Dear Chelsea

 I’m sure nobody can even view this blog anymore, but maybe like a message in a bottle it’ll find its way to you. I wish I’d been brave enough to say hi when we passed in the hall at RVC a few years ago. I tried to finish my BSc but despite the support of a wonderful friend group I didn’t have it in me after year 2. I dropped out and drifted aimlessly for a while until I got a job caring for dogs. It’s not exactly a STEM field but it’s fulfilling. I really hope you found a career you enjoy doing. 

I’m so grateful you got me into Magic! I still play Commander every week at Dark Sphere in Shepherd’s Bush, and I’ve met so many wonderful people through it. I also still play Guild Wars quite a lot, and got really into raiding last year. Do you still play? 

It’s been so long since we last spoke, maybe the version of you I knew doesn’t exist anymore. Maybe the version of me you knew doesn’t exist anymore? Regardless, I miss you and would love to catch up.

Love, 

Niamh 

Our 'La La Land'

Musicals aren't usually a genre of film that capture my attention, or hold it for that matter. However, I somehow ended up seeing 'La La Land', and it struck such a chord with me that I am writing this as I leave the theatre. In some weird twist of what some may call fate, life threw at me a movie I needed to see, and a perspective that I had never considered. Perhaps one day, five years from now, we'll catch each-other's gaze across a crowded room, and think of what could have been. Everything else will fade away as I stare into your eyes, and see us navigating the treacherous ocean of life together, as though we were never apart. Maybe then I'll be able to smile at you, and think to myself that it was all worth it. "I always loved you".

'Junk' DNA vs The World 2

Looking over the skyline of Camden as the sun sets on my first day of university life, I begin to to contemplate my place in our world. How much impact could I ever make? I am one average person in virtual sea of more prolific people, all trying to find meaning in an existence that intrinsically has none (I blame the Satorl Marsh night theme I'm listening to for that last bit). But my existential crisis aside, I did begin to think about the human genome, and how the neglected 'junk' elements of it must feel, always being in the shadow of the protein coding genes, which have a reputation as the be all and end all of molecular biology. Although personifying genetic material is not really a valid way to think about the issue... Therefore I will once again champion the Junk DNA in its quest for genomic appreciation. As I stated last time, human proteins are often the same size as equivalent proteins in simpler organisms; it is the sections of intervening junk that increase in size as the complexity of an organism increases. This creates what Nessa Carey describes as a large 'signal-to-noise ratio' during analysis of genes within our genome, as there's only a relatively small region that codes for protein, embedded in a large section of junk. But this DNA must have a role to play, otherwise we would be no more complex than a fly or a worm... (only a slight exaggeration...) Some complexity is added by post transcriptional modification of mRNA, in a process known as splicing. In splicing the exons, sections of DNA which code for proteins, are cut away from the intron sequences (the junk), and can be arranged in various fashions to generate different mRNA molecules from the same gene. Over 60% of human genes produce multiple splicing variants, however this only goes so far in explaining our relative complexity. Back in 2001, in the wake of the Human Genome Project, researchers thought the junk may not even have a functional role, as the pufferfish Fugu rubripes has a genome 13% the length of our own (devoid of much of the junk we see in our genomes), and is still a successful organism. It was hypothesised that the junk was parasitic, selfish DNA using our DNA as host for future proliferation (I just can't escape you Richard...). Although based on what we know about evolution, it is irrational to assume that just because the DNA has no obvious function in one organism, it does not mean it is useless in all organisms (especially in more complex species). One theory supporting the importance of junk DNA states that it could act as mutation insulation for the protein coding genes, as it makes it decreases the likelihood that a point mutation will affect a protein coding sequence, a benefit of the large 'signal-to-noise ratio'. The reason humans would need more mutation insulation than simpler organisms is because we have longer life spans, and therefore we accumulate more mutations, and we also produce fewer offspring, so it is beneficial that they are better protected from mutations in order to ensure species survival. In terms of cost-benefit, it isn't worth expending resources in simpler organisms to protect protein coding genes, as even if they accumulate a mutation they are still viable (fewer systems can be affected by the lack of protein production), and the offspring will likely still survive and breed (ah the virtues of simplicity). So who's irrelevant now 2001 geneticists? But seriously, if the junk DNA is used as a buffer for mutations, which have the potential to disrupt vital metabolic processes for example, is the nomenclature 'junk' still applicable? Not in my book, and this is my blog. Deal with it. How empirical of me.

