ScienceMind Winter 2023 (Issue 14)

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Is your heart giving you migranes? pg. 01

The blood test that can help diagnose Alzheimer's pg. 15

Pee Power: Could urea fuel be the future of sustainable energy? pg. 23

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DearReader,

Welcome to our Winter 2023 issue! This issue has articles in the categories of cardiology, neuroscience, medicine, pharmacology, business/law, technology, chemistry, and biology. We also present a special interview with Professors Martin Giurfa and Albert Cardona, who take us on an insightful journey into the mindofaninsect.

At ScienceMind, we strive to keep informed on the latest developments in STEM. Hence, we couldn’t help but notice the attention surrounding generative AI and the impact it’s already making on all aspects of humanity. In an effort to embrace this new and powerful technology, our editorial team has decided to letOpenAItaketheleadindesigningourcover!

Moreover, we have exciting news! The articles in this issue will decide the winners of the first-ever ScienceMind Awards. Make sure to sign up to our mailing list and stay tuned on social media for more information regarding nominations,voting,andofcourse,theawardsparty!

If this is your first time reading our magazine...

ScienceMind is the award-winning, student-led science magazine of King's College London. We report the latest findings in STEM to students and the wider community. We showcase and develop the written and oral communication skills of students interested in STEM by concisely explaining complex scientific concepts in the form of lay articles and by conducting interviews. Authors can also broaden their knowledge by writing articles for differentsectorsbetweenissues.

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The Deputy Editor-in-Chief

Olivera Mitevska

ISSUE14|2023
CARDIOLOGY
your heart giving you migraines? NEUROSCIENCE Universe 25: Can the growth and demise of rats predict human nature?
is it like to be an insect? MEDICINE
blood test that can help diagnose Alzheimer's PHARMACOLOGY Poppies to Pills: The development of synthetic opioids BUSINESS/LAW The Great Unequaliser: How COVID-19 Made Health Disparities Worse in the UK TECHNOLOGY Pee Power: Could urea fuel cells be the future of sustainable energy? CHEMISTRY MOF-Based Materials for Next Generation Energy Applications BIOLOGY Mycelia: a promising lead to the ecological revolution 01 0 1 05 05 09 15 1 5 17 17 21 2 1 23 23 27 27 31 31
Is
What
The

IS YOUR HEART GIVING IS YOUR HEART GIVING YOU MIGRAINES?

YOU

MIGRAINES?

Migraines are a neurovascular disorder characterised by recurrent headachesassociatedwithautonomicsymptoms,withestimatesplacing migrainesasthe sixthhighest causeofyearsoflifelostduetodisability. Approximately 12% of the population of the western hemisphere suffer from migraines,and,althoughtheaetiology(thecause)canvary,arecentlinkhasbeen established between migraines, and a condition called the patent foramen ovale (PFO).

| 01 SCIENCEMIND WINTER 2023 TREADING WATER
Cardiology
Figure 1: Patent Foramen ovale (right) is when the hole between the right and the left atrium remains open in a child after birth. Thisholecanremainopenandrelativelysymptomlessalltheway into adulthood, but may predispose, to certain conditions, including migraines

A 2008 meta-analysis conducted by Schwedt et al. confirmed that the incidence of PFO in patients suffering from migraines was 39.872%, and that, similarly, the prevalenceofmigrainesinpatients withPFOwas 22.3-64.3%.

About 20-25% of the adult population has PFO but the incidence of PFO increases to 3050% amongstpeoplesufferingfrom migraine with aura (a classic migraine).

There are multiple proposed mechanisms by which PFO causes migraines,whichmayactinparallel. Thefirstis the theory of abnormal thromboembolism, proposing that tiny venous clots and platelet aggregates, which are normally filtered in the lungs, bypass the pulmonary circulation via the PFO, allowingthemtodirectlyenterthe arteries. This causes occlusion of these vessels, leading to hypoperfusion and thus symptoms of migraine, including the characteristic unilateral throbbing painandextremesensitivitytolight andsound.Thesuccessfultreatment ofsomemigraineswithantiplatelet therapy, such as aspirin or clopidogrelsupportthishypothesis. However, many migraines are resistant to this line of therapy, suggestingthatotherpathwaysmay alsobeatplay.

The second hypothesis involves vasoactive substances, including serotonin and calcitonin-derived gene-related peptide. These can transmit pain signals and may therebybeimplicatedinsymptoms ofmigraines.

Normally, these substances are broken down by monoamine oxidasesinpulmonarycapillaries.In patients with PFO, they can bypass thelungs,andarenolongerbroken down.Theysubsequentlymigrateto arterial vessels entering the brain where they can effectuate their pain-mediatingactionsbyactingon trigeminal ganglion cells that are involved in the dural neurogenic inflammatoryresponse.

Other studies have proposed a geneticlinkbetweenmigrainesand PFO,showingthatatrialshuntscan be inherited in an autosomal dominantfashion,andthatmigraine withaurawasinheritedinasimilar wayinsomefamilies.

Despite the pathogenesis being uncertain, Elbadawi et al. showed an improvement in migraine symptoms after transcatheter PFO closure.Thisisasurgicalprocedure in which a thin tube (catheter) is inserted into a blood vessel in the groin and guided to heart via this vessel.There,itfixesthehole,before removing the catheter. Although a promisingdiscovery,itisimportant to consider that only single-centre observations have shown a beneficial role of PFO closure on migraineprevention,whereaslarge, randomised control trials (MIST, PRIMA, and PREMIUM) reported negative results. Nevertheless, a 2021 meta-analysis by concluded that PFO closure was a safe procedure and could significantly reduce the mean number of migraine days and attacks, with numerous patients experiencing completemigrainecessation.

WINTER 2023

Cardiology 02 | SCIENCEMIND

To consolidate the differential findings of previous studies, Zhang etal.carriedoutameta-analysis in February 2022 looking at 3 randomised controlled trials (RCTs) and 8 retrospective case series (RCSs) with 1165 subjects. The results of this meta-analysis demonstrated a 50% reduction in monthly migraine attacks and migraine days after PFO closure (p=0.0295).Completeresolutiondid not reach statistical significance, likely due to insufficient studies includedintheanalysis.

Nevertheless, the higher the incidenceofaurainthesepatients, the greater the reduction in migraineattacksanddays,andthe higher the incidence of complete cessation of headaches after PFO closure. This suggests a promising new therapeutic approach to treatingseveremigraineswithaura.

Inpatients withoutaura, somedid have statistically significant reductions in migraine attack. Nevertheless,incidenceofmigraine days and headache reduction in these patients was not statistically significant, questioning the therapeutic potential of this intervention. Moreover, some patientsexperiencedmorefrequent migraineattackswithinthe4-week period after PFO closure, with symptoms persisting for several weeks. This may be due to the activationofendothelialcellsinthe left heart after PFO closure, which activates platelets. Platelet activation triggers their release of serotonin which may thus perpetuatemigraines.

Ifserotoninisindeedthecausefor these patient’s headaches, then antiplatelettherapysuchasaspirin orclopidogrelmayhelpresolvetheir symptoms.

Overall, this meta-analysis substantiated findings of previous studies implicating PFO in susceptibilitytomigraines.Although yielding controversial results for migraines alone, it certainly warrants re-evaluation of PFO closure as a therapeutic means for treating episodic migraines, especiallymigraineswithaura.

References

| 03 SCIENCEMIND WINTER 2023 Cardiology

Whether

04 | SCIENCEMIND WINTER 2023
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Can the growth and demise of rats predict human nature?

A mouse utopia was built by John B. Calhoun, where the animals were provided unlimited food and water, and full protection from predators and disease.Inthisutopia,theonlylimitingresourcewasphysicalspace.Calhoun, the American ethologist and behavioural researcher rose to fame through this gripping project - ‘Universe 25’. Theoretically, every whim of the mice was meant to be satisfied but how did it deteriorate into hell? And what does it meanforhumans?

