recent studies point at these uniquely innate human traits present from an early stage

The first study looks at the reaction of infants to language, only a few seconds after birth. Although not as comprehensive, the infant’s responses correspond to adult reaction to linguistic cues This included brain and neuroelectric activity In other words, the specific parts of the brain and neural patterns that were activated as a result of linguistic cues, previously thought to

be acquired when linguistics is learned at later stages of development Once again, it was the genetic blueprint in the infants that allowed them to respond, on a molecular level, to complex linguistic cues at such an early age, let alone much like an adult would

The second study is perhaps the most bizarre of them all To better understand how the result is discussed later in this piece, it may be worth considering the curious field of epigenetics and how we indirectly interact with our genes.

WHAT IS

EPIGENETICS?

Epigenetics in humans can be described as the dynamics between internal and external environment, genes and personification of an individual. External environment may consist of a collective of anything that results in any form of experience, such as sounds, food, images and sensation Internal environment is a collective inherited genetic predisposition and functionality, processes within the body, and hormonal and emotive responses to external environments that may be unique to an individual or common human trait The sum of the two translate into organic signals within the body that, in addition to molecular genetic build up, alter genomic characteristics, and observable physical properties of an organism These include the organism's appearance, development, and behavior These organic signals have shown to transfer between generations and play a role in evolution.

The second study, conducted at Pacific Lutheran University in Tacoma, showed that babies are listening to their mothers

talk during the last 10 weeks of pregnancy and at birth, they demonstrate what they’re heard Babies only hours old were able to differentiate between their native tongue and foreign languages This study was the first to reveal that language learning occurs in utero The investigation showed that this language learning influences the babies’ brain profoundly. The newly born babies showed differential actions and reactions once in an environment where language was used profusely and when interacting with other babies, their carers and siblings These behavioral patterns are thought to be a result of neuronal dynamics and genes that control mechanisms defining the identity of developing neurons in the brain and brainstem To reflect further, these behaviors are also a result of epigenetics

References

Christiansen, M H , Chater, N and Reali, F (2009) The biological and cultural foundations of language Communicative & Integrative Biology, [online] 2(3), pp 221–222 Available at: https://www ncbi nlm nih gov/pmc/articles/ PMC2717525/ [Accessed 30 Dec 2021]

Costa, D L , Yetter, N and DeSomer, H (2018) Intergenerational transmission of paternal trauma among US Civil War exPOWs Proceedings of the National Academy of Sciences, 115(44), pp 11215–11220

royalsociety org (n d ) Why is language unique to humans? | Royal Society [online] Available at: https://royalsociety org/news/2013/languag e-unique-humans/

ScienceDaily (n d ) How learning to talk is in the genes [online] Available at: https://www sciencedaily com/releases/201

4/09/140916112242 htm

The influence of genetics on language is undeniable Language has also shown to play a leading role in evolution The question however remains, whether language also influences genetics, not by altering molecular architecture of the genome, but by altering genomic expression via epigenetics, much like language affects how an individual expresses themselves and forms vital relationships

ScienceDaily (n d ) Language learning begins in utero study finds; Newborn memories of oohs and ahs heard in the womb [online] Available at: https://www sciencedaily com/releases/201

3/01/130102083615 htm [Accessed 30 Dec 2021]

The Atlantic (n d ) The Randomness of Language Evolution [online] Available at: https://amp theatlantic com/amp/article/54 4595/ [Accessed 30 Dec 2021]

LGBT+ History Month

Ben Barres

Professor at Stanford University

First openly transgender scientist elected to the US National Academy of Sciences

Xenobots - The Replicating Cellular Robots

WRITTEN BY VIDUR TANDON

EDITED BY MAHTA HAGHIGHAT GHAHFAROKHI DESIGNED BY ZAHRAA BHATTI

Neither fully robotic, nor a living organism, the so-called xenobots have recently been

synthesised out of biological material assisted by an evolutionary algorithm and are just a fraction of a millimetre wide When talking to the National Public Radio (NPR) about these new life-forms, Michael Levin, one of the scientists involved in their creation explains: ”The distinction between a robot and an organism is not nearly as sharp as we used to think it was, ” adding that ,”These creatures, they have properties of both."