'Junk' DNA vs The World

Proteins, proteins, proteins; Biologists are obsessed with them. Sure they are the reason us complex organisms can exist, but as a result of this infatuation with our polypeptide friends, we often overlook a rather important aspect of the human genome. Only 2% of our genome codes for proteins, and so until recently a large proportion of the other 98% was dismissed as 'junk' DNA. However, we are now realising that proteins may be the final end points required for life, but they could never be properly synthesised and organised without the junk genetic material. In fact, research into the genomic differences between more complex and simple organisms has concluded that the only genetic change that occurs as biological complexity increases is a greater percentage of DNA that does not code for proteins. Junk DNA can code for RNA, not the mRNA that is used for translation of proteins, but RNA that is functional in its own right! (more on this later) I personally feel betrayed by the A-Level Biology syllabus at this point... Anyway, the fact that Biologists were so focussed on the effect mutations had on protein coding DNA, meant that they were looking in the wrong neighbourhood of the human genome for the cause of inherited disorders like myotonic dystrophy. Within the myotonic dystrophy gene, a small base sequence (CTG) is repeated multiple times; 5-30 repeats in a healthy person. If the number of repeats exceeds 35, the sequence becomes unstable and can change in number erratically from one generation to the next, and as the the length increases generationally, the symptoms of the condition worsen, and develop earlier. At this point you're probably thinking; this is just a standard change in the base sequence of the gene, inhibiting the production of the correct protein. However, you would be wrong, as the amino acid sequence produced by this mutated myotonic dystrophy gene is unchanged, and the protein is still synthesised (did I just hear the jaws of the uninitiated drop?). Is this just an anomaly perhaps? Certainly not. Fragile X syndrome, the most common inherited learning disability, and Friedrich's ataxia, a muscle wasting disease, follow a similar mechanism. This was an unnerving revelation for researchers; there are mutations that can cause disease without changing the amino acid sequence of proteins. But in that case how do sufferers develop such debilitating symptoms? In Friedrich's ataxia, much like in myotonic dystrophy, the abnormally large section of repeats (GAA in the case of FA) is found between 2 sections of the protein coding genetic material(so in the junk DNA). Research has shown that when cells contained the expanded repeat, the production of mRNA encoded for by the gene was inhibited. The enlarged section of GAA repeats prevents accurate copying of the DNA, and thus there is no translation. In the case of Fragile X syndrome this means RNA around the cell is not properly regulated by Fragile X protein, causing cellular chaos and a life of disability for the sufferer. But that begs the question; why have the repeat sequences within the genes for myotonic dystrophy for example, been conserved over our genomic evolution? I mean, the repeats are located at the very end of the gene, so could easily be left out of any RNA produced. This means they must have a purpose in a healthy cell, within the mRNA of the gene. This is in fact the case, as the myotonic dystrophy mRNA is used to bind proteins in the cell (a weird role for mRNA), and the larger the repeat expansion, the more molecules are bound. The proteins are normally involved in the regulation of other mRNAs; controlling their lifespan and translation efficiency, and so without these regulatory polypeptides, the cell cannot function correctly. This discovery made sense to clinicians, as diseases in which a small change in gene expression creates such a huge impact on a patient, with fine tuning of severity between patients (based on length of repeats), are simply not observed. Therefore the role of this mutated junk DNA is more complex than we first thought, as it is not simply the number of abnormal repeats within the DNA that affects symptoms, but also the role of the expanded section of repeats on the mRNA synthesised from the mutated section of DNA in gene expression. From this paradigm it is clear that the fact that we have sequenced the human genome does not mean we understand all of its intricacies. Junk DNA has a powerful role, not just in inherited diseases, but in almost every aspect of our genome, and even our epigenome. That is why I'm so excited to continue this series, shedding light on the enigmatic sections of the genome previously condemned as insignificant junk.

The rise of the 'Dino-Chickens'

The first Archaeopteryx fossil was unearthed from a limestone quarry in Bavaria, in the early 1860s. This relatively small (Raven size as an adult), feathered, broad winged dinosaur is believed to have glided like a bird through the forests of the Jurassic period 145 million years ago, leading many palaeontologists name it the ancestor of modern birds. Phylogenetic study is never so clean-cut however. Therefore it is unsurprising that other species similar to archaeopteryx; Aurornis xui, and the four winged Anchiornis huxleyi for example, are also contenders for the title of the first bird. But why are our winged dinosaur friends relevant? Well in May 2015 scientists were able to 'alter' chicken embryos to produce a dinosaur-like snout, which was an amazing breakthrough given the lack of clarity in the evolution of dinosaurs into birds; there is no single physical feature that defines this phylogenetic change. One important phenotypical transition evidenced by fossils was the alteration of the premaxilliae in the reptilian snout, growing longer and fusing together to form the beak structure present in birds today. The research team from Harvard then looked at gene expression domains in the face of multiple bird and reptile species; the earlier frontonasal ectodermal zone (FEZ) and the later midfacial WNT-responsive region (they sound incredibly intellectual but rather arbitrary at the same time). From this the researchers reasoned that reptile and dinosaur snouts develop from premaxillae in a similar way, and that the developmental pathways that form the snout were altered in the course of the evolution of Aves. 2 proteins; FGF and Wnt, were found to be essential in the differing developmental process of reptile and bird faces, due to differential gene expression and therefore differential translation of these proteins. The proteins worked differently also, as in reptiles they were active across 2 small regions of the embryo's 'face', whereas in birds they were expressed across a larger band, but in the same region as in reptiles. This may be evidence that evolutionary alteration of expression of these proteins contributed to beak formation. To test this theory and the mechanism of the snout to beak transformation, the autapomorphic median gene expression region found in birds (the area of the genome coding for the beak) was altered in developing chicken embryos. Biochemical inhibitors were added to the chicken eggs to block the 2 vital proteins, thus reverting the chicken's beak to its ancestral reptilian snout, with the premaxillae formed showing a resemblance to fossil specimens, rather than beaked birds. If you're like me though, the term 'biochemical inhibitors' is far too vague. So what do they do exactly? I believe they alter the epigenome of the chicken embryo, perhaps removing methyl groups from CpG regions of long silenced genes, or they may involve acylation of the tails of histones (perhaps using histone acetyltransferase enzymes) to alter transcription rates of genes (See my previous posts for more on epigenetics, it's my favourite thing ever). Back on the Dino-Chickens; let's not get overexcited about a potential Jurassic World situation happening where we reverse engineer dinosaurs and splice them all together into ridiculously improbable 'combosaurs'. The team from Harvard was only seeking the mechanism behind ancestral amniote snout transformation. But perhaps in the future... My army of squid, poison dart frog, chameleon ankylosaurs will become a reality!

Zombie Apocalypse anyone?