In 1970, Calhoun attempted to conduct abehaviouralstudyof captivemicetoexplainhuman

society in an “ideal world” He namedhisproject‘Universe25’.The mice were provided a 9-square-foot enclosure which had numerous compartments for the mice to nest and explore. For the first 104 days, Calhounallowedfourbreedingpairs ofhealthymicetotheirnew,utopian environment. During this time, they marked their territories and birthed pups. Over the 104 days, the population of mice approximately quadrupled! What was interesting was that the mice would huddle togetherduringfeedtimeandcrowd incertainareasdespitethevastness

in space available. It seemed as thoughtheywerelivinginparadise.

The project took an abrupt turn nearlyayearinwhenthe population density began to peak. The population growth greatly slowed due to crowding behaviour, now doublingevery145daysinsteadof55 days. When the number of rodents reached620,micebegantonaturally form groupings.Micethatdidnotfit into any of the groups became severely socially isolated. Mice who are unwelcomed in the population face extreme vulnerability, both for their mental and physical health. In normalcircumstances,isolatedmice wouldhaveimmigratedtofind

| 05 SCIENCEMIND WINTER 2023 Neuroscience
UNIVERSE
25:
TREADING WATER

another group, however, within Universe25,theywerestarvedofthis option.Therewasalsoaformationof a hierarchy between them, and the mostdominantmicewereextremely aggressiveandlarge,thuscalledthe “alpha mice”. These mice began to attack the group, rape, and even practicecannibalismattheexpense oftheirpeers.

As a result, many males began to become negatively impacted psychologically. They excluded themselves and as a consequence, sleptandatebythemselves. Female mice even began to attack their own pups as taking care of their nestsinthemiddleofsuchaviolent and chaotic environment was exhausting. Some would completely withdraw themselves from their motherly duties, ignore their pups andquitmatingentirely. Theutopia became hellish and showed a breakdown of social order named the“behaviouralsink”.

As a result, a low birth rate was observedandanincreaseinmortality

in younger rodents. A new class of male rodents appeared which were namedthe“beautifulones”whohad no perception of the “normal” lives thatmiceledbeyondtheenclosure. These mice refused to mate with femalesorto“fight”fortheirspace.

They were only concerned with food, sleep and grooming, appearing in perfect health and unruffled. Eventually, most of the population consisted of “beautiful ones” and “isolated females”. During this stage homosexuality was also observed which led to a greater decreaseinbirthrate.Eventually, the beautiful ones outnumbered the alphamales,buttheycontinuedto exist solely instead of mating or creatingnewroles. Thisparadoxof thebeautifulonesrevealedthatselfdestructive patterns emerge when livingalifewithoutpurpose.

Calhounexplainedthatheobserved two stages of the death phase: the “first death” and “second death”. The first death stage was characterised by rodents being emptyofdesiretomate,raiseyoung

orestablishtheirrolein society.Thelatterstage was from juvenile mortality reaching 100%andreproduction being0%.

Takenfrom:

https://www.sciencehistory.org/ distillations/mouse-heaven-ormouse-hell

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Neuroscience
Figure 1: An image picturing a rathabitatfromCalhoun's1962 article.

Over the course of the 25 repeated experiments, the same sequence of eventswouldoccur:

The mice would meet, mate and breedinlargequantities.

The number of mice began to plateau,ratherthanincrease. Increasing pressure caused by reduced space led to rodents developing hostile and/or antisocialbehaviour.

The populations would permanently diminish with no recovery,

WhatifUniverse25wasappliedto humanity?Wouldhumanitysuffer the same fate? This project was wildlycontroversialwhenfirstmade public as Calhoun’s theory raised concernsthatsocialbreakdownseen inUniverse25couldbeametaphor for the fate of humanity. Thus, Universe 25 has been an interest of city planning councils, architects, andgovernmentagenciesaroundthe world.

However, Calhoun did not believe thathumanitywasdoomed.Insome of his experiments, rodents developed innovative tunnelling behavioursoraddingmorerooms allowed animals to live in highdensity environments without being forced into unwanted contact with others. Writing in a report summary in 1979, Calhoun noted that “no single area of intellectual effort can exert a greater influence on human welfare than that contributing to better design of thebuiltenvironment.”

Universe 25 offers an important insight into how humankind could demise. The “beautiful mice” particularly show that if individuals donotobtainaproductiverolein

society, and if they do not have established relationships and role modelsintheirenvironment, people couldlosetheirpurposeinlife

Mostimportantly,Universe25wasa utopian environment made to test thepotentialproblemsofcrowding, somethingthatthemodernworldis rapidly reaching. However, this meansthattoreplicateitinhumans, wewouldhavetoensuretheendof disease, hunger, and natural disasters. Thus, it is not currently a perfect parallel to humanity. Furthermore,criticshavealsoargued that the end of the mouse utopia may not have created an overpopulation problem but an environment where more aggressive mice were able to control the territoryanddominateotherrodents. Thus,theissuewasmoresowithhow the area was controlled rather than lackofareafortherats.

References

Neuroscience
| 07 SCIENCEMIND WINTER 2023
With modern century ideals, do you think Calhoun’s experiment could apply to humans?
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WHAT IS IT LIKE TO BE AN INSECT?

Foralongtime,insectswerethoughttobemechanicalmachines.Beingsthat actbasedoncoldinstinctandwithlittletonosubjectiveexperience.Wenow know that this is simply not true. Social insects in particular such as ants or bees seem to be almost magical in their ability to do extraordinary tasks with brains the size of a pinhead or less. To understand how scientists are peering into the minds of insects, I interviewed two leaders in the field: Professor Martin Giurfa from the University of Toulouse and Professor Albert Cardona workingatthelaboratoryofmolecularbiology(LMB)inCambridge.Thisarticle willfocusprimarilyonmembersoftheHymenopteraorder,thelargestorderin theinsectclass.

MARTINGIURFA

Martin Giurfa is a scientist withanextraordinarystory. BorninArgentinain1962,

he studied biology at the University of Buenos Aires during the reign of theNationalReorganisationProcess, a brutal military dictatorship which persecuted left-wing political opponents. In protest, Giurfa chose to join the left-wing party ‘Partido Intransigente’,wherehehadquitean influentialrole.Thiswouldeventually allow him to meet Prof. Josué Núñez, a founder of the field of behavioural physiology in Argentina.Giurfahasspentmuchof hiscareerstudyingbees,inparticular honeybees (Apis Mellifera). An importantcontribution

hemadetothefieldofinsectwashis discovery that honeybees mark flowers they have already visited withaspecificpheromonesoasto not visit the same flower twice GiurfaiscurrentlyaProfessoratthe UniversityofToulouse.

ProfessorNúñezwouldprovetobea very useful connection for Giurfa since he knew Professor Randolf Menzelwell.Menzelwasastudentof Martin Lindauer, a pioneer of the ethology field who specialised in learning and memory. Lindauer was one of the students of Karl von Frisch, one of the first scientists whoseworkonbeeswasseenasso important that it was awarded the NobelPrizeinPhysiology

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Neuroscience
DEEP DIVE

orMedicinein1973.Weshall explore Martin Giurfa’s career and contributions to thefieldofinsectcognition abitlaterinthearticle.

Bees are members of the Hymenopteraorderwhichis itself composed of bees, wasps and even ants (see figure 1). However, in many ways, bees are the insects capable of the most complex of behaviours and thus if one could understand how bees perceive the world, that would go a long way towardshelpingusseehow

all Hymenoptera members might think. Let us first delve into the evidencethatprovesthathoneybees have an intricate, subjective experience of the world around them.