The complicated procedure of creating xenobots begins with the building blocks, namely pluripotent stem cells, being extracted from blastula stage embryos of the African clawed frog Xenopus laevis, hence the name xenobots Prior to the assembly of the cells, an algorithm runs through numerous evolutionary

paths for the xenobot designs to gauge the most viable structures As seen in figure 1, out of the multiple designs in silico, the most ideal ones are selected and built in vivo using stem cells After observing their behaviour in comparison to what was predicted, the algorithm continues creating the most suitable 3D structure for the xenobots The assembly is done manually which also permits the addition of cardiac progenitor cells whose differentiation into cardiomyocytes creates contractile motion in the xenobots

Four main behavioural patterns were initially observed to subsequently modify and optimise the structures. Movement patterns, manipulation and transport of objects in the cellular environment as well as behaviour amongst each other, like docking to one another, played a role in creating the final structure of the xenobots. Towards the end of 2021, the authors of the first paper published another, describing the novel property of self-replication in the xenobots This is done using most of the four behavioural patterns described above Kinematic selfreplication, as it is being called,

occurs when the xenobots start collecting dissociated stem cells and creating aggregates which in turn form new xenobots. However, the spherical body shape is not optimal for this type of self-replication, in comparison to the adjusted and more suitable c-shaped body, as seen in figure 2, which was again found using the algorithm. Replication occurs over the span of approximately 5 days to a week, provided the conditions are suitable All this takes place without the presence of a nervous system or brain.

While scientific discoveries such as this are usually met with concern and hesitation the xenobots should not be a source of worry. Without the specific conditions in their petri dish, they are not able to survive, just as replication is not possible without a pool of stem cells, indicating that these organic robots can not escape the laboratory Concern regarding mutations in the xenobots is also unwarranted as no genetic material is exchanged between the offspring and their progenitor cells

Although xenobot technology is still at an early stage, there are hopes for it to be implemented in medicine and other scientific fields in the future, with hopes of the bots being able to travel through the body and assist with tasks such as removing plaque from blood vessels or finding cancer cells as well as collecting microplastics in the ocean In the coming years, other technological or biological advances may be inspired by the xenobots to advance these programmed balls of cells to solve some of science’s unsolvable issues.

Figure 1. The evolutionary algorithm runs through several evolutionary designs for the xenobots (A) The most robust designs are filtered (B) and then synthesised using the Xenopus laevis stem cells (C-F) Feedback is given to the algorithm which optimises the structures again (G) (Kriegman et al 2021)

Figure 2. In red a c-shaped xenobot creating another xenobot in green via kinematic selfreplication (Neuman, 2021)

References

Blackiston, D , Lederer, E , Kriegman, S , Garnier S Bongard J & Levin M (2021) A cellular platform for the development of synthetic living machines Science Robotics, 6(52)

https://doi org/10 1126/scirobotics abf1571

Hunt, K (2021) World’s first living robots can now reproduce, scientists say CNN

https://edition cnn com/2021/11/29/america

s/xenobots-self-replicating-robotsscn/index html

Kriegman, S , Blackiston, D , Levin, M , & Bongard J (2020) A scalable pipeline for designing reconfigurable organisms

Proceedings of the National Academy of Sciences, 117(4), 1853–1859

https://doi org/10 1073/pnas 1910837117

Kriegman, S , Blackiston, D , Levin, M , & Bongard, J (2021) Kinematic selfreplication in reconfigurable organisms

Proceedings of the National Academy of Sciences, 118(49)

https://doi org/10 1073/pnas 2112672118

Neuman S (2021) Living robots made in a lab have found a new way to self-replicate researchers say NPR

https://www npr org/2021/12/01/1060027395

/robots-xenobots-living-self-replicatingcopy?t=1640298759872

Sokol, J (2020) Meet the Xenobots, Virtual Creatures Brought to Life The New York Times

https://www nytimes com/2020/04/03/scie nce/xenobots-robots-frogs-xenopus html

Yeung J (2020) See the world’s first living, self-healing robots CNN

https://edition cnn com/2020/01/13/us/livin

g-robot-stem-cells-intl-hnk-scliscn/index html

LGBT+ History Month

“There is a big fear of what will happen when colleagues find out about your LGBT+ status, and it is really easy for that fear to grow in your own mind. But when you come out, you discover that there are one or two jerks out there. The majority will say, “Oh fine. What research do you do?” "

-Tom Welton Gay chemist Imperial College London

Are cyborgeyesthe visionofthe future?

The World Health Organisation (WHO) recently reported that a whopping 2 2 billion individuals are regarded as visually impaired or blind Of the mentioned, 253 million suffer from moderate to severe visual impairment (with visual acuity less than 30% than standard vision) and 36 million are deemed blind (with acuity less than 5%)

The pathway to solving a complex human condition… Scientists from around the world have been working on developing technological solutions to ultimately allow all those who are visually impaired to regain their lost eyesight Amongst the numerous studies performed, and advances within this field lies Argus II, a retinal prosthesis designed to provide accurate vision to those who are severely affected by a degenerative genetic disease characterised by the gradual loss of vision and effects every 1 in 3,500 ,

WRITTEN BY CHELSEA BLAIR

EDITED BY MUKA OFOMATA DESIGNED BY DORIS YU

Retinitis Pigmentosa (RP).

