Tag Archives: biology

A matter of inheritance

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Image courtesy of 'Digital Dreams' / FreeDigitalPhotos.net

Image courtesy of ‘Digital Dreams’ / FreeDigitalPhotos.net

The age-old ‘nature-nurture’ debate revolves around understanding to what extent various traits within a population are determined by biological or environmental factors. In this context ‘traits’ can include not only aspects of personality, but also physical differences (e.g. eye colour) and differences in the vulnerability to disease. Investigating the nature-nurture question is important because it can help us appreciate the extent to which biological and social interventions can affect things like disease vulnerabilities, and other traits that significantly affect life outcomes (e.g. intelligence). The ‘nurture’ part of this topic can be dealt with to some extent by research in disciplines such as Sociology and Psychology. In contrast genetic research is crucial to understanding the ‘nature’ part of the equation. Genetics also has relevance for the ‘nurture’ part of the debate because environmental factors such as stress and nutrition affect how genes perform their function (gene expression). Indeed genetic and environmental factors can interact in more complex ways; certain genetic traits can alter the probability of an organism experiencing certain environmental factors. For example a genetic trait towards a ‘sweet tooth’ is likely to increase the chances of the organism experiencing a high-sugar diet!

Given the importance of genetic information to understanding how organisms differ, I would argue that a basic knowledge of Genetics is essential for anyone interested in ‘life sciences’. This is true whether your interest is largely medical, psychological or social.  Unfortunately if, like me, you skipped A-Level Biology for something more exciting (or A-Level Physics in my case!) you might Genetics at bit of mystery.

Some basic genetics

Genetic information is encoded in DNA (Deoxyribonucleic acid). Sections of DNA that perform specific, separable functions are called Genes. Genes are the units of genetic information that can be inherited from generation to generation. Most Genes are arranged on long stretches of DNA called chromosomes, although a small proportion of genes are transmitted via cell mitochondria instead. Most organisms inherit 2 sets of chromosomes, one from each parent. Different genes perform different functions, mostly involving the creation of particular chemicals, often proteins, which influence how the organism develops.  All cells in the body contain the DNA for all genes, however only a subset of genes will be ‘expressed’ (i.e. perform their function) in each cell. This variation in gene expression between cells allows the fixed (albeit very large) number of genes to generate a vast number of different chemicals. This in turn allows organisms to vary widely in form while still sharing very similar genetic information (thus explaining how it can be that we share 98% of our DNA with monkeys, and 50% with bananas!).

The complete set of genetic information an individual has is called their ‘genotype’. The genotype varies between all individuals (apart from identical twins) and thus defines the biological differences between us. In contrast the ‘phenotype’ is the complete set of observable properties that can be assigned to an organism. Genetics tries to understand the relationship between the genotype and a particular individual phenotype (trait). For example how does the genetic information contained in our DNA (genotype) influence our eye colour (phenotype)? As already mentioned environmental factors play a significant role in altering the phenotype produced by a particular genotype. Explicitly the phenotype is the result of the expression of the genotype in a particular environment.

Heritability

Roughly speaking, heritability is the influence that a person’s genetic inheritance has on their phenotype. More officially it is the proportion of the total variance in a trait within a population that can be attributable to genetic effects. It tells you how much of the variation between individuals can be attributed to genetic differences. Note that this is not the same as saying that 60% of an individual’s trait is determined by genetic information. In narrow-sense heritability (the most common form used), what counts as ‘genetic effects’ is only that which is directly determined from the genetic information past on by the parents. This ignores variations caused by the interaction between different genes, and between genes and the environment. This is the most popular usage of heritability in science because it is far more predictive of breeding outcomes, and therefore tells us more about nature part of the ‘nature-nurture’ question, than the alternative (broad-sense) conceptualisation of heritability.