One of the most fascinating behaviours honeybees can carry out is the construction of intricate combs both to store food and to houselarvae.Infact,CharlesDarwin called the ability of bees to make combsas“themostwonderfulofall known instincts”. These combs are very mathematically peculiar since the hexagonal hive construction is the architecture which allows space to be divided into the largest area with the smallest perimeter. The proofofthistookalmost2000years to be determined but was finally accomplished in 2001 by the mathematician Thomas C. Hales. Regardless of the mathematical elegance of the comb, the behaviouralinsightthatgoesbehind it is also fascinating and could be arguedtogofarbeyondjustinstinct.

details related to honeycomb construction. Even just by observing honeybeesastheywereconstructing their combs, fascinating behaviours could be observed. One such behaviour was that bees had great flexibilityduringhiveconstruction, withtheabilitytochangeacomb’s dimensions depending on whether itwastobeusedbyadroneorthe differently shaped compartment used to host a queen.Moreover,as can be shown in figure 2, bees are abletoadapttheconstructionofthe hive depending on the surface they encounter. This is just one small example of the amazing complexity of honeybee behaviour and if a readerisinterestedtofindoutmore, I would strongly recommend Professor Lars Chittka’s book ‘The MindofaBee’.

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Moreover,afascinatingbehaviourthat onlyhoneybeesarecapableofdoing whichisclosertowhatMartinGiurfa worksonisthebeedancealsoknown as the waggle dance. First, the performing bee will run a certain distance vertically along the hive. Then she will run in a semicircle to theleftandtotheright.Aristotlewas the first to hypothesise that bees could communicate the location anddistance whereotherbeescould find flowers using repetitive, choreographed motor movements. Thisfindingwas rediscoveredin1788 by Ernst Spitzner who interpreted the dance somewhat correctly since he implied that bees used it to communicatethelocationofagood supply of nectar. However, Spitzner’s findingswereforgotten. Thescientist who would finally decipher both the function of the waggle dance andthewayitencodesinformation wasKarlvonFrisch.

Von Frisch had, since the 1920s, hypothesised that bees could use their‘dance’tocommunicateto

other bees the location of valuable sourcesofnectarbuthewasnotsure how this might work. When Von Frischsawthis,hehadnoideahow this dance might encode information.However,in1945,hehad several breakthroughs. He started changing the distance at which a foodsourcewasprovidedtothehive andobservedtheresponsethebees had. He saw that the bees very quickly learnt to look at the new location. Von Frisch therefore wonderedwhetherthewaggledance mightbeabletoencodefordistance.

He found that indeed, bees that were exposed to food sources far away had a different looking waggle dance than those exposed to food close. The distance is encodedbythelengthofthestraight line bees run. Von Frisch also discoveredthattheorientationofthe dance does not stay constant. It follows the direction of the sun, which allows bees to also know whichdirectiontogointofindthe food source. This is particularly useful since bees can detect polarisedordirectionallightandthe pattern of polarisation is different dependingonwhereonelooksinthe sky, allowing bees to orient themselves very rapidly. What is really amazing is that honeybees can adapt the bee dance to different contexts and situations, such as finding a new place to build a hive. This capacity for abstractness is a major reason for why many people consider the bee dance as a language - one of the mostintricateknowntoMan.

Let’s now get back to Martin Giurfa andhiscontributionstothefieldof insectneuroethology.Giurfamadea

Neuroscience
| 11 SCIENCEMIND WINTER 2023
Figure 2: Honeycomb construction on differentmaterialsfollowingworkbyFrancois Huber.

landmark discovery that bees can understand several key concepts such as the concept of ‘sameness anddifference’butalsoof‘up’and ‘down’. This paper was really groundbreaking and showed the extenttowhichbeesarecapableof conceptual learning, the ability to categorise objects. In fact, when I askedGiurfawhathismostsurprising discoverywas,hementionedthisone (althoughhisfirstanswerwastosay, ‘everything’).However,Giurfadidnot stop there. He also made seminal contributions to our understanding oftheimportanceofpheromonesin guidingbeebehaviourandhasdone extensive work on olfaction in honeybees.

Martin Giurfa’s interest in the molecular mechanisms of insect behaviourhasledhimtoexplorethe mushroombodiesandwespentalong time discussing their extraordinary structure. The mushroom body is found in all insect brains and is in many ways homologous to our hippocampusandassociationareas. The mushroom bodies of honeybees areparticularlyinterestingsincethey respond to different sensory information or modalities such as taste,smellandvision.Inotherwords,

bthey are multimodal whereas the mushroom bodies of fruit flies (Drosophila melanogaster) are unimodal (only respond to olfactory stimuli). The mushroom body is what allows honeybees to perform conceptuallearning.

However,animportantquestionstill remains. Why are the honeybee mushroom bodies so much more developed and complex than that of other insects? Andwhyisitthat honeybees and bumblebees are capableofsuchcomplexbehaviours. Acentralhypothesismightbethat it is due to the social nature of theseinsects. However,solitarybees also require large behavioural capacities, in particular when it comes to navigation since if a honeybee colony loses one individual,thatisnotveryimportant butifasolitarybeecannotreturnto herhive,thatbee’sprogenywillnot survive either. In fact, even the microscopic bee Nomioides minussimus possesses a complex homing behaviour. In order to show thatthesocialnatureofinsectsisa keyindicatorastohowcomplexthat insect’s behaviours can be, more behavioural research needs to be doneonotherHymenoptera,suchas otherbee,waspandantspecies.

A useful way of achieving this might be through the use of new electrophysiologyprotocols enabling us to very rapidly assess whether different insects possess different neuronal pathways. Martin Giurfa has very much pioneered this idea to understand complex behaviour by usingavirtualrealityprotocoltoallow bees to remain still whilst they perform complex tasks. Doing this allowsGiurfatokeepabee’sheadstill, thus allowing electrodes to be implantedintothebee’sbrain.

12 | SCIENCEMIND
Neuroscience
Figure 3: Computerised model of a honeybee brain.

It’spredictedthatthiswillallowusto haveamorecomparativeapproachto studyinginsectbehaviour.Another methodthatcouldallowustobetter understand insect brains are connectomicmethods.Thismethod involvesimagingsynapticconnections betweenneuronsandusingthemto createacomputerisedmapthatcan beusedtounderstandthedifferent neuronalcircuitsfoundinthebrain.

ALBERTCARDONA

CardonadidhisPhDattheUniversity of Barcelona looking at the developmentofplanarians.Forthis work,Cardonahadtomakeextensive useoftheelectronmicroscope.This microscopeworksinasimilarwayto aclassiclightmicroscopeexceptthat itusesabeamofelectronsinsteadof photons.Thismethodpermitsfor bothahighermagnificationand resolution.Infact,samplescanbe magnifiedbyupto2milliontimes.

Thereareseveraldifferenttypesof electronmicroscopy.Theonemost commonlyusedforconnectomics researchisthetransmissionelectron microscopeorTEM.ThisEMmethod isverypowerfulsinceitallowsfor parallelimageacquisitionandthus speedsupimagingtime.Therate limitingstepwiththistypeofimaging isthatextremelyfineslidesare neededandhandlingoftheseslides needstobeextremelygentle.TEMhas beenusedsincethestartofthe connectomicsfieldsincethefirst organismtohaveitsnervoussystem mappedwasC.elegansin1986which wasdoneusingTEM.TEMimagingcan nowbedoneveryrapidlyusing GridTape,forinstance,asamethodto automateimaging.