"Brains..." That is what most of us Western World dwellers think of when the topic of the undead is broached, however most of us are clueless as to the origin story of our beloved halloween staple; the Zombie. I would like to dispel this ignorance, but at the same time give a real world example of where zombification (It's a word now, deal with it) is an all too real occurrence, but also how it can even happen. Our story begins in Haiti, where rural folklore describes necromancers, who supposedly used magic to commune with or summon the dead, and had possibly the most epic job title ever. These Zombies would become mind-slaves of the necromancers (but they were not called Steve weirdly), and had no will of their own. The root of such folklore lies in Africa, and was likely exported to Haiti via slavery. The African slaves believed that Vodou deities would resurrect them and take them to the heavenly afterlife in their home continent. Western Zombies just seem uncultured and dull compared to the Haitian legends, you might say they pale in comparison... (I'm not entirely sure that made sense). That's enough history for today, let's get our biology on! The real world Zombie-esque paradigm we shall confront involves the sophisticated predator that is the Ladybird, and a wasp of a parasitic persuasion. Did you know Ladybirds use their antennae to detect chemicals that plants release when under attack by herbivorous insects like aphids (the Ladybird's main prey), and they can bleed poison from their legs to dissuade predators? The fact that they are so effective within their niche was why it came as a shock to me that they are vulnerable to zombification. The parasitic wasp in question, Dinocampus coccinellae, uses its stinger to inject an egg into the Ladybird's underside, along with a venom. Once the larva emerges, it feeds on the fluids that fill the Ladybug's thorax cavity. Externally, the insect is still behaving normally, eating aphids with its usual fervour, which in turn feeds the parasite growing within it. This is where it starts to get upsetting, so please if you have a weak heart or a particularly irrational attachment to the Ladybird, stop reading now. After 3 weeks of 'gestation', the larva squirms out through a weakness in the Ladybird's exoskeleton, and creates a silk cocoon for itself below its host. The Ladybird remains under the control of the parasite though, and so stays perfectly still during this process, apart from when the wasp larva's predators approach. The Ladybird acts as an insect shield for the D. Coccinellae by spasming its limbs to scare off Lacewing larvae for example. This continues for a week, until the adult wasp cuts itself free of the cocoon with newly formed mandibles and flies away, finally deigning its enslaved protector to die... But why did such mind controlling, zombie-making parasites even come to evolve? The answer, like just about everything on this blog, lies within the genome of the organisms. Genes use organisms as vehicles to increase their own replication success, and the phenotype created by the genes is vital in this process. The phenotype is not just limited to dictating the appearance of an organism. It can profoundly alter the organism's environment, as the phenotype extends to structures in the brain which produce specific behaviours. So if a gene is powerful enough to alter a physical environment, then could it manipulate another living creature? The fact that parasites can manipulate their hosts is because of transcription of genes and resultant translation into necessary proteins, and if a mutation changes the base structure of the genome, the way in which the parasite influences its host's behaviour will change, and those parasites that produce the most offspring have developed a mutation that changes the host's behaviour in a favourable way. For example the parasitic wasp genome that codes for venom molecules that cause the Ladybird to act as a bodyguard for the growing larva will be more successful, and so the genes which dictate this will be found in higher frequencies in offspring and therefore in the gene pool of the species as a whole. In this way the need for genes to preserve themselves and increase their chances of wider replication affects the behaviour of another organism... So there you have it; the genetics behind the development of such extra-ordinary mind controlling (zombifying) powers. It was never necromancy, just egomaniacal genes. Biology wins over popular culture and mythology once again! (In my head at least)

The hardiest bear that never was

Just over a month ago I visited the American Museum of Natural History in New York City. There I was fascinated with the phylogenetically accurate layout of fossils over the museum floorspace, showing the evolution of fish to amphibians, and then to reptiles (no Tiktaalik unfortunately) for example. During my visit I was also enraptured by an exhibition entitled; Life at the limits: Stories of Amazing Species, as one particular species stood out to me as the star of the survival show.
What if I told you there is a species of 'bear' that has existed on earth since the Cambrian period, around 500 million years ago? The word delusional would most probably spring to your mind, however I have evidence from the fossil record. Perhaps the word 'bear' was disconcerting, as I did not mean a member of the Ursidae family, but in fact a species known as the Tardigrade (me and my science word plays...). The Tardigrades have nicknames such as Water Bears or Moss Piglets, perhaps due to physical appearance (I don't see it personally, but they are kinda pudgy) and their favoured habitats; films of water that cling to mosses. Tardigrades are a large group of animals, consisting of 1,150 species, that includes some of the toughest creatures in the world. They can be found the world over; from the Himalayas 20,000 ft above sea level, to the deep sea 13,000 ft below sea level, even in the polar regions and on the equator, where the environment is hardly accommodating. Although I wouldn't hold out any hope of seeing one with the naked eye, as most individuals range from 0.3 to 0.5mm long. The Natural History Museum exhibit depicted the survival abilities of these organisms as a cycle, which I thought worked rater effectively. First, when their surroundings become intolerable, certain species of Tardigrade are able to deflate, draw in their legs and coat themselves in a waxy substance. The resulting structure is called a tun, and is barrel-like in shape with the creature's claws protruding from it. In this state tardigrades are capable of reversibly suspending their metabolism in cryptobiosis, and many members of the species can regularly survive in this state for up to 10 years. At extremely low temperatures, the Water Bear's body can go from 85% water to just 3%, ensuring they are not ripped apart by the water in their bodies expanding during freezing. When re-hydrated, it can take as little as 4 minutes for the animal to bounce back from its near-death state. Natural selection has seemingly thought of every extreme environmental condition on earth; the harshest pressure (they can survive in close to vacuums), temperature, radiation (5,000gy of gamma rays compared to the lethal dose of 5-10gy for humans), dehydration and environmental toxins. Certain species can even survive in outer space! (slight sensationalism), and in my view they truly earn their title of extremophiles. Science has so much to learn from such a tiny animal, particularly the proteins they produce to protect their cells from apoptosis during dehydration. (this seems to be a theme of my blog now), and even if humankind never make inter-planetary colonisation a reality, the Tardigrade is an excellent candidate to be our intergalactic envoy.

Pleasure, Psychoactives and a Basement...