Uses and abuses

Genetic research can provide crucial information in the fight against certain diseases. Identifying genes that are predictive of various illnesses allow us to identify individuals who are vulnerable to a disease. This then allows preventive measures to be implemented to counter the possible appearance of the disease. Furthermore once the genes that contribute to a disease are known, knowledge as to how those genes express will help reveal the cellular mechanisms behind the disease. This improves our understanding of how the disease progresses and operates, and therefore helps with identifying treatment opportunities. In reality of course Genetics is rarely this simple. Many conditions that have a genetic basis (i.e. that show a significant level of heritability) appear to be influenced by mutations within a large number of different genes. Indeed in many cases, especially with psychiatric disorders, it may be that conditions we treat as one unitary disorder are in fact a multitude of different genetic disorders that have very similar phenotypes. Nevertheless, despite these problems genetic research is helping to uncover the biological basis of many illnesses.

One problem with Genetics, and heritability in particular, is that of interpretation. There is often a mistaken belief that a high level of heritability signifies that environmental factors have little or no effect on a trait. This misunderstanding springs from an ignorance of the fact that estimates of heritability comes from within a particular population, in a particular environment. If you change the environment (or indeed the population) then the heritability level will change. This is because gene expression is affected by environmental factors and so the influence of genetic information on a trait will always be dependent to some extent on the environment. As an example a recent study showing that intelligence was highly heritable (1) lead to some right-wing commentators using it as ‘proof’ of the intellectual inferiority of certain populations, because of their lower scores on IQ tests. Such an interpretation is then used to argue that policies relating to equal treatment of people are flawed, because some people are ‘naturally’ better. Apart from the debatable logic of the argument itself, the actual interpretation of the genetic finding is flawed because a high heritability of IQ does not suggest that environmental differences have no effect on IQ scores. To illustrate this point consider that the study in question estimated heritability in an exclusive Caucasian sample from countries with universal access to education. If you expanded the sample to include those who did not have access to education it would most likely reduce the estimate of heritability, as you would have increased the influence of environmental factors within the population being studied! Ironically therefore you could argue that only by treating everyone equally would you be able to determine those who are truly stronger on a particular trait! Independent of what your views on equality are, the most important lesson as regards genetics is that you cannot use estimates of heritability, however high, to suggest that differences in the environment have no effect on trait outcomes.

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 References

(1) Davies, G. et al (2011) Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Molecular Psychiatry 16, 996-1005. http://www.nature.com/mp/journal/v16/n10/full/mp201185a.html

Although not directly cited, I found the following information useful when creating the post (and when trying to get my head around Genetics!).

Quantitative Genetics: measuring heritability. In Genetics and Human Behaviour: the ethical context. Nuffield Council on Bioethics. 2002.  http://www.nuffieldbioethics.org/sites/default/files/files/Genetics%20and%20behaviour%20Chapter%204%20-%20Quantitative%20genetics.pdf

Visscher, P.M., Hill, W.G. & Wray, N.R. (2008) Heritability in the genomics era – concepts and misconceptions. Nature Reviews Genetics, 9 255-266. http://www.ncbi.nlm.nih.gov/pubmed/18319743

Bargmann, C.I. & Gilliam, T.C. (2012) Genes & Behaviour (Kandel, E.R. et al (Eds)). In Principles of Neural Science (Fifth Edition). McGraw-Hill.

Neuroscientists Make Declaration On Animal Consciousness

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Scientists have officially acknowledged that birds have consciousness, and can experience emotions.

On 7/7/2012 a group of prominent neuroscientists signed a declaration supporting the view that non-human animals experience consciousness. The statement claims to be a ‘re-evaluation of previously held preconceptions’. It states that:

‘Convergent evidence indicates that non-human animals have the neuroanatomical, neurochemical and neurophysiologial substrates of conscious states, along with the capacity to exhibit intentional behaviours‘.

Unfortunately the declaration doesn’t define clearly what exactly the ‘consciousness’ they are referring to is. Instead the text switches between referring to different elements of conscious experience, such as arousal (e.g. levels of sleep and attentiveness), conscious decision making, perceptual distortions (e.g. hallucinations) and the experience of emotional states. As the concept of consciousness is a notoriously difficult one to define, the lack of an operational definition makes the declaration somewhat difficult to interpret.