The prosthesis was curated by American company Second Sight and fights RP In France, IRIS II by Pixium Vision, is a bionic vision system utilising a subretinal implant which stimulates the damaged retina and provides compensation for the loss of vision of those suffering from retinal degeneration

The aforementioned implants constitute some of the major advances within this field, allowing patients to visualise numerous dayto-day objects and situations; from a door to a pedestrian crossing the street, to even distinguishing words written in a larger font Nonetheless, we are still quite far from developing an implant that renders vision perfect.

EC-Eye: the first completely bionic eye

It is for this reason that Hong Kong University of Science and Technology (HKUST), in collaboration with University of Berkeley California, have decided to carry out a research project with one goal at the forefront: to successfully create a bionic eye tailoring to all visual impairment - related conditions within the next five years EC-Eye (acronym for Electrochemical Eye”) is an electrochemical and biomimetic optic reproduced to mimic the exact structure and characteristics of the human eyeball The team of researchers have unveiled that the device differs considerably from other existing devices being it is a fully bionic eye rather than an implant targeting the retina Similar to our eyes, it measures slightly over 2 cm in diameter and functions by reason of a lens, retina, sensors and a nerve link

The prototype consists of nano sensors mimicking our photoreceptor cells embedded in a mock “membrane” composed of aluminium and tungsten, a metal extremely resistant to corrosion due to a protective film The retina is held in place by a silicone polymer support, with a lens and an artificial iris placed in front to mimic the function of the eyeball; the cavity is filled with an ionic liquid. To replace the optic nerve, which is an essential factor for transmitting data signals to and from our eye and brain, flexible nanocables are used to transmit said signals to a computer system The cables are made of a liquid metal and held in place by flexible rubber micro-sheaths As a whole, the prototype is binded together in a silicone polymer support.

Figure 1 Structure of EC-Eye HKUST

A functional capacity set to exceed our own?

Though the ocular prosthesis is still far from offering any remotely comparable sharpness to the human’s natural eye, its functioning capabilities are well underway So much so that Professor Zhiyong Fan of HKUST (leader of the project) is confident that their technology will improve to the point where the eye will not just replicate but surpass the performance of a human’s current globular organ function

The prototype’s current resolution is limited to 100 pixels- only enough to distinguish certain letters and shapes, and its field of vision rests at 100°, compared to the average 160° of our natural eyes In the future however, the prototype would essentially be able to capture images in a very low light at a comparably higher standard than the human eye, and in time, offer an overall better performance The reason being is that the 10 million cells of the human eye cannot even begin to compete with the 460 million nano-sensors the prototype is able to integrate, which would at length permit the bionic prototype to receive light signals at a quicker pace and display images at a higher resolution Researchers would like to eventually connect perovskite nanowires (photodetectors) to the nerves of their visually impaired patients, allowing them to regain full sight

Thus, the bionic eye is a prominent step forward and a great hope for those suffering from visual blindness While there are still many daunting challenges that remain unsolved, Zhiyong and his team’s research is well underway Perhaps ocular prosthesis can eventually expand onwards to face future innovations concerning robotics and medicine? The possibilities with human organ replication are enticing and therefore virtually endless

References:

A breakthrough bionic eye might one day give us night vision (2020, June 10) South China Morning Post https://www scmp com/abacus/tech/artic le/3088289/breakthrough-bionic-eyemight-one-day-give-us-night-vision

EC Eye bionic eye: better than the real thing? (n d ) EYESEEMAG Retrieved December 17 2021 from https://eye-seemag com/en/high-tech/the-ec-bioniceye/

HKUST Scientists Develop World’s First Spherical Artificial Eye with 3D Retina | The Hong Kong University of Science and Technology (n d ) Hkust edu hk

Retrieved December 17 2021 from https://hkust edu hk/news/research-andinnovation/hkust-scientists-developworlds-first-spherical-artificial-eye-3d

Structure of EC Eye (n d ) EurekAlert! Retrieved December 17, 2021, from https://www eurekalert org/multimedia/6

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MR-guided focused ultrasound: paving the future for brain cancer treatment

WRITTEN BY VENUS HO

EDITED BY ZAHRAA BHATTI

DESIGNED BY ZAHRAA BHATTI

Ahuge range of drugs have been designed in targeting neurogdegenerative diseases

and cancer, yet one of the obstacles that significantly impact their efficacy is the presence of the blood brain barrier Small and lipid soluble molecules are capable of moving across the blood brain barrier, but most drugs that are relatively large and lipid-insoluble are incapable to do so Nevertheless, there is a possibility that this hurdle might be able to be overcome by a new medical solution - Magnetic resonance-guided focused ultrasound (MRgFUS).