This is a post I've been meaning to write for quite a while, but other exciting biological concepts got in the way. Story of this blog. The title is perhaps misleading, as it implies some kind of lugubrious activity, however the topic at hand is rather removed from such criminality, at least I hope. The lecture was titled; Pleasure, Novel Psychoactives  and the Brain's Basement (see, I wasn't lying about the basement) and was lead by Professor Gaetano Di Chiara of the University of Cagliari's Pharmacology department. The main body of the lecture revolved around the brain's response to psychoactive drugs, and the various experimental methods used to investigate the mechanisms behind the response. Professor Di Chiara was clearly passionate about his field of study, and so he went through the slides of the presentation at an astounding rate. This, combined with his somewhat broken English lead to my notes becoming rather scant at times, but despite this I would like to share what I was able to glean. Firstly, the definition of pleasure used by the Professor and his team; incentive to seek and accept biological incentives (food rewards for example). There are 2 distinctions of pleasure; Appetitive, which is preparatory and so comes from learned stimuli, and Consummatory, which is caused by proximal stimuli, and is unconditioned. The neurotransmitter Dopamine is widely believed to be responsible for the pleasure response of the brain, and is therefore connected to rewarding stimuli, which often aid in the survival of a species (feeding, reproduction etc). Addictive drugs also trigger dopamine release, as when a micro-dialysis tube is used to measure neurotransmission in the ventral striatum of the brain, psychoactive drugs produce a lasting spike in dopamine levels.  These ventral areas, around the amygdala of the brain, are phylogenetically the older areas of the mammalian brain, and are therefore referred to as the brain basement (just to clarify the lecture title). One fact that is, according to the lecture, contentious within the scientific community, or was contentious about 10 years ago, when most of this research was conducted, but also the last time Professor Di Chiara kept up with developments in this area of study (burn) (He referred to the archistriatum of the brain, which only exist in birds and are now called the Arcopallium; it's homologus to the amygdala im mammals essentially) is whether the biological function of dopamine is purely pleasure, or whether it has a motivatory function in survival of organisms. Rats are often the subjects of addiction experiments, and the Master/Yolked experimental paradigms are no different. The 'Master' rats were in a set-up which allowed them to actively expose themselves to the drug heroin, whereas the 'Yolked' (not quite sure about that nomenclature there) rats were passively being administered the drug. It was observed that Master rats experienced a greater dopamine output  in the shell of the nucleus accumbens (part of the ventral striatum), which is involved in the cognitive processing of wanting as well as reward and reinforcement effects. On the other hand the Yolked rats' response non-contingent drug exposure (I hope that's a thing) saw a a smaller increase in dopamine output in the core of the nucleus accumbens, dealing with new motor programs which facilitate the acquisition of a given reward in the future. This suggests that the master rats experienced a heightened euphoria on drug exposure, but why is this? I hear you mumble sleepily... I'm so glad you asked. The fact that the master rat group were self administering the drug was the key, as they were able to predict and therefore better cope with the side effects of the drug, something the passively drugged yolked rats were unable to do, thus prolonging the heroin high. The master rats would eventually have the conditioned stimulus of administering the drug completely replace the primary stimulus of the heroin itself. The drug essentially triggers no dopamine release, and so the IV self-administration becomes the main source, as the user has habituated to the drug. By extension of this paradigm researchers were able to link drugs of abuse with increased extracellular dopamine secretion in the accumbens shell particularly, clearly displaying dopamine's ability to promote expression of incentive-based motivation, in a Pavlovian manner. In my mind I have ended the debate; dopamine is a biological motivation tool, which can all too easily lead to dependance on unsavoury activities to achieve a pleasure sensation. So please, put the needle down...

More powerful than Aquaman? Impossible.

Fancy seeing me here, on my own blog... Anyway, of late I have been enraptured by the Reckoners series of novels by a hero of mine, Brandon Sanderson. The series thus far tells of ordinary humans being transformed into super-humans, with an immense spectrum of powers, by a deity/celestial body known as Calamity. In the Reckoners universe such super-humans are known as Epics, and their powers corrupt them to such a degree that they have fractured society and created a nightmarish dystopia. This got me thinking, if Epics had dominion over ultra-specific biological processes, would they be stronger than the fictional  superheroes we have bombarded at our retinas every time we go to the cinema? Thor may have Mjolnir, and Bruce Banner may be able to turn into a green thug when his heart rate spikes, but those powers have nothing over the total control of AXOPLASMIC STREAMING (long context is very long). Axoplasmic streaming is the process responsible for the movement of proteins, lipids, mitochondria and other organelles to and from the cell body of a neurone. An example of when this mechanism is relevant is in the synthesis of neurotransmitters and synaptic vesicles in the cell body of motor or sensory neurones, which must then be transported to the synaptic knob (eloquent I know) for the propagation of action potentials across the synaptic cleft. Microtubules, much akin to those that construct the cytoskeleton in your average Joe body cell (all cells are amazing I merely jest), made of the globular subunit tubulin, create the pathways for movement along the axon to the synapse, and 2 vital motor proteins; dynein and kinesin, are used as haulage vehicles for everything synthesised by the Nissl's granules in neuronal cell bodies. The speed of axoplasmic streaming is variable, something I found particularly interesting with regard to my super-human powers investigation. The speed is dependant on the cargo of the motor proteins, with vesicular cargo moving far faster at up to 400mm/day, than other proteins; for example cytoskeleton proteins move as slow as 8mm/day. To clarify, the Epic with this power over Axoplasmic streaming would not manipulate his/her own process.  That would have no biological benefits as the mechanism has been optimised by millions of years of evolution. The Epic would manipulate the streaming in other people, making it a weapon of sorts. By slowing down the streaming of synaptic vesicles and the neurotransmitters within them along the axon to the synaptic knob, less neurotransmitter (acetylcholine for example) would be available for release into the synaptic cleft when an impulse reaches the pre-synaptic membrane, essentially halting the progress of the action potential, due to the reduced permeability of the post synaptic membrane to sodium and potassium ions (acetylcholine binding there increases permeability to ions). This would  create a kind of rapidly induced accommodation effect in the neurone, causing paralysis of muscles comparable to that induced by the botulinum toxin, which inhibits the binding of acetylcholine. So my hypothetical Epic power would allow the wielder to kill a person with spectacular efficacy, just by having dominion over one relatively esoteric, yet vital biological process. In fact, if the wielder could create a wave of axoplasmic manipulation, they could kill in vast volumes over a minuscule time period. Who needs a high-tech suit or the powers of a Norse God, when you can disrupt the highly complex interplay of biological molecules in the nervous system? This Biologist certainly doesn't (therein lies my bias...).