A further peculiarity of the declaration is that it states something which I suspect the vast majority of scientists working in the fields of neuroscience, psychology and animal behaviour have believed for some time. Indeed I suspect a significant proportion of the ‘general public’ would accept that most animals have some level of conscious understanding, especially mammals. The declaration isn’t therefore heralding a breakthrough in scientific understanding, even if it does contradict certain religious and philosophical standpoints that propose consciousness as a uniquely human characteristic.

Despite these reservations, the declaration may prove to be of importance. It focuses on the commonalities between different animals in the neural structures supporting various conscious experiences, and discusses the implications this may have for understanding the development of consciousness through evolution. It represents an official acknowledgement that a larger range of animals experience consciousness that many may have previously believed, based off the proposition that absence of a cerebral cortex does not preclude conscious thought. Those animals considered ‘conscious’ can therefore include non-mammalian creatures such as insects and cephalopods. The declaration may hopefully lead to greater discussion of both the nature of consciousness, and the relationship between humans and other animals.  More importantly it may facilitate political changes to ensure the more humane treatment of animals.

A full text of the declaration can be found at http://fcmconference.org/img/CambridgeDeclarationOnConsciousness.pdf

Scientists discover bees that can reverse brain aging

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By Maria Panagiotidi

Scientists at Arizona State University have discovered that older honey bees can reverse brain aging when they take on nest responsibilities typically handled by much younger bees.

This finding could provide alternative interventions for the treatment of age-related dementia. Current research focuses mainly on potential new drug treatments.

The study was published in the scientific journal Experimental Gerontology by a team of scientists from ASU and the Norwegian University of Life Sciences, led by Gro Amdam. The researchers found that tricking older, foraging bees into doing social tasks inside the nest causes changes in the molecular structure of their brains.

Previous research on honey bees has found that bees that stay in the nest and take care of larvae – the baby bees – remain mentally competent. However, after a period of nursing, bees fly out looking for food and begin aging very quickly. The effects of aging are visible after two weeks in the appearance of the foraging bees (worn wings, hairless bodies) and more importantly, in their brain function. Specifically, these bees lose the ability to learn new things.

Influenced by recent studies on brain plasticity, Amdam and colleagues wanted to see what would happen if the foraging bees returned to the nest and took care of the larval babies again.

The results of the experiment were fascinating. After 10 days, about 50 percent of the older bees caring for the nest and larvae had significantly improved their ability to learn new things.

The change observed in the older bees was not just behavioural but also physiological; Amdam and colleagues discovered a change in proteins in the bees’ brains. After comparing the brains of the bees that improved to those that did not, they found that two proteins had noticeably changed: Prx6 and “chaperone” protein. Both proteins have been previously found to protect the brain against diseases such as Alzheimer’s.

This finding could lead to the development of a drug that could help older people maintain brain function. However, many years of basic research and trials will be needed before such a drug becomes commercially available.

For now, Amdam and colleagues propose that social interventions might help our brains stay younger. Since the proteins being researched in people are the same as those found in bees, it is possible that these proteins may be able to respond to specific social experiences. Further research is needed on mammals in order to confirm that the same molecular changes occur on other species’ brains.

 

Reference

Nicholas Baker, Florian Wolschin, Gro V. Amdam. Age-related learning deficits can be reversible in honeybees Apis mellifera. Experimental Gerontology, 2012; DOI: 10.1016/j.exger.2012.05.011

First Steps Toward Emergence of Life Theory

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By Stephen Sadler

What turned a primordial mixture of amino acids and proteins into the first organized, self-replicating unit? What was it that breathed the vital breath into a collection of inanimate chemical building blocks, giving rise to an unbroken chain of evolution stretching three and a half billion years into the future and culminating in us?

For many years Kauffman has studied the mathematics behind groups of molecules known as ‘autocatalytic sets’. These sets of molecules and their associated chemical reactions are special because they form self-sustaining systems which, given a ‘food source’ of simple molecules, are able to form more complex molecules which themselves catalyse, or speed up, reactions which give rise to other molecules in the set. In this way, they form “functionally closed” structures (see Figure 1) that speed up the production of the members of the set, promoting the existence of the set as a whole.