What is the blood brain barrier?

The blood brain barrier is a necessary structure in preventing the entry of harmful substances such as toxins, bacteria, and viruses, via blood vessels, into the brain In a typical blood vessel, gaps are present within endothelial cells, allowing biomaterial to pass through. On the other hand, the endothelial cells that form the blood brain barrier are tightly sealed This increases the difficulty for the diffusion of blood borne substances, thus serving its purpose for the regulation of homeostasis in the

central nervous system (CNS) However, its performance also ends up as a conundrum for therapeutical drugs to pass through and act on the brain tumour.

unnecessary damage to neighbour tissues When tissues absorb ultrasound, heat energy generated results in necrosis and protein denaturation.

Mechanism of MRgFUS

MRgFUS targets the pathology of brain diseases via two different pathways: increasing the permeability of the blood brain barrier and eradicating brain tumours by ultrasound-induced heat. This medical technique is the combination of two technologies –Magnetic resonance (MR) and ultrasound. The former has always been used for imaging, thus aiding surgeons in treatment planning with greater accuracy While the latter is an acoustic energy form that penetrates through a range of tissues, for example, muscle, skin, and fat to name just a few The fusion of both techniques further pinpoints the energy waves to the desired site of action without posing

The injection of microbubbles is also accompanied by the use of MRgFUS. Despite the common perception of bubbles in blood as a medical emergency, it has been developed as a means to transport therapeutic drugs in recent years Positive results were shown when the drug was incorporated within the bubble via chemical bonds and introduced to human organs (Stride E et al, 2015) This increases the efficacy of the drug by enhancing the delivery of molecules After the introduction of ultrasounds, focused ultrasound is directed into the brain through the skull non-invasively This promotes the activation of microbubbles, which oscillates and causes minor disruptions to the blood vessel The site where ultrasound is applied can then enable drugs to pass through the blood brain barrier within a 24-hour gateway

Although some brain tumours can be removed directly with surgical procedures, the spread of the invasive cells may render these methods impossible, due to the imposition of potential harm to patients during operation. To deliver selective treatment, MRgFUS brings promising results by transporting drugs directly to affected regions

Its feasibility had been examined in animal models in the recent decade In a mouse model (M Kinoshita, N McDannold et al , 2006), there is an

This image depicts the cell types within the neurovascular unit of the blood brain barrier, labelled with tight junctions (TJ), pericytes (PC) endothelial cell (EC) and astrocyte endfeet (AE)

implication that the concentration of Herceptin in the targeted tissue increases with the increasing power of MRgFUS. It has recently progressed to the first human trial, where Herceptin, a monoclonal antibody, was introduced into four breast cancer female patients, with the implementation of the new technique (Yiu Meng, Raymond M Reilly et al , 2021) Results have shown that the cancer tumours decreased in size and display greater drug delivery efficiency compared to non-targeted lesions, without imposing any negative impact on patients’ safety

Current applications of MRgFUS

The current applications of MRgFUS include treating essential tremor and tremor-dominant Parkinson’s disease High temperature is applied to a certain spot on the thalamus, where its abnormality is responsible for the tremor symptoms of these diseases

The consideration of implementing such a procedure in cancer treatment is further supported by its benefits in terms of treatment delivery. Unlike conventional radiological cancer treatment, radiation complications are significantly lower for MRgFUS Unnecessary incision and hence decreased risk of infection from equipment providing its noninvasive feature This also offers greater precision and accuracy, limiting toxicity to brain tumours, minimising injury to normal tissues.

Not only does this MRgFUS expands the gap within the blood brain barrier, but also paved a new pathway for neurological therapeutics. Although the recent first-in-human trial has delivered promising results for this technique, more clinical data are required to further assess its effects and safety in the long run Nonetheless, the possibility of making MRgFUS available to doctors for cancer treatment is a prospect to behold.

References

M Kinoshita N McDannold (2015) The blood-brain barrier Cold Spring Harb Perspect Biol 2015 Jan 5;7(1):a020412 doi: 10 1101/cshperspect a020412

PMID: 25561720

https://www ncbi nlm nih gov/pmc/articles/ PMC4292164/

M Kinoshita, N McDannold, F A Jolesz, K Hynynen (2006) Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasoundinduced blood-brain barrier disruption Proc Natl Acad Sci U S A 103 11719–11723

https://www pnas org/content/103/31/11719 l ong

Jung NY et al J Korean Med Sci (2018) Magnetic Resonance-Guided Focused Ultrasound in Neurosurgery: Taking Lessons from the Past to Inform the Future