Interestingly,theterm‘connectomics’ was only coined in 2006 by Olaf Spornsinthecontextofmappingall theneuronsinthehumanbrainusing methods such as Diffusion Tensor Imagingorviraltracing.However,the resolution provided by DTI is far smaller than that provided by TEM and this means that DTI can only reallybeusedtotracelargeneuronal tracts. Viral tracing also takes longer than using EM and is less precise. Another method currently used for connectomicsis brainbow

AlbertCardona,firstatJaneliafarmin the US and now at the LMB in Cambridge, has been central in mapping a large amount of Drosophila Melanogaster larvae’s 9000neurons.However,hedidnotdo this alone. Dozens of labs around contributed too, using the computer program CATMAID (collaborative annotationtoolkitformassiveamounts ofimagedata)tosiftthroughallthe dataandarrangeitinacoherentway. ThereasonwhyAlbertchosetowork on Drosophila is that a vast array of molecular tools are available to scientists to label and manipulate individual neurons but also because almost all the different neuronal cell typeshavebeencategorised.

Albert’s lab, working with collaboratorsfromaroundtheworld, startedpublishingthereconstructed nervous system data from 2016 onwardsandmadeamassiveimpact when it occurred. It was clear to manyneuroscientistsatconferences where Albert spoke that the way neuroscience would be done had changed forever. The sheer amount of data is enormous. Just for a microscopicDrosophilaflylarvae,the imaging data alone takes about 8 terabytesofstoragespace.

Neuroscience | 13 SCIENCEMIND WINTER 2023

Thekindofresolutiononecangetby using the EM approaches for neuronaltracingisquiteastounding, asshowninfigure4.Thisneuronis called a kenyon cell and is the output neuron of the mushroom body. In order to find such kenyon cells,anotherresearcherattheLMB, Gregory Jefferis, developed a set of tools and placed them in an R package called NBLAST. Using NBLAST, connectomic data can be used to identify specific neurons, lookattheirpre-andpost-synaptic connections and observe where neuronsarefoundrelativetotherest oftheDrosophilaCNS.

responsibleforactionselectionwork, for instance, if the connectome shows two connections to be inhibitory, one might suggest a modelwheredisinhibitionoccursso that an action is selected. This therefore can lead to a testable hypothesisandcanhelptodecipher how a specific part of the nervous systemworks.

Connectomic data needs to be placed in a functional context, however,sothatonecanunderstand which neural circuits might be involvedinwhichbehaviours.Oneof Albert’scollaborators,ProfessorMarta Zlaticistryingtodoexactlythis.She usesCalciumimagingorGCaMPto visualiseneuronalactivityandthus determine which neurons are active during what behaviours

Connectome data allows her to predicthowtheneuronalcircuits

WhenIaskedAlbertwhathethought it was like to be an insect, he said that first one would either be a parasitic wasp (since most insect speciesareatypeofwasp)ortobe anant(sinceantshavethegreatest biomass of any insect). However, in termsofexperience,antsandwasps are very different. Most wasps are solitary whereas ants are found in largecolonies.Moreover,bothwasps and ants are found in almost every continent in the world and inhabit vastlydifferentclimatesandhabitats. These major differences mean that we are still very far from understandingthesubtledifferences found between different insect brains. There is one major common point,however,betweenwhatMartin and Albert have said: insects have farrichersensoryexperiencesthan we do and we still have very little ideahowthismighttranslateinthe insect mind. Connectomics work in other insect species might give us some insights into the kind of behaviours that specific species can orcannotperform.

References

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Neuroscience
Figure 4: A kenyon cell reconstructed using NBLAST.

The blood test that can help diagnose Alzheimer's

Alzheimer's disease is a chronicneurodegenerative disease whichcausesprogressivememoryloss. The four main characteristics of the condition are neurofibrillary tangles, neuritic plaques, the buildup of amyloid beta peptide, and the hyperphosphorylation of the Tau protein in neurons. (De-Paula et al., 2012)

EventhoughAlzheimer'sdiseaseisthe most common form of dementia, it takes, on average, over four months from onset of symptoms to diagnosis, withsomewaitinguptotwoyears.This delay in diagnosis leads to people missingoutonsupportandtreatment that could improve symptoms. (Alzheimer's Society, 2022) Before the early2000s,Alzheimer'sdiagnosiswas post-mortem, so although the diagnosis procedure has come a long way,thereisstillawaytogo.

Currently, the process of diagnosing Alzheimer's is extensive. After presenting to the GP, the patient will have tests for memory and problemsolving,andaneurologicalexam.

This will often be followed by excluding other conditions that can leadtodementia-likesymptoms,such as delirium, depression, thyroid problems, or excessive alcohol consumption. The patient may then have a lumbar puncture to measure the level of change in tau and betaamyloidintheCSF.Brainscanssuchas CT,MRI,orPETscanscansupportthe diagnosis or help to rule out other causesforsymptoms.

The journal article titled “Brainderived tau: a novel blood-based biomarker for Alzheimer’s diseasetype neurodegeneration” forms the basis of this article. In their paper, they explained how previous use of blood-based or plasma-based biomarkers for amyloid beta and phosphorylated tau can be useful in looking for Alzheimer's but are not specifictoAlzheimer'sdisease.

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SHALLOW DIVE Medicine
Fig1.MRIscanshowing neurodegenerationina normalbrainversusabrain withAlzheimer’s(Butch,2017)

This means they can not be used as diagnostictools.Theirresearchproject aimed to create an anti-tau antibody thatonlybindstobrain-derivedtau,in the hopes that this would be more specific to Alzheimer's. If the biomarker is specific to Alzheimer’s, this means that it can be used as partofascreeningtool.

They found that the brain-derived tau was significantly correlated to the presence of Alzheimer’s, whilst the previously used blood-based tau was not. This means that the blood-based tau, whilst useful, has a large overlap withotherdiagnosticgroups,meaning it is difficult to confirm a single condition-leadingtopoordiagnostic utility. The brain-derived tau was also able to identify Alzheimer’s disease in an autopsy, even in comparison to other neurodegenerative conditions. It was found to correlate to global neuritic plaque counts found in patientswithAlzheimer’spost-mortem. Examples of the neurodegenerative conditions that the brain-derived tau could distinguish between were brain degeneration, parkinsonian disorders, andhealthycontrols. This means that different results in levels of brainderived tau were present in each of these groups, leading to an easier path to diagnosis. The brain-derived tauwasalsofoundtohaveaninverse relationship to the progression of cognitiveperformance.

The conclusion from their project was thattheblood-derivedtauisatoolthat shows specificity to Alzheimer's disease, and therefore has the potential in the future to be used as a diagnostic tool in the future. A reason that the brain-derived tau was able to be more specific than the blood-based tau was due to the suggestionoflackofinterferencefrom peripheral tau. (Gonzalez-Ortiz et al., 2022)

At the end of the day, there is an urgent need for a simple diagnostic toolforthediagnosisofAlzheimer’s A blood test would allow for earlier detectionanddiagnosis,meaningthat treatment can be started quicker for patients. The time between the onset ofsymptomsanddiagnosisisacritical period. Most of the treatments available for Alzheimer’s have a significantly better outcome when started earlier, and may stabilise the patientsforlonger,leadingtoabetter qualityoflifeforanextendedtime.A blood test also makes diagnosis more accessible, both economically and in morediversepopulations.Especiallyin countries with private healthcare services, where many people do not havehealthinsurance,adiagnosiscan be incredibly costly, with several procedures and scans to come to a conclusion. By providing a simpler diagnostic tool, a significantly large number of people would have access toadiagnosis.(Alzheimer'sAssociation, 2023)

Atthemoment,noavailablesingletest can diagnose Alzheimer’s, despite several click-bait type articles being put on the internet, and several selfdiagnosistestsmarketedtoconsumers. Diagnosisofthediseaseshouldonlybe carried out by the set procedures carried out by doctors. However, the future of diagnosis is through developments such as brain-derived . The next steps for the biomarker willmostlikelybevalidationthrougha broaderrangeofpatients,beforebeing used in conjunction with current procedures.