Figure 1: an example of an autocatalytic set. Black dots represent molecules in the set, whilst white boxes represent reactions. Solid arrows stand for reaction inputs and outputs, and dashed arrows indicate catalysis. Because each arrow ends on a molecule in the group, the group is said to be “functionally closed”.

To see what all this has to do with life, we must define what we mean by “life”. Whilst definitions vary, most share some common themes, for example: self-organisation, self-replication, and the ability to evolve with successive generations. Kauffman himself has defined a living organism as “an autonomous agent or a multi-agent system capable of reproducing itself or themselves, and of completing at least one thermodynamic work cycle” [1].

So could autocatalytic sets fulfil these criteria? Almost by definition their existence promotes the proliferation of their constituents, which sounds remarkably like self-replication. Their closed structure and well-defined flow of reactants and catalysts through reactions also sounds like it might fulfil the self-organisation criterion. But can they evolve? It is this question that Kauffman’s latest work addresses.

The group studied the mathematical properties of autocatalytic sets and made the remarkable discovery that any given set can be decomposed into so-called ‘irreducible autocatalytic sets’. What’s more, the number of irreducible autocatalytic sets that any larger autocatalytic set can be decomposed into rises exponentially with the size of the larger set. Since these sets overlap to some degree, they can be said to be mutually dependent, and it is not too much of a leap of faith to imagine them beginning to behave as the elements of a ‘meta autocatalytic set’.

“In other words, self-sustaining, functionally closed structures can arise at a higher level (an autocatalytic set of autocatalytic sets), i.e., true emergence,” the group say.

The combining and splitting of these functionally-closed, self-replicating entities can, according to the group’s paper, give rise to inheritance, mutation and competition. In other words: evolvability.

However, the authors don’t stop there. Is it too far fetched, they ask, to “consider a complete cell as an (emergent) autocatalytic set?” And if not, then why not think “of the collection of bacterial species in your gut (several hundreds of them) as one big autocatalytic set”? Going one step further, could the theory not be applied to ecology to describe any mutually dependent set of organisms, they ask? Could the economy not be viewed as an autocatalytic set, with its processes (reactions) assembling complex structures out of more simple ones (reactants), facilitated by tools, factory production lines and humans (catalysts)?

These are big ideas and, by the authors’ own admission, rather speculative, but with the tantalising possibility of a single theory to explain the phenomena of emergence, functional organisation and the origin of life, it seems difficult to disagree with them when they conclude: “we believe that these ideas are worth pursuing and developing further”.

A preprint version of the group’s paper can be found at http://arxiv.org/abs/1205.0584

[1] 2004, “Autonomous Agents”, in John D. Barrow, P.C.W. Davies, and C.L. Harper Jr., eds., Science and Ultimate Reality: Quantum Theory, Cosmology, and Complexity, Cambridge University Press.

 

Scientists Implant Biofuel Cell in Living Snail

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By Maria Panagiotidi

Researchers led by Evgeny Katz, the Milton Kerker Chaired Professor of Colloid Science at Clarkson University, have implanted a biofuel cell in a living snail. Their findings were published in the Journal of The American Chemical Society.

Researchers led by Evgeny Katz, the Milton Kerker Chaired Professor of Colloid Science at Clarkson University, have implanted a biofuel cell in a living snail. This is the first incidence of an implanted biofuel cell continuously operating in a snail and producing electrical power over a long period of time using the snail’s physiologically produced glucose as a fuel. (Credit: Image courtesy of Clarkson University)

The “implanted battery” can generate electrical power for several months driven by glucose, which is produced by the snail.

This is the first reported incident of an implanted biofuel cell operating in a snail and producing electrical power over a long period of time using as fuel the glucose that is physiologically generated by its host.

Implantable biofuel cells have been suggested as sustainable micropower sources operating in living organisms, but such systems are still very challenging to design. In the future, implanted fuel cells that are driven by glucose generated by their host could power medical devices in humans or environmental sensors in animals.