Steve the telomere

Hello fellow biologists and apparently Zach too! I'm back after what seems like an eternal sabbatical, and it must have seemed longer for you guys, because I know how much you love reading my random and often overly opinionated thoughts on biological processes. Doing 4 A-levels is tough ok, and the majority of the school Biology syllabus is so dull. More epidemiology or epigenetic mechanisms are required please Edexcel. Anyways, today I'm going to tell you guys a story, with a biological twist. Once upon a time, in a nucleus far, far away there lived a chromosome. This chromosome was young and healthy, no mutations or replication errors, just enjoying life in the nucleolus, surrounded by friendly histones and its other chromosomal buddies. But what keeps our young chromosome friend mutation free? you may ask. Telomeres, my dear Wattson (I know that doesn't work, just humor me). Telomeres are areas of repeated nucleotide sequences, TTAGGG repeated 2,500 times in humans, at the the end of each chromatid on a chromosome, which protect the chromosome from potential mutations, as well as stopping neighboring chromosomes or fragments from randomly fusing with each other (they're such a friendly bunch). Due to the nature of semi-conservative DNA replication in eukaryotic organisms, the ends of the chromatids cannot be copied by DNA polymerase, and so instead of the base sequence being ruined by this flaw in our DNA replication mechanism, the telomeres are there to valiantly defend the chromosome from damage. I may be romanticising slightly here, but I can't stress enough how valuable telomeres are to our genome. After 'taking one for the team' so to speak, an enzyme called telomerase, a reverse transcriptase kind of enzyme, synthesises new repeating sequences to replenish the telomere 'cap' on the chromatids, so they can continue to protect the chromosome from damage. At this point you would be forgiven for thinking that, if we could maintain the telomeres in our multipotent bone marrow (hematopoietic if you're a sucker for the biological terminology like me) stem cells for example, we could extend our lifespans. But actually, telomere shortening in cellular senescence (biological word for aging) is an essential process in the reduction of cancer risk, we think. Telomere shortening in humans can induce replicative senescence, a mechanism which prevents instability within our genetic material and thus the development of cancer in the older body cells produced, by limiting the number of cell divisions they can undergo before apoptosis. However, shortened telomeres can also impair the immune system, and that might increase cancer susceptibility. The telomere shortening process is the very definition of a double edged sword, as it may protect our most vital genetic information from the corruption of cancer, but it is also the root of just about every age-related disease you can think of. So next time you're having an existential crisis about your place in the universe, remember that Steve the telomere has always got your back.

The biological supercomputer? (The Brain A-level notes)

The human brain:

• Brain is part of the CNS-information processed and coordinated response results.
• Spinal chord (CNS) contains grey matter; made up of neurone cell bodies, and white matter; made up of nerve fibres. 
• Brain has 3 distinct areas: forebrain (olfactory lobes+cerebral hemispheres), midbrain (optic lobes) and hindbrain (cerebellum+medulla).
• In vertebrate embryos: anterior end of tube swells and folds back on itself forming a brain. 
• Cerebral cortex folded back over the entire brain. 
• Human brain contains around one hundred thousand million neurones, each synaspsed to 10,000 other neurones-complex. 

Cerebral hemispheres: 

• Higher functions of brain; learning, feeling emotions, thought.
• Grey matter-nerve cell bodies, dendrites and synapses. 
• Deeply folded to give larger surface area. 
• Corpus callosum: band of axons (white matter) connecting hemispheres. 
• Frontal lobe: emotion, reasoning, personality. Idea+association development. Contains primary motor cortex involved in control of body movements via motor neurones in spinal chord. 
• Temporal lobe: auditory information, memory. 
• Occipital lobe: visual information (input from optic nerves). 
• Parietal lobe: varied functions; recognition, calculation, movement, sensation, spatial orientation. 

Other areas of the brain:

• Hypothalamus: coordinates autonomic nervous system, thermoregulation, monitors chemistry of blood (hormones from pituitary glands) and basic feelings; hunger, aggression, reproduction. 
• Cerebellum: coordinates smooth muscle movements, uses info from muscles+ears for balance.
• Medulla oblongata: primitive, contains reflex centres controlling heart rate, peristalsis etc. Maintains basic life responses even if higher areas destroyed. 

Animal studies:

• Removing/damaging areas of the brain (cerebral hemispheres) of an animal to observe effect on behaviour. 
• Implanting electrodes and artificially stimulating areas of the brain to see behaviour change.
• Normal behaviour compared with post mortem changes to brain. 
• Anthropomorphism is a problem.

Reptiles and facultative parthenogenesis

If you understand the title of this post, you have my undying respect. Most people wrongly assume  that asexual reproduction only occurs in prokaryotes and plants, by binary fission or runners for example, however animals can also reproduce in this manner, and not via divine impregnation. Seriously, if you are a devout catholic I suggest you leave this page and maybe read the Bible instead. In parthenogenesis an embryo develops from an unfertilised egg and the process occurs perfectly naturally in invertebrates like scorpions, and also in a select few vertebrates, like the Komodo Dragon (yes, it deserves capital letters). A normal egg cell produced by meiosis has the haploid number of chromosomes, as the other half of the offspring's genome is made up by the father's haploid sperm cell. However in parthenogenesis such haploid individuals are non-viable (may die during embryonic development or have a low zygote hybrid vigour) , and the parthenogenic offspring must often be diploid. Therefore full clones produced by parthenogenesis develop without the need for meiosis to manufacture haploid gametes in parents. But how is an embryo produced without without fertilisation? I hear you scream. Well, a mature egg cell is produced from mitotic oogenesis, which then develops directly into an embryo. This process is known as apomitic parthenogenesis, and is the less complex branch of the phenomenon. When parthenogenesis does occur with meiosis, offspring may be haploid, like the male ant, however there is often a complicated chain of processes which occur to restore diploidy to the offspring, in order to make them viable. However these offspring are only half clones of the parent organism, so they are genetically in-identical. But what I really want to talk about are the facultatively parthenogenic Komodo Dragons, which usually reproduce sexually, but can occasionally reproduce asexually. Therefore, when no viable males are present in a habitat, a female can ensure the survival of the species via parthenogenesis, making them more resistant to extinction than most species. What I particularly like about the Komodo Dragon, apart from its totally awesome name, is its ZW-sex determination, in which ZZ genotypes create males, ZW creates females, and in rare cases the WW genotype creates a female, however it is mostly unviable. Komodo Dragons are just too awesome for the XY sex determination system, although that may be a rather subjective analysis. In conclusion, the fact that an intelligent organism can clone itself in a pinch, to ensure the continued evolution of its species, is an incredible feat of mother nature. Imagine if we could induce parthenogenesis in humans? I mean, we've done it in fish...Actually, I don't like what I'm imagining. Bye!

Is this the Matrix?