References

16 | SCIENCEMIND WINTER 2023 Medicine

Poppies to Pills

THE DEVELOPMENT OF SYNTHETIC OPIOIDS

Opiumderivativeshave an illustrioushistoryinpharmacologyand havebeenused in medicaltreatments since their legalisationin1775.Despitetheireffectiveness atreducing pain signals,therehavealwaysbeentwosidesto the use of opioidmedications.In the operatingtheatre,early opioidswere used tomanageacute pain. Onthe otherhand, opiumhas been recreationallyusedsince3400BC.Interestingly,peoplebelieved that painwas deeply linkedto our spiritualityanddruguse eliciteda ‘supernatural’ experience

The first actual developments in opioid synthesis aimed to produce sedation with intense analgesia. Drugs at the time only caused partialanalgesiaandhadmanyside effects, most notably intense respiratory and cardiac depression which increased the number of complications in post-operative recovery. In 1953, Paul Janssen, a Belgian chemist, was working on new painkillers to find more moleculeswithhigherpotencyand specificitythantheonesbefore.He speculated that with increased potency and increased specificity would come increased safety. In addition, he hoped to reduce the harmful side effects as well as the addiction that often came as a dependencyonthedrugforms.

The side effects and potency go hand in hand with the stereoisomeric structure of the compound.Theanalgesicnatureof thedrugisintimatelyrelatedtoits 3Dshape,therefore,minorchanges in the conformation of a narcotic moleculemaysignificantlyalterthe pharmacologicactivity.Atthetime, themainopioidsavailable,

morphineand meperidine,were lessoptimalatcrossing theblood-brainbarrier andstimulatingopioid Qreceptors. Furthermore, meperidineisan addictivesubstance Thisisbecausethesame decreaseindopamine andnoradrenalinethat helpswithpainreliefis associatedwithfeelings ofnumbnessandrelaxation. Aftertakingmeperidineand otheropioids,jitteriness and anxiety are common due to the body compensating by raising noradrenalinelevels.

Chemists began experimenting with different arrangements of meperidine by adding benzene rings to increase lipid solubility due to their non-polar characteristics,whichincreasesthe analgesic activity. This property is known as lipophilicity and is particularly relevant to opioids as theyhavetocrosstheblood-brain

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Pharmacology
Meperidine

barrier. However, the change in 3D shape due to the phenyl groups made the interactionwithreceptorslessoptimal.

Itwasfoundthatbyseparatingthephenyl group bonded to a carbon on Nmethylpiperidine by three carbons and adding a hydroxyl group to the third carbon a new compound could be producedcalled phenoperidine.This compoundwas20timesstrongerthan morphine.Continuing attempts eventuallyresultedin the arrival of fentanyl,the strongest synthetic opioid, witha 100-300 times greater potency thanmorphine

Itbindsmu-opioid G-protein-coupled receptors, which inhibit neurotransmitter release, decreasing calciumion concentration.The bindingeffectively blocks nociceptive afferentnerves, reducing sensations ofpain.

Postsynaptically,potassium channels areopened,which hyperpolarize the membrane, resulting in a greater threshold foranaction potential to form. Various Opioid agents, of which fentanyl is the most prominent, can decrease serotonin reuptake and increase thereleaseofintrasynapticserotonin.

exposure is less likely to cause addiction. However, these same fleeting effects lead to an increased number of overdoses. The highly publicised death of the artist Prince duetoanaccidentaloverdosebrought the topic under the spotlight. Ever since,thenumberof overdosedeaths hasbeenincreasing asfentanyliscut into other opioids on the street, such asmorphineandheroin.Itischeapto synthesise and as a result, is readily accessibleandwell-stocked.

Opioid-induced hyperalgesia is a phenomenon notentirelyunderstood by academia. Treating pain with opioids can result in increased sensitivity to nociception. When patients receive opioids under anaesthesia, several studies have demonstrated increased opioid requirements after surgery and worse pain scores. Short-acting opioids such as fentanyl may provoke OIH more than longer-acting ones, as OIH increases when pain relief wears off andopioiddosesmustberepeated.

Duetoitspotency andspeed,itisoften used in combination with other anaesthetic drugs, such as propofol, to reduce the intense stimulus of surgical pain. Fentanyl has quickly become the industry standard, but is this the best decision to make? The analgesic and euphoriceffectsareshort-lived,shortterm

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Pharmacology
Fentanyl Phenoperidine

Since the introduction of synthetic opioidsintothemarketplace,American overdose deaths have almost tripled. This is largely due to the overprescription of opioids by American doctors and incentivisation by insurance companies to make expensive pain medication more common. Some anaesthetists are opting to remove fentanyl from their operating theatres completely, choosinginsteadtouseregionalnerve blocks such as lidocaine and epidurals. It is apparent that the dangertosocietythatsyntheticopioids pose is vastly underappreciated. Althoughtheliteratureisunitedonthe safe doses and administration of fentanyl, there is still more to be uncoveredaboutthelong-termmedical and social impact of such a powerful drug.

References

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Pharmacology
Figure1:Threewavesofopioidoverdosedeaths: Thisgraphshowsthe drasticincreaseinopioidrelateddeaths,specificallyduetosynthetic opioids
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THE GREAT UNEQUALISER:

How COVID-19 Made Health Disparities Worse in the UK

"It’s the great equaliser,” proclaimed Madonna in a videopostedtoInstagramin 2020. Sitting in a rose petal-filled bathtub, the American singersongwriter delivered a bizarre sermon to her millions of followers about how the novel coronavirus “madeusallequalinmanyways”.

Perhapsintheory,apandemiccould have been just the thing to unite populations and cross societal divides.Insomerespects,itdid.The globalresearchefforttounravelthe mysteryofthisunknownvirusledto the developmentofvaccinesinless than a year; a process which could previouslytakeadecade.

Butyoudon’thavetolooktooclosely to find that the effects of COVID-19 were far from “equalising” (and Madonna’s followers were quick to criticise the tone-deaf video, which was subsequently deleted). If anything, the pandemic shone a light on and exacerbated the existinggapspermeatingsociety

In the UK, it was suspected early in the pandemic that ethnic minority communitiesweredisproportionately affected by COVID-19. Researchers from LSE published a study in May 2020 that found COVID-19-related hospitaldeathsintheUKwere

twiceashigh inthe Bangladeshi population, almost threetimesashigh in the Pakistani populationand almost fourtimesashigh in the BlackAfrican population comparedtothewhiteBritish population.

Asthevirusevolvedand infectedmillionsacross thecountry,the higher mortalityratespersisted inethnicminority communities.Inthe second wave duringthewinterof 2020/21,mortalityriskwas highest amongpeoplein the Bangladeshiand Pakistani groups.The risk remainedhigh amongpeople inthe Black Caribbean andBlack African groups butwaslowercomparedtothe firstwave.Inthefollowing winter’s Omicronwave, BangladeshiandPakistani mortalityrateswere twoto threetimeshigher thaninthe whiteBritishgroup,while peopleinthe BlackCaribbean andmixedethnicitygroups also showed highermortalityrates

SHALLOW DIVE Business/Law | 21 SCIENCEMIND WINTER 2023

Thesestatisticscouldbedueto severalfactors.Firstly,peoplefrom minorityethniccommunities (particularlythosefromBlack Africanbackgrounds)were more likelytobeemployedaskey workersinthehealthandsocial caresectors leadingtoagreater riskofexposure. Underlyinghealth conditionswerealsomore prevalent amongolderpeoplein thesecommunitieswhichmade themmorevulnerableto infection;thiswasespecially thecasefortheBangladeshi population.Ethnicminority communitieswerealso morelikelytolivein denselypopulatedareas comparedtothewhite Britishgroup,acondition whichwouldhaveexpedited thespreadofthevirus. Regardlessofthecauses, thisdisparitymadeitclear that keysocietal inequalitieswerebeing overlooked by policymakersinaddressing thepublichealthemergency.