PMID: 30369860

https://www ncbi nlm nih gov/pmc/articles/ PMC6200905/

McEwan C Owen J Stride E Fowley C Nesbitt H Cochrane D Coussios CC Borden M, Nomikou N, McHale AP, Callan JF (2015) Oxygen carrying microbubbles for enhanced sonodynamic therapy of hypoxic tumours J Control Release 2015 Apr 10;203:51-6 doi: 10 1016/j jconrel 2015 02 004 Epub 2015

Feb 4 PMID: 25660073

https://www sciencedirect com/science/arti cle/abs/pii/S0168365915000942?

via%3Dihub

Yiu Meng Raymond M Reilly Rossanna

C Pezo, Maureen Trudeau, Arjun Sahgal, Amit Singnurkar, James Perry, Sten

Myrehaug, Christopher B Pople, Benjamin Davidson Ma-Heleth Llinas Chinthaka

Hyen, Yuexi Huang, Clement Hamani, Suganth Suppiah, Kullervo Hynynen, Nir

Lipsman (2021) MR-guided focused ultrasound enhances delivery of trastuzumab to Her2-positive brain metastases

Science Translational Medicine

13 Oct

2021 • Vol 13 Issue 615 • DOI: 10 1126/scitranslmed abj4011

Love on the Brain: The Neuropsychological Basis Behind Love, Lust, Attraction and Companionship

WRITTEN BY ZARA NELSON

EDITED BY MAYA ROWLEY DESIGNED BY CELESTE COCKMARTIN

Love is a feeling that people across the globe live, die and kill for

Despite being consistently described as an immediately identifiable feeling, it may come as a surprise that science still knows little about the complex emotion of love.

As far back as the ancient Greeks, love has been closely tied to the heart and its associated symbol The 7th-century poet Sappho wrote of the effect of love on her heart, the subjects being female disciples living on her island Lesbos She wrote, ‘love shook my heart, Like the wind on the mountain Troubling the oak-trees ’

Although the symbol for the heart bears almost no resemblance to the beating ball of flesh inside our chest, it’s easy to understand why this connection was made once upon a time. The ancient Greeks were right in linking love to something deeply biological (the heart), however missed the mark on which organ is responsible Instead, neuroscience, social anthropology and psychology have shown the brain plays the biggest role in human love

According to scientists, what we do know is that three concepts form the basis of romantic love: Lust, Attraction and Attachment Each of these is said to be distinct but have some overlaps, with different chemicals and brain systems at play.

Lust

Lust can be defined as the desire for sexual gratification and may be an early factor in the phasic development of romantic love Lust, closely linked to sex drive or libido, is evolutionarily advantageous, its outcome is reproduction and therefore it drives the survival of our species The hypothalamus is a key player in the sex drive as it triggers the testes and ovaries to produce the hormones testosterone and oestrogen. Despite the labelling of these as ‘male’ or ‘female’, they are not sex-specific Testosterone, for instance, is known to increase libido in all Oestrogen has fewer but still observable effects on lust; some women report higher libido during ovulation when oestrogen levels in the menstrual cycle are at a high It can be assumed that the hypothalamus constitutes solely the erotic component of love, as feelings of maternal love do not activate this structure in the same way that sexual arousal does.

The current research landscape on sexual arousal and lust has centred on the cis-male sexual experience, however, some contemporary evidence offers a novel role for gender identity and biological sex in sexual arousal One study showed that transgender men followed different patterns of sexual arousal than cis-gendered men, while cisgendered women were found to be sexually aroused by both males and females no matter their sexual orientation. Therefore, we know that hormones alone do not drive sexual arousal in humans

Attraction

Attraction, the next key factor in understanding love, is related to the concept of sexual desire but the two are not mutually exclusive Ultimately, lust can occur in the absence of attraction or vice versa If you will, attraction may be likened to a distant cousin of sexual desire, in the family tree of romantic love '

Biologically, Attraction is more accurately described as a brain system rather than a feeling or emotion, one that is closely associated with dopaminergic reward systems in mammals The ‘feel good’ hormone dopamine is the currency of this system It is released in high quantities during attraction to another person, as well as when partaking in activities that invoke pleasure or positive emotions. Release might be triggered by spending time with loved ones, sexual intercourse or even listening to music. Fisher et al. showed that when presented with images of a beloved, fMRI scans of 17 people who were “intensely in love” showed activity specifically in the right ventral tegmental region (VTA) and the caudate nucleus It is no coincidence that these areas are rich in dopamine and linked to motivation and reward

Some argue that most human traits can be distilled down to evolutionary adaptations, the mechanism of attraction included Social anthropologists have suggested that monogamy, or attraction to specific individuals, evolved as a time and energy-saving mechanism which speeds up the reproductive process and increase its efficiency Developing an attraction to one individual allows us to focus all of our energy and mating strategies on one person, hence maximising offspring production In other words, we have better chances of success ‘putting all of our eggs in one basket’