Have you ever had a sudden panicked moment when you believe you've experienced something before? A conversation, a person or anything really. I know I certainly have, but thanks to science, I'm pretty sure that we are not all living in a computer generated world whilst robots harvest our body heat for energy. Deja Vu is not a glitch in the Matrix. The simplest, memory based, definition of Deja Vu is that a stimulus that triggers the feeling is linked to a similar memory that is already stored within the hippocampus, but which the person cannot remember. So if an event in the present has strong associations to a forgotten event in the past, then the feeling of Deja Vu is triggered. In 1941 researchers attempted to recreate the feeling in a laboratory, using hypnosis to induce post-hypnotic amnesia on volunteers. They were then shown a stimulus they had encountered before the hypnosis, yet only 3/10 people experienced Deja Vu. Spooky right? Although this test is of limited reliability given it's small sample size... so I wouldn't trust it implicitly. Recent virtual reality studies indicate that Deja Vu is more often triggered by the degree of familiarity felt in a certain situation, and so when a similar, familiar situation is encountered again, a person believes they have already lived through it. Location also appears to be important in this effect, as the degree of similarity between the spatial layouts of the previously experienced scene (which the person has forgotten) and the present scene increased the instance of Deja Vu in the VR test subjects. Cryptomnesia is another possible explanation for the phenomenon. I would like to take this moment to apologise to my readers who look down in haughty derision at the social sciences. Whilst I often do that myself, I thought this was too interesting a concept to pass up. Anyway brace yourselves, more unsupported conjecture coming your way. Cryptomnesia is essentially when information learnt is 'forgotten', but is still stored somewhere in the depths of the hippocampus, and is vaguely recalled based on more established concepts. The original memory is therefore distorted, and parts are omitted entirely. When this 'butchered' memory matches a current situation, Deja Vu is triggered. Each time we recall that 'memory' we are recalling our last construction of it. Deja Vu could therefore be a means of reconstructing and repurposing forgotten information to suit current needs. Although that theory does sound rather frivolous given its lack of scientific grounding. In truth, we don't fully understand the human brain, and researchers aren't really sure why Deja Vu like events are so different from person to person. Personally I think social conditioning has a part to play, as the populous are so aware of the phenomenon that they assume every half formed memory is Deja Vu. But then again, who doesn't want a little supernatural in their life?

Hibernate or hibernot

If the Land Rover advertising campaign is to be believed, us humans should not hibernate, as it is a waste of time during the cold winter months. Although, after reading new research published on the virtues of hibernation for neurodegenerative disorders, I believe this is an ill advised message. Who hasn't considered the concept of hibernation for humans? Just me? Ok, at first glance it doesn't seem a particularly attractive concept, going into a self induced 'coma-like' state during periods of low temperature, in a state of metabolic depression. Interestingly a process called  heterothermy occurs in hibernating mammals, during which they transition from being homeostatic endothermic to being ectothermic organisms, relying on their environment to regulate body heat, allowing for the slowing down of metabolic processes. The more you know right? But let's get back to the crux of this post: does hibernation actually have health benefits? Oh I'm so glad you asked. A UK team from the MRC Toxicology unit in Leicester have discovered the so called 'cold-shock chemicals' that cause mammals to destroy connections in their brains as they enter hibernation. Around 30% of synapses in the brain are destroyed, due to the slower metabolic rate during the winter. But what's truly amazing is that these culled synapses are reformed when the animal awakens in the spring! This obviously has huge implications for the medical profession, because the chemical released in the neural tissue as the animal begins to wake up and needs to repair synapses, RBM3, could be used to treat previously incurable conditions caused by prions, like Creutzfeldt–Jakob disease in humans. By artificially boosting levels of RBM3 in the brain, researchers have found that neurone death due to the misfolding of proteins caused by prions can be significantly reduced, and so we are one step closer to a drug that specifically targets the deadly neurone destroying agents that are prions. Memories are even retained after hibernation, as only the impulse receiving end of the synapses are destroyed (this is pretty obvious if you think about it, as a survival mechanism that wipes the animal's memory clean would be quite detrimental to its survival chances), and there is therefore a strong chance the RBM3 could be tailored into a drug to treat Alzheimer's patients, to slow down or even stop neurone loss during the early stages of the disease. Unfortunately the human body is not adapted to hibernate, as we don't produce enough RBM3 naturally, but I would certainly hibernate if given the chance. You would miss the most depressing months of the year, and reduce the risk of neurodegenerative disorders in later life. Stuff that in your gas-guzzling V8s Land Rover.

The MHCs: the immunological proteins you probably haven't heard of.

When one thinks of immunological proteins, you think of the big players; histamines, cytokines, and B/T cell receptors like CD4. However there are a little known family of proteins, that do play a vital role in the immune response, more specifically in antigen presentation, which make a bold claim in their name; the Major Histocompatability Complexes. In antigen presentation, a phagocyte like a macrophage or dendritic cell displays the antigens, which are specific peptide sequences used by the immune system to identify a pathogen, from the microbe it has just hydrolysed on its cell membrane. The protein the phagocytes use to do this is the MHC II. The phagocyte presenting these antigens will then travel to a lymphoid organ, the thymus or yellow bone marrow for example, through lymph and activate naive T cells. The CD4 receptor on the T cells must be able to dock to the MHC class II protein, so the epitope; the antigenic determinant which is recognised by the immune system, can imprint on the T cell receptor, priming it and therefore forming the effector T cells: the cytokine releasing T helpers which serve to rally the immune response, or the cytotoxic T killers which kill virally infected cells like homicidal spear wielding warriors. This in fact leads me on to the other class of Major Histocompatability Complex: MHC I. I made a passing reference to it as a 'surface marker' used in the immune response during a previous post, most people would stop there and move on to more significant proteins like interferon, but I'm not like most people (hence this blog). MHC I can be expressed on the surface membrane of almost every body cell, and it also displays the epitopes of antigens when, but for an altogether more sinister purpose... Ok that was slightly dramatic, but I doubt most people will read this far into the entry, so I can do what I want down here (whilst still remaining factually correct of course). The cells displaying epitopes on MHC I are virally infected, and can dock with the CD8 glycoprotein and the TCR found on the surface of T killer cells, and so they release cytotoxins like perforin, which destroys the cell membrane thus promoting PCD by apoptosis. How neat. So without this often overlooked protein, there would be no antigen presentation to trigger the adaptive Immune system, or pleasingly efficient destruction of virally infected cells. It just goes to show how interdependent every molecule in our bodies are, a principle that one should both admire and be absolutely petrified about...