Evgeny Katz and his colleagues made the electrodes of their fuel cell out of densely packed carbon nanotubes, and attached glucose-oxidizing and oxygen-reducing enzymes to them. The authors then implanted the electrodes into a snail (Neohelix albolabris). After decreasing the rate of current extraction to match the snail’s slow glucose transport and metabolism, they got continuous electrical output for an hour. The amount of electricity produced was far below that of just one AAA battery, but the group of scientists aim to increase it in future experiments. The fuel cell remained functional in the snail for several months during which the animal was allowed to roam freely and live an almost normal life.

The aim of this research is creating insect cyborgs, an idea that has been funded by the U.S. Department of Defense.

 

Reference

Lenka Halámková, Jan Halámek, Vera Bocharova, Alon Szczupak, Lital Alfonta, Evgeny Katz. Implanted Biofuel Cell Operating in a Living Snail. Journal of the American Chemical Society, 2012; : 120308155036002 DOI:10.1021/ja211714w

You can find the article here:  http://pubs.acs.org/doi/abs/10.1021/ja211714w 

 

 

Turmeric could help ward off Parkinson’s disease

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By Holly Rogers

Curcumin, found in turmeric, has been shown to prevent protein clumping in the brain. This clumping has been recognised as an early stage of Parkinson’s disease.

Scientists at Michigan State University have used lasers to watch proteins being rescued by curcumin, building on research released earlier this year into the mechanism of clumping.

“Our research shows that curcumin can rescue proteins from aggregation, the first steps to many debilitating diseases,” said Lisa Lapidus, co-author of the study.

KurkuminaProteins are needed to carry out most of the work done by cells, and are built through a process known as folding. If the protein does not fold fast enough, it begins to clump and bind to other proteins around it. Curcumin not only stops this binding from happening, but speeds up the folding process, lowering the chances of it starting again. However, there is still more research to be done before curcumin becomes a routine treatment.

“Curcumin’s usefulness as an actual drug may be pretty limited since it doesn’t go into the brain easily,” said Professor Lapidus. “But this kind of study showcases the technique of measuring reconfiguration and opens the door for developing drug treatments.”

Curcumin is being currently investigated for possible benefits in various clinical conditions such as Alzheimer’s disease, and some types of cancer.

Reference:

B. Ahmad and L. J. Lapidus, Curcumin Prevents Aggregation in α-synuclein by Increasing the Reconfiguration Rate, Journal of Biological Chemistry, 2012.

You can find the original article here: http://www.jbc.org/content/287/12/9193.abstract

 

The Immune Cell, the Neutrophil – the Good, the Bad, or the Ugly?

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By Kathryn Higgins

Throughout our lifetime our bodies sustain infections and injuries, and the body deals with them by mediating an inflammatory response. This happens by cells within our blood entering the site of infection or injury and carrying out multiple biological reactions. These reactions can kill the microorganism that has caused the infection, but also heal at the site of injury, and hence resolve inflammation. These blood cells are collectively called white blood cells or leukocytes, and there is one in particular, named the neutrophil, which not only helps to resolve inflammation but can also exacerbate the condition further. This has resulted in the neutrophil having a reputation for being both ‘good’ and ‘bad’ in inflammatory conditions.

The reputation of the neutrophil is influenced by many molecules that are released from other cell types during inflammation. These molecules influence the activity of the neutrophil in various ways, either stimulating the cell so inflammation can be resolved or inhibiting a particular function the cell has. The influence of these molecules determines whether the neutrophil is able to carry out its functions efficiently or whether the inflammatory condition will be aggravated further. The biological activities of neutrophils therefore need to be understood to comprehend how they function and how these roles can be modulated to determine what effect this has during an inflammatory response.

Neutrophils form part of the body’s innate immunity which involves a series of defence mechanisms that protect the host from infection and form the early barriers to infectious diseases without relying on the production and expansion of antibodies that form the adaptive immune response. When an infection occurs, the innate immune response is triggered to rapidly detect and destroy the infection. Neutrophils are one of the first blood cells to respond to infection and are recruited from the circulating blood into the tissue by molecules called chemoattractants1. These molecules, released from cells at the site of infection and also from the microorganism, also known as a pathogen, provide a chemical gradient for neutrophils to migrate along, with the highest concentration of these chemoattractants situated at the site of infection, so the cells are led directly to the infected site. Once in the tissue the lifespan of the cell is increased to approximately 1-2 days as opposed to 6-10 hours in the circulation. This is to lengthen the amount of time neutrophils have to carry out their functions and resolve inflammation.