Attachment

Scientists theorise that Attachment is what makes love last, with the hormones oxytocin and vasopressin at its epicentre. Some may be more familiar with oxytocin as the ‘cuddle hormone’, as it modulates motherchild bonding, and is released during childbirth and breastfeeding. What makes attachment unique is its versatility, it can take the form of not only romantic love, but in friendship or the bond between a mother and child. With regards to romantic love, oxytocin plays a significant role in sexual intercourse

Synthesised in the hypothalamus, it is released into the blood from the pituitary gland in particularly high levels in both men and women during orgasm In combination, these hormones act in the phase of romantic attachment in relationships to develop a attachment bond through sexual intercourse

It is long known that there is a strong visual component at play in the experience or development of love Evidence shows that both viewing a picture of a loved one and male ejaculation has been found to deactivate the amygdala Given that this region functions during stressful situations, its deactivation suggests an induced comfortable state and mitigation of fearful emotions

Additionally, the formation of an attachment between one and their partner is confirmed by observations of the prefrontal cortex, parietotemporal junction and temporal lobes Within these areas are zones that allow the brain to distinguish itself and its set of beliefs from others Such areas are inactivated when in love, rendering the brain less proficient in its capacity to separate one from its partner. Essentially considering the two to be one mind The complete ‘unity’ often associated with true love in literature may be more accurate than once thought, in the context of a bond between partners

Possibly the most astonishing feature of love is its ability to modulate over time. Fisher found that the brains of people in longerterm relationships lit up in the ventral palladium region during MRI, an area known to coordinate attachment behaviours. We now know that romantic love changes over time, with attachment supplementing the stability of a relationship Evolutionarily, this might also motivate parenting behaviours

A Double Edged Sword

It is without a doubt that love evokes happiness, pleasure and closeness, which in turn facilitate our survival from birth to death Romantic love is also said to be a universal craving, analysis suggests almost 100% of humans experience love at some point in their lives. Research highlights the ugly side of love, an addiction with numbers of affected individuals surpassing that of substance abuse, or gambling At its height, love is an obsessive state of euphoria, and at its worst, it emanates into depression, murder or suicide for some Are we viewing love through rose tinted glasses? Whilst considering the positive implications of love, we must be wary of romanticising the effects of romance

To this end, it is not startling that the brain in love looks very similar to the brain on cocaine Evidence shows dopamine rich regions in the brain that are stimulated by romantic feelings are the same regions active when opioid drugs such as cocaine are released into the nervous system Unfortunately, an increase in dopamine comes hand in hand with a decrease in serotonin, a crucial regulator of mood and appetite control The depletion of serotonin in individuals who are in love experiences what is comparable to that of patients with obsessivecompulsive disorders

Furthermore, overlapping reward systems and areas rich in oxytocin or vasopressin receptors actually deactivate regions that are associated with negative emotions and social or moral judgement

In these areas assessment of other people's intentions and emotions takes place, their deactivation induces a brain fog where judgement of our partner is suspended In the eyes of those in love, their partner can do no wrong, validating the concept of being ‘blinded by love We can understand why such blindness might have damaging implications

Love is so often tied to exhilaration, euphoria and joy that we forget the full range of its consequences, including the negative Ultimately, love has been the muse of countless artists, poets, musicians, and authors since time began. Many of whom have stipulated that love is allencompassing, euphoric and blinding, even addicting, dangerous, obsessive and maddening Although each individual should form their own interpretation of love, science has suggested that when boiled down to the chemicals, these artists may have been correct all along

References

Benson, E (2003, April) Sex: The science of sexual arousal Https://Www apa org https://www apa org/monitor/apr03/arousal

Fisher, H , Aron, A , & Brown, L L (2005) Romantic love: An fMRI study of a neural mechanism for mate choice The Journal of Comparative Neurology, 493(1), 58–62 https://doi org/10 1002/cne 20772

Raines J Holmes L Watts-Overall T M Slettevold, E , Gruia, D C , Orbell, S , & Rieger, G (2021) Patterns of Genital Sexual Arousal in Transgender Men Psychological Science 32(4) 485–495 https://doi org/10 1177/0956797620971654

Zeki, S (2007) The neurobiology of love

FEBS Letters 581(14) 2575–2579

https://doi org/10 1016/j febslet 2007 03 094

Neuropsychology of Art Visualisation

WRITTEN BY ANNIKA ROBIOLIO EDITED BY JABARI LAMBERT DESIGNED BY CELESTE COCKMARTIN

Imagine yourself looking at Monet’s expansive water lily or the deep colours of a Rothko painting Do any of these get your attention?