Toxoplasma gondii: the parasite with a penchant for felids

If you hadn't already realised, dear readers, I'm a huge nerd. Wipe that look of shock off your faces. Anyway, I've been extremely busy with Pokemon Alpha Sapphire, revision and Fullmetal Alchemist. I'm only human ok! I've also been working tirelessly on my Extended Project, a 5,000 word dissertation of the topic of feline intelligence. Most people chose sensible topics like stem cell research, the UK's involvement in the EU, or the parallels between historical leaders, but I, in an attempt to make my life that little bit more difficult, decided to pick a topic that has very little debate, and even fewer people who are interested in the answer. Whilst I was researching the controversial topic of the intelligence of the domestic cat, I stumbled upon a parasite known as Toxoplasma gondii (T. gondii), as T. gondii's primary host is the domestic cat. T. gondii is a unicellular eukaryotic organism, a protozoan, that causes a disease called Toxoplasmosis in human host cells. Toxoplasmosis is the root of the term 'crazy cat lady' syndrome, as there is a definite link between the disease and mental health issues like schizophrenia, although most hosts are just symptomless carriers. Great. That's what I've got to look forward to.  It is one of the most common parasites found in the human body, and it is estimated that 1/3 of the global population is infected. The parasite can reproduce asexually within virtually all exothermic mammals, however it can only reproduce sexually in the intestines of Felids. This basically means it can only adapt and change its structure to evade our immune systems within cats, making them its definitive host. In order to optimise its chances of infecting cats, T. gondii can alter the behaviour of intermediate hosts like mice, to make them attracted to the scent of cat urine, so they are more likely to be preyed on by a passing feline. To do this the parasite hijacks white blood cells, which seem to be the target for pathogenic attack quite frequently (even parasites have a sense of humour). The WBCs are converted into chemical factories, synthesising neurotransmitters like serotonin, to reduce response of fear and anxiety that usually occurs in the amygdala of the mouse, as soon as it smells a feline nearby. The parasite resides within a membrane known as an oocyst until it passes through the stomach and the membrane is hydrolysed. It then infects epithelial cells, in which it is converted to Tachyzoite cells, speeding up the rate of proliferation, then they are converted to slow dividing Bradyzoites, which form tissue cysts in the host, completing the parasite's lifecycle. It's a feat of biological adaptation that a parasite can become so ultra-specialised to one particular host, but like a lot of evolution and natural selection, this mechanism is kept because it works. It worked during the evolution of the parasite, and so that's what it does to this day, and what it will continue to do until domestic cats develop a resistance to it. T. gondii stubbornly resists change, and that's why I like it...

Vitamin D: the mechanism, the molecule, the screenplay

What's hip loyal biologists? (obviously not this blog) Today on my quest for knowledge of our biological universe, I came across the fascinating, fat soluble steroid known as Vitamin D. The D2 and D3 molecules to be more precise. You've probably heard of rickets, and a bit about how the sun stimulates Vitamin D's release in our bodies. If you're an introvert obsessed with science and video games like me, then you know where I'm coming from. Vitamin D is vital in our bodies to enhance absorption of key minerals in the intestinal system, like calcium, iron or zinc. These elements are used to construct and maintain our skeletal system, so that's why if children develop a vitamin D deficiency, their bones can become elongated and deformed, because they cannot absorb enough calcium or phosphorous for proper skeletal development. Although this mostly occurs in countries with a high prevalence of genetic disorders such as pseudovitamin D deficiency rickets. Vitamin D is marketed on the internet as a miracle cure for conditions like cancer, heart disease, depression and autoimmune disease, despite the fact that no clinical trials have proven this claim. In fact they mostly say Vitamin D has a negligible impact on such conditions. The D3 vitamin molecule is produced in the skin, when exposed to UV light, from another molecule called 7-dehydrocholesterol. This precursor of vitamin D3 is produced in relatively large quantities, in fact 10,000 to 20,000 IU of vitamin D are produced in 30 minutes of whole-body exposure, in the skin of most vertebrate animals. 7-dehydrocholesterol is converted into D3 by UVB rays between 270 and 300 nm, but occasionally an equilibrium can form in the skin, in which vitamin D degrades as fast as it is synthesised. But that's not the end of vitamin D's journey in the body. In the liver it is converted into a prohormone (precursor to a hormone) known as calcidiol, and then it is converted yet again in the kidneys, but this time to its biologically active form; calcitriol (a bit like phytochromes in plants for you botanists out there) . Calcitriol binds to the vitamin D-binding protein, which transports it to vitamin D-rerceptors (VDRs) on the surface of target cells. Here's where it gets really good. The VDRs bound to vitamin D will act as transcription factors, promoting expression of transport proteins like TRPV6 (catchy right?) within cells,  which are involved in absorption of calcium in the immune system. So what have we learnt? For one thing the proteins and receptors involved with Vitamin D have incredibly uncreative names. But on a more serious note, sunlight is essential to skeletal health, so maybe we should embark on adventures is the great outdoors more frequently! I'm such a hypocrite... 

Avian flu: taking flight?

On 16th November a duck breeding farm in Yorkshire tested positive for avian flu, so as you can imagine DEFRA was on the scene immediately, introducing a 10km restriction zone and culling all 6,000 birds on the farm to prevent further spread of the disease. But why? Is avian flu so contagious, that such an extreme response was warranted? Is it that dangerous? Let's find out shall we. Avian flu is caused by the influenza A strain of the influenza virus (although A does not stand for avian). All subtypes of influenza A are adapted to be able to use birds as a host, but are not always zoonotic (can pass from animals to humans). Influenza A is what is known as an  single stranded antisense RNA virus, meaning its single strand of RNA (3'-5') runs complementary to viral mRNA (5'-3')  that it encodes. This means it must carry RNA polymerase within the virion particle, as the viral RNA cannot be directly translated into protein, it  must be transcribed first, rather like DNA. Influenza A can be categorised into 2 subtypes based on the protein used to construct its membrane: Hemagglutinin (H) or Neuraminidase (N) . The H protein causes agglutination of red blood cells in the host, and mediates the binding of a virion particle to the host cell and entry of the viral genome into the host cell genome.  Whereas N is an enzyme that breaks the glycosidic bonds in the monosaccharide, neuraminic acid, commonly found in animal cells as glycoprotein and it also controls the release of new virion particles from host cells. Different strains of influenza virus encode for different types of N and H which all play a specific role in the viral lifecycle, for example H5N1 virus  contains type 5 Hemagglutinin and type 1 Neuraminidase (oh how I love arbitrary numbers used to name pathogens). Interestingly, these 2 proteins form the antigens that allow antibodies produced by B cells to bind to the microbe, so macrophages can phagocytose it. Ok,  I think I've indulged you enough in the virus' structure and nomenclature, so let's talk about the birds. The outbreak in Yorkshire recently was H5N8 strain, which is of very little threat to people. In fact no one has died from it. Ever. The avian flu strains that you really have to worry about are H7N9 continually reported in poultry in China, and H5N1, which has a 60% case mortality rate across 15 countries (since 2003). Migratory fowl can act as asymptomatic carriers for the virus, which is probably how it reached the UK in the first place, and strains like H5N1 are not limited to birds and people; in New England 400 harbour seals were killed by the pathogen in a 1978 epidemic. Ok, so we know that certain strains of influenza A are deadly to people, but if the H5N8 strain poses no threat to us, why were all the ducks killed? Well, because of the high mutation rate of the virus, and its ability to hybridise with strains from other species, it could quickly become a human epidemic. So before we start arguing over the 'poor ducks' that were 'murdered', we must consider the potential threat of any strain of influenza to humans.