The introductionofvaccines didhelptoreduce mortalityrates tosomedegree:it wasestimatedtohaveprevented over150,000hospitaladmissionsin EnglandinMarch2022.However, vaccinationratesinpeoplefrom minorityethnicbackgroundswere noticeablylower thanratesinthe whiteBritishgroup.Inthesameyear, theHealthFoundationreportedthat thosewhosemainlanguagewas notEnglishwerelesslikelytohave beenvaccinatedorreceiveda booster –only 53.9%hadreceived threejabs comparedto74.4%of peoplewhoprimarilyspokeEnglish.

Theyalsofoundthat people across most ethnic minority groups were less likely to have received three doses comparedtothewhiteBritish group. In London, people from the Black Caribbean community made up the highest proportion of unvaccinated adults (43.5%), followed by those in the Black African group (32%) and those of mixedethnicity(31.8%).

The prevalence of vaccine hesitancy among ethnic minorities could be attributed to factors such as mistrust of information regarding the vaccine’s efficacy and the systems delivering it; inability to access healthcare services; and a lack of cultural competency inthe services and information provided. These elements need to be considered in the rollout of the vaccination programme to encourage its uptake across all communities

COVID-19 has spotlighted existing societal inequalities that can no longer be ignored. Ethnicity is only one aspect of the healthcare disparitiesprevalentintheUKwhich need to be addressed. We cannot trulydeclarethatweareina“postpandemicworld”iftheissueswhich made the pandemic so devastating in the first place are allowed to continue. A longer-term public health strategy that actively considers the diversity of the UK’s population must be made to prevent a disaster of this scale fromhappeningagain.

REFERENCES

22 | SCIENCEMIND WINTER 2023 Business/Law

Pee Power: could urea fuel cells be the future of sustainable energy?

idyouknowthattheaverageadult producesapproximately 11kgof urea each year? Until the 20th century, this was considered waste. However,overthepastseveraldecades, researchers have explored ways to turn what is believed to be a biological commodity into a next-generation sustainablesourceofelectricity

Theoriginsof‘liquidgold’

Urineinwastewaterwasfirstsuggested as a renewable energy source in the 1970's but has only gained significant development and critique in recent years. The key component of urine is urea,anorganiccompoundthatcanbe electrochemically oxidised to produce carbondioxide,nitrogengas,water,and electricity. With the world’s increasing population and energy dependence on fossilfuels,ureahasbeensuggestedto be a good energy alternative for both finite resources and other sustainable fuels.Forinstance,while hydrogen fuel cells are more environmentally friendly than coal and natural gas, they are expensive to manufacture and dangeroustotransport.

There are many examples of fuel cells being used to generate electricity today, such as direct methanol fuel cells and phosphoric acid fuel cells, butdirectureafuelcells(DUFCs)have shown incredible technological potential. Urea can serve as an excellent source of electricity and is described as a hydrogen-rich chemical fuel,witha 6.67%wt hydrogen.Luckily forus,itisinfinitelyavailable.Itcanbe oxidised in acidic, alkaline, or neutral conditions, allowing for different fuel celldesignstobepossible.Forexample, in a neutral-medium DUFC, a very simple electrolyte of sodium chloride (NaCl) is used. In essence, this means electricity can be generated from precisecombinationsofurineandtable salt! In this reaction, chloride ions are oxidised to form chlorine gas, which then undergoes disproportionation, meaning the chlorine gas is both oxidised to form hypochlorous acid (HOCl), and reduced to form chloride ions (Cl-). This reaction generates hydrogen ions, so an acid-resistant catalyst must be used, such as a titanium-coated metal. Interestingly, unlike other biocatalysts, DUFCs can work with natural organisms found in soil, compost, and urine to carry out nitrification and denitrification processestogenerateelectricity.

D | 23 SCIENCEMIND WINTER 2023 TREADING WATER
Technology
Figure1. Chemicalstructureofurea

How do direct fuel cells work?

Structurally, DUFCs are constructed from two electrodes, an anode (positively-charged electrode) and a cathode (negatively-charged electrode). The charges of these electrodes are vital for producing electricity, as they determine which species will be attracted to the electrodesinordertobeoxidisedor reduced by the loss or gain of electrons,respectively.

The generation of electricity using ureaworksonthissimplepremiseof reduction and oxidation, commonly referred to as redox. The most common type of urea fuel cell is alkaline, as it is less susceptible to corrosion than acidic ones. In alkalinefuelcells,ureaisoxidisedat theanodetoproduce N2, CO2 and H2O,and oxygen isreducedatthe cathode to form hydroxide (OH-) ions which travel through an anion exchange membrane. The transport of these OH- ions completes the electrical circuit, generating electricity.

Increasing efficiency: introduction of novel fuel cellcatalysts

While DUFCs display an exciting potential, there are various aspects of their design which need to be enhanced in order to make them viable for industrial use. A major example of this are the designs of theelectrochemicalcatalystsusedin the fuel cells. The catalysis utilises transition metal complexes which are highly porous to allow a large surfacearea fortheredoxreactions to take place. More precisely, transitionmetalsincreasetheredox reactions taking place in the fuel cells without being used up or damagingthemselves.

The most common catalyst in alkalinefuelcellsdesignsis nickel.It is an ideal catalytic candidate becauseitisreadilyoxidisedtoits+2 oxidation state in an alkaline mediumtoformNi(OH)2.Thisability to form multiple oxidation states quicklymeansnickelcomplexescan donateoracceptelectronsfromurea with ease, accelerating the rate of ureaoxidation.However,justaswith the developments in the fuel cell’s technological design, there have beensignificantbreakthroughswith the designs of novel catalysts. For example, in 2018, scientists developed a nickel molybdenum oxide catalyst witha much higher efficiency than traditional (and expensive) fuel cell catalysts, like platinum,whichwasabletooxidise ureaatmuchlowerenergycosts.

Figure 2. Chemical equations for the electrochemical oxidation of urea in alkaline conditions
WINTER 2023 24 | SCIENCEMIND Technology

Whilethecentralnickelatomisstillinthe +2 oxidation state, the design of this binary oxide catalyst generated higher yields and shorter reaction times. Since 2021, the concept of combining these binaryoxideswithnanoparticleshasbeen suggested- an even more promising development.

Where do we need to go from here?

Ultimately, DUFCs have displayed a significant biochemical potential to help combat the climate crisis by generating electricity from something ubiquitous to humanlife.Whileprogressonthedesign andapplicationsofthesefuelcellsisstill advancing, researchers must ask themselves some important questions to ensureDUFCsareimplementedinasafe and sustainable way. For instance, there are still concerns about certain byproducts, like nitrous oxides, being releasedaspollutants.Ontheotherhand, the cost of utilising DUFCs is currently veryhighwhichraisesthequestion, how can we turn our own waste into a new formofenergy?

References

| 25 SCIENCEMIND WINTER 2023
Technology
WINTER 2023 26 | SCIENCEMIND JOIN THE AWARD WINNING SCIENCE MAGAZINE AT KING'S COLLEGE LONDON LINKTR.EE/SCIENCEMIND Enhance your creativity by bringing the authors' and editors' words to life as part of the design team! No previous experience required! DESIGNERS JOIN US!