Do they evoke amazement, happiness or incredible sadness?

Maybe you see someone else ecstatic in front of a painting which instead transmits no feeling to you

But what is it that our brain “ sees ” in front of art?

Through our eyes, we receive incomplete information about the external world which is completed and processed in our brain. This visual perception process is called the “beholder’s share” and it mainly focuses on discovering what is present in an image and where it is located. The information is captured through the eye and is processed by the optic nerve before being directed to the lateral geniculate nucleus. Here the information is split, the image identification is processed in the hippocampus, our memory centre that works through image association The spatial information is processed through superior pathways, from the primary visual cortex to the top of the brain, linked with motion and depth

Certain paintings stimulate your emotions, leading to long periods of time spent trying to read their mysteries and symbolic content The consequent emotion-feeling process may be linked to your initial attraction towards that particular artwork and discovering the emotions that the artist wanted to transmit, adding them to your privately perceived meanings deciphered from the shapes and colours of the canvas Art relies on eliciting aesthetic-related responses as our attention is caught by what we perceive as attractive or interesting Our brain seeks attraction in order to elicit pleasure responses, which culminate in the release of neurotransmitters such as dopamine through reward-pathways in our brain These pathways, which are linked with our memory, store information about pleasurable experiences, inducing us to seek out these experiences again in order to relive that pleasure

Initially, scientists believed that attraction was linked only with the pleasure centre in the hippocampus and the aforementioned rewardpathway in the medial forebrain bundle and ventral tegmental area However, now other areas of the brain, like the orbitofrontal cortex regions and the limbic system, are thought to be involved. Could this network amplification implicate a wider pathway with other neurotransmitters and hormones that influence our attraction responses in different areas of the brain?

To understand the preference basis of the beholder's share a new field has grown, Neuroaesthetics. Involving the use of fMRIs, blood flow is measured in the brain to evaluate its activity and to study the biological basis of aesthetics It might seem paradoxical to try to scientifically evaluate emotions, attraction and creativity that are part of the aesthetic experience, but we have to think about it not as trying to describe the subjective impression, but only to quantify measurable brain responses

The study of aesthetic visualisation can lead to questions related with artistic production, which seem to be more complex to answer What could be the mechanisms behind creative production? Take improvisation You may have wondered about a musician's thought process while improvising, if there is any reason behind the melodies he creates or if the note combination just flows through him or her Our movements are mainly controlled by the decision-making and judgement pathway in the lateral prefrontal cortex and, through fMRI studies on musical improvisation, a diminished pathway activity in this cortical area was noticed. This suggests that in order to improvise we need to disengage from our judgement and decisionmaking abilities In contrast, we largely observe activation of the medial prefrontal cortex, which organises our memories and internal states, consisting of our private emotions, thoughts, interactions and moods. Without the judgementpathway, it is thought that the brain can focus on multiple internal states simultaneously Could this be the basis of creativity? We don’t have to think of this as a completely blind process, because creativity is also guided by the artists’ so-called “selective-retention”, which is the observation that we do have control of which of our ideas we amplify, and which we erase

Both artistic production and visualisation could therefore rely on the new association of these multiple internal states

While creating art we may be more captivated by certain thought associations, and these are the ones that we will try to express Perhaps, in the same way, we feel compelled to decode art whose aesthetics strike a chord with our private internal states and feelings It could be said that a good explanation of what motivation we have to experience art is that in doing so we attempt to reconstruct the artistic creation processes in our brain This might be the reason why we feel so engaged and connected to a certain piece

However, our mind does not stop there when analysing aesthetic meaning. We apply an additional process when we look at someone ’ s painting Especially with portraits, there is a need to interpret the artist's thoughts, guess his intentions, aspirations and ideas We perceive them as independent from our own

Works of visual art can be symbolically organised, even when spatially disorganised representations of reality They are storytellers which evaluate our imaginative capacities, and that throughout time have been essential to solving problems in our imagination and communicating personal realities to others, linking higher thoughts with primal emotions In the end, our curiosity towards art could derive from an internal urge to recreate the cognitions and emotions of a creative process, and shape it as our own In this way, an artistic process does not end with a completed canvas, but continues in the mind of the viewer, making it a common ground for us to try to make sense of the complexity of our emotions, as we see an opening into other’s thoughts, which imperfectly mirror our own

References

E R Kandel 2016 “Reductionism in art and brain science” Columbia University Press

E R Kandel 2012 “The age of insight” Random House

Zaidel D W (2010) Art and brain: insights from neuropsychology biology and evolution Journal of anatomy, 216(2), 177–183

C Sherman 2014 Visualizing art The Dana Foundation

A Reynolds “Behind the mind and psychology of art work Ren Creative Works

Why do we have a folded cortex?