Immunology: your life depends on it

The mechanisms employed by the human body to destroy and to resist pathogen infection are simply breathtaking. The field of immunology is vast, and often taken for granted by the less inquisitive of our race, so my aim for this post is to dispel any doubt about how vital our immune system is, and perhaps put the fear of the fictional god in your heart. Let's start with the basics: most mammalian immune systems are split into 2 tiers: the innate and adaptive immune systems. The innate response is usually triggered by pathogens being detected by pattern recognition receptors, which respond to generic microorganism components or the cries for help from body cells. The innate immune system is therefore non-specific, so it does not produce antibodies, but it can act on a wide range of microbes, making it the first and main line of defence against disease in the human body. There are multiple components to this immune system; surface barriers like our skin and mucus,  mechanical barriers like coughing up mucus filled with pathogens to protect the lungs and respiratory tract and biological barriers, like the gut flora in our intestines which competes against parasitic pathogens. Inflammation in response to injury is also part of the innate system; compromised cells release signalling molecules (like cytokines) to dilate blood vessels and attract white bloods cells (leukocytes), specifically phagocytes, which digest the invading pathogens. The mammalian complement system is is another vital part of this response. Essentially, complement proteins bind to carbohydrate receptors on the surface of microbes, triggering a cascade of protease-like molecules which break down the surface of a microbe, rendering it inactive. It's a bit like the body's version of a gatling gun. The final elements of the innate system are the natural killer cells, which detect cells with low levels of a surface marker called MHC, meaning the cells are infected or cancerous, and they are destroyed. NK cells aren't concerned about trivial things like collateral damage... 
Let's now move on to the adaptive immune system, which is definitely my favourite, if you can have a favourite layer of the immune system. It is more potent, and is capable of remembering microbes because of their signature antigens, to speed up immune response. Therefore the adaptive immune system is antigen specific, so can recognise specific antigens in antigen presentation of cells. This system employs more variants of leukocytes, known as lymphocyte B cells and T cells. The B cells produce antibodies to target specific antigens on microbes, causing them to bind together, making it easier for phagocytosis to occur. The T kills can split into 2 kinds: T helper cells and T killer cells. T killer cells kill cells infected with pathogens (viruses in particular), and each one recognises a specific antigen (like everything in this system). When activated T killer cells release cytotoxins into compromised cells, inducing apoptosis. How neat. T helper cells regulate the immune response, by directing other cells to perform immunological tasks like digesting pathogens or producing antibodies. The most impressive thing about B and T cells is that their daughter cells can become long-lived memory cells, which remember specific antigens encountered in the past, and so can produce a particularly powerful immune response if that antigen is detected in the body again. Just from this brief overview of the immune system (trust me, this is heavily summarised), I hope you can see how vital every mechanism is to our health. Your heart may keep blood flowing around your body, your lungs may be the centre of gas exchange, but they would be meaningless without the protection the immune system affords your body. Next post I'll be describing what happens when the immune system fails. Trust me, it will be terrifying. 

Retrotransposons: bringing disco back?

Sorry about the cliffhanger in the last post. I lied, I'm moving on to a new topic today: the humble retrotransposon, although its hardly humble considering 48% of our genome is made up of transposons or their remnants. A retrotransposon is a piece of DNA that doesn't code for a protein (no DNA codes directly for proteins, but you know what I mean), but it codes for an abnormal piece of RNA. It can roam the genome freely, unlike most other RNA molecules. They can replicate infinitely using this RNA intermediate, and thus increase the frequency of certain elements of the genome. But how exactly do they do this as RNA? Well, it does this by breaking the rules. The biological dogma states that DNA codes for RNA, which codes for proteins, and they code for nothing. However the retrotransposon can use an enzyme known as reverse transcriptase, which it codes for, to become deoxyribonucleic acid again. Retroviruses can also do this with their genetic material (hence the 'retro' in their names). Retrotransposons can induce mutations, and cause malfunction in gene regulating mechanisms by inserting themselves between, or even directly into genes, which makes them useful for studying epigenetic mechanisms like DNA methylation. In mice for example the variation in expression of a retrotransposon due to methylation affects expression of the agouti coat colour gene, as usually RNA from retrotransposons messes up control of downstream agouti gene keeping it switched on continuously, leading to coat colour variability between genetically identical individuals, purely due to molecular modifications to the DNA. Furthermore, the mutations introduced by retrotransposons are very stable, because the base sequence at the insertion site stays constant as they transpose via semi-conservative DNA replication. As retrotransposons age they often accumulate mutations, and so are unable to retrostranspose. Transposition and survival of retrotransposons within the host genome are regulated both by retrotransposon- and host-encoded factors, to avoid deletion of elements of the retrotransposon and the host genome, in a symbiotic relationship that has existed for millions of years between retrotransposons and their hosts. The study of how retrotransposons and their host genomes have co-evolved mechanisms to regulate; transposition, specific insertion sites, and mutational outcomes to optimise each other's survival is still a developing field, which I find quite amazing, considering that the retrotransposons represent about 50% of our genome. We don't even know if most of them do anything, they're almost like outsiders in our own bodies...