Metal Organic Framework Based Materials for NextGeneration Energy Applications

WhileLithium-sulphur batteriesseemtobea promisingcandidate,they provedtohaveasignificant challenge.Firstly,inert electrochemicalreactionsoccurdue totheinsulatingpropertiesof sulphurandinsolubleLi2S(2).

Increased global energy consumption drastically affectsenvironmental

changesandclimateissues,requiring extensive research to develop new, renewable, and efficient energy sources. As conventional lithium-ion batteries (LIBs) reach their energy density performance limit, developing new electrodes and storage materials remains one of the most significant difficulties in energy development. Various nextgeneration batteries, such as Lithium-sulphur batteries (LSBs), drewtheattentionofmanyscientists duetotheirhightheoreticalspecific energy (2,500 Wh kg-1) and specific capacity (1,675 mAh g-1) when compared to LIBs (270 Wh kg-1). Moreover, the low cost and high abundance of nontoxic sulphur increase the potential for LSBs production.

Secondly, anode corrosion, poor cycling stability, and high selfdischarge rates are some of the “shuttle effect” results. Upon dissolution of polysulfides, the physical state of sulphur in the discharging/charging process will undergo a solid-liquid-solid transition. When sulphur in a solid state is discharged to higher order polysulfide, low-order polysulfides willbeproducedduetothereaction of dissolved sulphur with lithium anode. As a result, the low-order polysulfide will diffuse back to the cathode to create high-order polysulfides. Hence, diffusion back and forward of a different order of polysulfidesbetweentheanodeand cathode will occur continuously because of the shuttle effect (figure 1). To overcome these difficulties in each system, a primary requirement is to develop structurally stable electrode materials with good physical and electrochemical properties.

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TREADING WATER
Chemistry

Metal-organicframeworks (MOFs) actasanovelclassofporous materialswithpossible“postsyntheticmodifications” withthepotentialin numerouschemical applications.MOFsare composedofsecondary inorganicunits:“nodes” andorganic“linkers”. Structurally,thenodesare metalionsorclusters coordinatedmainlythrough nitrogenoroxygenatoms. Interestingly,thesematerials provedtheirpotentialover otherporoussolids(suchaszeolites, byconsiderablylargerporesizeand volumes).Therefore,whilemerely stericallyunhinderedsmallmolecules fittheporesinzeolites,MOFspossess theadvantagefor selective catalysis reactionswithmore bulky compounds.Intermsofvariationsof themetalcentre,suchasby substitutionofsecondaryorganic unitswithanidenticallinker,yield variousgeometricdifferencesinMOFs (figure2).Thegeometricalterationin MOFsdependsonthearrangementof thelinkersubstituentswhichis followedbyachangeinsymmetry andporesize.

In polysulfide encapsulation, the ability to control porosity and chemical environment in MOFs directlyimpactstheelectrochemical process. Their varying pore geometries facilitate ion diffusion, which is essential for fast discharging/charging processes. When applied to Lithium-sulphur batteries, MOFs can store the large expansionofsulphuruponreduction to Li2S. One of the significant drawbacksintheutilisationofMOFs for LSBs batteries is the poor electrical conductivity which leads to slow redox kinetics, poor rate capabilities,andcyclingstability.

InarecentpromisingstudybyJiang et al. (2018), a combination of conductive polymers and MOFs was used to construct polypyrrole-MOF (ppy-MOF), which resulted in significant charge-discharge rates: 1,685 mA g-1. Variation of porosity geometry affected ion diffusion, in which cross-linked pores and tunnel MOFs exhibited the best high-rate performance with a maximum specificcapacity of790mAhg-1.In terms of chemical properties, frameworks with coordinating unsaturated metal ions increase the adsorptionofpolysulfideanionsdue totheirnegativechargesandfurther stabilisation of sulphur-MOF interactionsbytheorganiclinkers.As investigatedbyParketal.(2018),the use of nMOF-867-based electrodes significantly increased capacity retention with little loss observed. The potential in MOFs electrochemical properties can be further investigated using LithiumOxygen batteries, Sodium-Ion batteries, and even as battery separators.

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Chemistry
Fig 1. A schematic illustration of the “shuttle effect”.Atransitionbetweensolid-liquid-solid state occurs between Sulphur species in Li-S batteries(Renetal.,2019)

While researchers are extensively searching for new renewable, sustainable forms of energy, one of themostfundamentalandpromising renewable sources is sunlight During photosynthesis, plants store solar energy in chemical bonds using H2O and CO2. The stored energycanbeeasilyaccessedatany time, yielding the advantage of replicating photosynthesis for largescalesolarenergy.

Artificial photosynthesis is a large area of research that couples the oxidationofwaterwiththereduction of carbon. It faces many challenges, with a major difficulty in the chemistry of splitting water moleculesintoH2andO2.Oneofthe early examples of artificial photosynthetic assemblies includes dye-sensitised photoelectrochemical cells (DSPECs). The mechanism involves thecouplingofmetaloxides:p-NiO, n-TiO2 with molecular catalysts to oxidisewaterandprotonreductions. However, while the hybrid system managed to generate solar energy successfully, the difficulty of translatingtheprocessintodailylife technology remained with various limitations:stabilitytolightandpH, selectivity and efficiency, and highvalueproducts.

SCIENCEMIND WINTER 2023
Chemistry
Fig 2. Various geometries in MOF upon reactions of different metal ions with a similar organic linker terephthalate (BDC) dianion. The general shape of the core cluster is a consequence of the spatial arrangement of carbon atoms. The coordination number (CN) refers to the number of linkers coordinatingtoeachcluster(Butovaetal.,2016)

MOFs seem to be a promising solution for artificial photosynthesis. Theporosityiscrucialasreactionsin artificialphotosynthesisinvolve small molecules: CO2 and H2O as substrates, and O2, H2, and CO as products.Intermsofmasstransport inMOFs,thediffusionmodelisdriven by a concentration gradient, and small molecules can readily diffuse through the framework. In contrast, larger molecules diffuse slower with lower penetrations to the interior of the framework. While larger pores might improve mass transport into the framework, they might not be efficient enough to overcome diffusion barriers when considering diffusion rates through them. Therefore,thenatureof solvent-MOF interactions influences diffusion control and is critical for mass transport in artificial photosynthetic processes. For an effective artificial photosynthesis catalysis, it is crucial for the catalyst to be efficient towards the reactants and selective for the product. Interestingly, MOFs can be highly selective for CO2 reduction catalysis with small pores providing uniform adsorption sites and effectively boosting local concentrations of key reactants/intermediates.

While various modifications of MOFs show a range of promising applicationsinthenovelpreparation of Lithium-based batteries and energy storage, more research is neededtoimprovethecurrentstate of knowledge and understanding of these porous materials for future generation applications in artificial photosynthesis and cutting-edge heterogeneouscatalysis

REFERENCES

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WINTER 2023

Mycelia: a promising lead to the ecological revolution

Today,theastonishingpropertiesof mushrooms,whichholdaninvisiblelibraryof useswhichgofarbeyondthesphereoffood,havepiquedtheinterestofamultitude ofstart-ups,eachbettingontheuseoffungiwithinour health industrybutalsofor biostimulants, biofuels and biomaterials

GiantNaturalOrganisms

Thefungaluniverseisutterlyexpansive and intriguing to many scientists, considering we are just “barely beginningtounderstandthecomplexity and the degree of fungal sophistication”, underlines biologist Merlin Sheldrake in his bestseller Entangled World¹. Not only, but fungal applications could potentially bring a multitude of bio-sourced solutions to many of Earth’s urgent environmental problems². Commonly referred to as "mushrooms", the latter is in fact the onlyreproductiveorgansresponsiblefor dispersing the spores of a much more extensive and invisible filamentary entity: mycelium

Those convinced that blue whales or redwood trees are the largest living organisms on the planet will be surprised to learn they’re wrong. As of this year, a mushroom within the Armillaria Gallica family whose mycelium extends over 9 km2 and weighs nearly 400 tons, has been found in Oregon³. Similarly, a boletus mushroomcancoverupto 100m2

Thus, fungi are forced to feed at the expense of another organism and have therefore forged a strategic alliance with most plants on the planet². Mycelium filaments are additionally grafted onto their rootlets, sometimes going so far as to enter their cells and considerablyextendingtheirnetworkof roots; a phenomenon known as “mycorrhization”.