WRITTEN BY LAVINIA KADAR EDITED BY DRSHIKA MEHTANI DESIGNED BY TAMARA YAP

When looking at a human brain, one feature that stands out immediately is

its highly folded surface Why is this surface layer, called the cortex, thrown into so many folds? What is the purpose behind those folds, how do they arise and what happens when folding goes wrong?

Folding can be useful in that it allows a large surface area to be accommodated into a limited space This could be a main reason why our cortex is folded, to fit its large surface area into the skull However, this doesn’t yet explain why the specific location of the folds between brains of different people is very similar. And why hasn’t nature chosen to increase the size of the brain and skull after birth to accommodate for the larger surface area? If that was the case, it seems that we would not need folding in the first place Interestingly, the folds in human brains are arranged with gaps and spaces If neurons were packed together without those spaces, we could have had a smooth brain without even reducing the number of neurons.

This implies that folding does not only allow a large surface area to fit into a limited skull, but also that the specific folding pattern might have an important functional role This would also align with the observation that the largest folds often separate areas of the cortex with very distinct functions For example, one of the main folds called the “central sulcus” separates the motor area from the sensory area.

A common approach to get insight into why something is a certain way is to look at what happens when it goes wrong. Lissencephaly is a condition in which individuals have less folding than the average brain Equally, in polymicrogyria individuals have an increased amount of folding Interestingly though, both conditions result in symptoms such as seizures, problems with swallowing, muscle spasms and retardation of various kinds. Since both more and less folding result in similar symptoms, determining the functional role of having a folded cortex is very challenging.

When comparing the brains of different mammals, we see different degrees of folding For example, dolphins have a highly folded brain, even more folded than humans In contrast, mice and rats have smooth brains All mammalian species, evolutionary speaking, originate from a common ancestor. This ancestor is thought to have had a folded cortex too, so some species must have lost this folding while others preserved it Folding the brain’s surface without a doubt represents an immense effort in development Thus, there must have been evolutionary advantages for us as a species to keep our cortex folded, while other species did not

We might come closer to understanding why the cortex folds by looking at how it folds What drives the folding process biomechanically speaking? Different characteristics have been observed for the different layers of the developing brain. For example, it has been found that the degrees of thickness and elasticity vary from one layer to another It has also been observed that the outer cortical layer grows faster than the inner layers of the brain With those observations, we can make models simulating the folding process of the brain

When the brain is modelled by making a gel structure with a thin surface layer (representing the cortex) that grows faster than the more voluminous inner layers, folds can be created that look very similar to the folds in actual brains Interestingly, this happens even without the physical constraint of the skull. However, the specific location of the main folds can not be consistently recreated this way There thus seem to be additional cellular processes involved that contribute to determining the exact folding pattern

All in all, the folds on our brain’s surface are thought to arise primarily to allow the large surface area to fit into the proportionally small skull The folds are also thought to have functional importance but specific functions are difficult to determine, because very similar symptoms arise in disorders of both too much and too little folding The different growth rates of the cortex and inner layers of the brain are sufficient to generate folds, however, how the specific locations of folds are determined is not yet fully understood.

Figure 1. Pictures of gel brain models at different time points, adapted from Tallinen et al , 2016 The authors created the models by filling gel into 3D moulds, made using human fetal MRI scans They then covered those models in a thin layer of a second gel When immersed in solvent, the thin outer layer, representing the cortex, swelled, simulating an increased growth rate of the outer layer in relation to the inner layers.

References

Kattuoa M l and Das J M (2021) Lissencephaly [online] Nih gov Available at:

https://www ncbi nlm nih gov/books/NBK56 0766/ [Accessed 7 Dec 2021]

Stutterd, C A , Dobyns, W B , Jansen, A , Ghayda Mirzaa and Leventer, R J (2018) Polymicrogyria Overview [online] Nih gov Available at:

https://www ncbi nlm nih gov/books/NBK13 29/ [Accessed 7 Dec 2021]

Kelava I Lewitus E & Huttner W B (2013) The secondary loss of gyrencephaly as an example of evolutionary phenotypical reversal Frontiers in neuroanatomy 7 16

Tallinen T Chung J Y Rousseau F Girard, N , Lefèvre, J , & Mahadevan, L (2016) On the growth and form of cortical convolutions Nature Physics 12(6) 588593

Bayly, P V , Okamoto, R J , Xu, G , Shi, Y , & Taber, L A (2013) A cortical folding model incorporating stress-dependent growth explains gyral wavelengths and stress patterns in the developing brain Physical biology, 10(1), 016005

Kroenke, C D , & Bayly, P V (2018) How forces fold the cerebral cortex Journal of Neuroscience 38(4) 767-775

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