A perfect example of symbiotic interdependence that has shaped our world is the exchange of mineral elementsthatarepumpedfromthesoil and transmitted to fungi’s hosts, providing the fungi with sugars produced by photosynthesis. In return, itisbelievedthatfungiallowedrootless algae to colonise our soil over 400 million yearsago!

TheMoldyPhenomenon

Edibleornot,macro-mushroomsfound within woods represent only a small portion of the fungi kingdom of life¹. Over 80% of mushrooms do not bear fruitandanevenlargernumbercannot spreadtheirmyceliumoverlargeareas of land, like the boletus mushroom, morecommonlylivingonamicroscopic whilstsimultaneouslygiving dozensoffruitingbodieswith helpofitshyphae.

Mycelium’sprofusionoffilaments canbeexplainedbya mushroom’sinabilityto synthesiselightandfeed itself.

scale.Moreover,notall fungibasetheirsurvival onmycorrhization,rather havingadaptedtofeedon othersubstrates².Specimens ofthesaprotrophsfamily containenzymesthatare

TREADING WATER Biology
| 31 SCIENCEMIND WINTER 2023

able to decompose the lignin and cellulose of trees, thriving in particular on dead tree trunks or other forms of biomass. Without these fungi, forests and natural fields would be covered with bio-waste, thus preventing soil regeneration. Also within this family exist several excellent edible specimens, such as oyster or shiitake mushrooms. Conversely, other forms of mushroomshavefoundthatinorderto satisfy their voracious appetites, they mustbecome pathogenic;in otherwords,killingtheirhost anddevouringthelatter.

Formostofhuman civilisation,we never understood themechanisms behind moulds, yetwestilllearnedhowto domesticate thesestrange organisms¹.Ourbodiesareno exceptionto fungalcolonisation, withtheirabilitytohostan abundanceofthese microscopicentities,suchas fungusfromthe Malassezia globosa familywhich degradesthelipidfilmofour scalp(i.e.theappearanceof dandruff)orthose contributingtothe properfunctioningof ourintestinal microbiota.There existsauniverseof polymorphicorganisms providinguswithavaluable ecosystem ofservices,whose potentialpropertiesandapplications arejustbeginningtobediscovered;itis suspectedthatonly100,000outofan estimated 5million strainshavebeen listedanddescribed³.

Eco-ResponsibleSoil Decontamination

Assisting soil de-pollution, certain fungi, such as oyster mushrooms, contain enzymes capable of degrading harmful hydrocarbons¹. Certain companies have achieved successful excavated soil clean-up by coating mushroom spores with algae to better guarantee fungal preservation. Others have developed a way to produce bioethanol from biomass waste during aprocessknownas fermentation using

Trichodermareesei,a particularfunguswhich secretesenzymes responsibleforthe metabolisationof celluloseintosugars. Thismicroscopicorganism wasfirstdiscoveredbyUSArmy scientistsduringWorldWarIIinthe SolomonIslands,whereby researcherssoughtto identifythecause oftherapidrotting ofuniforms².

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Biology

The current lineup of new, innovative mushroom-based materials has proved the fungal world’s extremely promising future, provoking the question of how best to exploit mycelium’s growth capacity, whose envelope is made up of chitin, an organic substance found within an insect’sshellwithpropertiessimilarto that of cellulose⁴. By mixing together agricultural waste-type biomass sawdust with mushroom spores in a mould, one can grow a compact and compostable biosourced-material capableoftakingonanyforminjusta fewdays,requiringvirtuallynoenergy expenditure. Nonetheless, the productioncostsarestill much higher compared to the polystyrene (plastic) thatdominatesthemassmarket.

Myco-Health,HomesandLeather

Recently, a whole string of small businesses has begun exploring the distantoriginsofmushrooms,including their health benefits, though it is believed the mentioned have been a part of traditional pharmacopoeia in Asiafor nearly three millennia.Inthe West,interestdevelopedmuchlater,in particular with respect to Alexander Fleming, who managed to isolate penicillin from a fungus back in 1928, givingbirthtothefirstantibiotic¹.From immunosuppressive cyclosporine to cholesterol inhibitor statins to psychiatric psilocybin, certain active moleculescontainedwithinmushrooms haveenteredtheworldofmedicineto helporchestratetheproperfunctioning ofthe immune, digestive and nervous systems alike.

Mycelium’s manufacturing process has alsobeenappliedtotheproductionof other alternative materials, such as concrete blocks. This not only applies to homes on Earth but potentially offEarthdwellingson Mars andthe Moon⁶ Insteadofmetalorglasshousings,the currentmoderneraofgreentechnology has prompted NASA’s Ames Research Center to invest its time in developing prototype containers made using the invisible underground threads that makeupmycelium.Theobjectiveofthis projectistoultimatelyallowindividuals to be able to independently cultivate their own habitats using lighter materials.

DownonEarthandcombiningin-depth science with haute couture design, garments were recently launched by StellaMcCartney,showcasingthisnextgeneration material’s fullest potential andpavingthewayfornumerousfuture commercial offerings. In the midst of the Covid pandemic back in October 2020,StellaMcCartneyexploredtheuse of Mylo™ material, providing critical feedback and ultimately becoming a part of the exclusive consortium of brandsworkingalongsidethemycelium BoldThreads team⁷. The earliest two garments announced by McCartney includeablackstraplesstopandutility pants: both unique, cruelty-free and effortlessly sensual. The pieces have been meticulously handcrafted in McCartney’s London workshop using panels of mycelium-based material, whicharethenlaidatoprecyclednylon.

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Biology

McCartneyandBoltThreadshavebeen partners in sustainable innovation since2017,theStellaMcCartneyluxury brandtakingpartintheMylo™journey sinceitsgranddebut.Infact,thefirst product ever created using Mylo™ products was a prototype of Stella's iconicFalabellabag.Thisstate-of-theartdesignprocessis non-petroleumbased, stipulating the remainder of moreundergroundfossilfuelsandless spilledplastic.Consequently,Mylo™is fabricated to have an extremely minimal environmental impact and takes just several days, rather than years,tofabricate.

Creating new, high-quality biomaterials isamajortechnological challengeandahugeopportunityfor both people and the planet. The materialusedinherfirsttwogarments not only represents a huge step forward for the aesthetics of biomaterialsbutalsomarkstherollout initiation of the ready-to-use Mylo™ product. This is a tangible progress towards an eventual large-scale production where Mylo™ has a significantly positive impact on our planet.

Earth’s Surprisingly Indispensable VegetativeStructure

To close, mycelia showcase an essential role within terrestrial and aquatic ecosystems bybreakingdown and converting plant matter into assimilable nutrients, not only in an unassistedfashionbutalsowithaidof other plants and subterranean life forms⁶. In addition, mycelia promote the organic composition of the soil, their growth also giving rise to atmospheric carbon dioxide and promoting water and nutrient absorption from plants around or in symbiosiswiththem.Notonlythis,but mycelia hold the capacity to protect plants against certain pathogens that attack their root systems. In short, mycelium is used to feed many invertebrates found in the soil and is thus required for a functioning agricultural system and for the survivalofmostplants ontheplanet.

References

34 | SCIENCEMIND WINTER 2023
Biology

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