A vital part of the innate immune response is the ability of the neutrophils to engulf pathogens and aid the resolution of infection. This process is called phagocytosis and classifies the neutrophil as a phagocyte, so called after the Greek for ‘devouring cells’. When the neutrophil has entered the infected site and detected the pathogen, the outer membrane of the neutrophil surrounds the pathogen to engulf it and so the pathogen becomes taken up into the cell. Neutrophils contain many granules and these are packed with lots of toxic reagents. Upon engulfment these granules fuse with the pathogen and release their toxic contents, by a process called degranulation, and these contents assist in the killing of the pathogen2.

In addition to degranulation, neutrophils can also kill pathogens by oxidative mechanisms, so called because molecular oxygen is required. This involves a process named the respiratory burst and it is the major mechanism by which neutrophils kill and digest pathogens. During the engulfment of a pathogen into the neutrophil, molecular oxygen is also rapidly taken up. The oxygen is then converted, by a series of chemical reactions, into several toxic compounds such as hydrogen peroxide. Further chemical reactions may occur producing even more potent substances3 and when the pathogen becomes exposed to these various toxic oxygen metabolites the pathogen is digested and destroyed within the cell.

Neutrophils have also been shown to kill pathogens outside of the cell, i.e. extracellularly, rather than engulfing them. This occurs by neutrophils releasing web-like structures of genetic material, called neutrophil extracellular traps (NETs)4. These NETs are composed of fibres that trap pathogens, and have been proposed to contain high concentrations of anti-microbial compounds, such as those contained within their granules, to kill pathogens and prevent the spread of infection. Some bacteria, however, have evolved to counteract being killed by NETs by producing substances that degrade the genetic material that make up NETs, such as Streptococcus pneumoniae5, which is known to be the common cause of pneumonia.

Once the pathogens have been dealt with, and to completely resolve inflammation, neutrophils need to be cleared from the tissue. If the cells do not become removed then all their toxic contents, such as the granule contents and oxygen metabolites that kill pathogens, may leak out of the cell and damage surrounding cells and tissues, which will only make the inflammatory condition worse. For removal, neutrophils firstly need to die. This is by a programmed type of cell death termed apoptosis6 which ensures that the cellular membrane remains intact so these toxic contents are retained within the cell and cannot be released. During this cell death a fatty (lipid) molecule called phosphatidylserine is flipped to the outer surface7. This lipid acts as a signal for tissue macrophages to target the dead neutrophil. Tissue macrophages are another class of white blood cell with a vital role of recognising apoptotic cells. Once the signal has been recognised, the neutrophil itself is then engulfed by the macrophage and cleared from the tissue. It is essential that these apoptotic cells are removed efficiently from the tissue because a delay in their clearance can also increase the chance of their intact membranes becoming leaky.

Apoptosis is therefore a process which needs to be tightly regulated to ensure inflammation is resolved efficiently. If cell death is stimulated too early then the number of functional neutrophils in the tissue is reduced. This would limit the hosts’ ability to fight infection and resolve inflammation. For example, some infections induce neutrophil apoptosis, such as the influenza A virus8 and the Pseudomonas aeruginosa bacterium9 to favour their own survival. In contrast to this, if apoptosis is delayed, as seen with the inflammatory joint disorder rheumatoid arthritis10, the number of circulating cells in the tissue increases, toxic contents may then be released from the cells, and surrounding tissue would be damaged potentiating inflammation further. This contrasting effect of the neutrophil is often referred to as the ‘double-edged sword’ effect, i.e. can be both ‘good’ and ‘bad’ during the inflammatory process, with the damaging effects of the neutrophil quickly out-weighing the benefits. Although neutrophils may often appear to be the ‘bad’ guy in certain inflammatory conditions this is typically due to the influence of other molecules released from surrounding cells. Without this influence the primary aim of the neutrophil is to resolve inflammation, making them overall the ‘good’ guys of the inflammatory process.

References:

  1. Yoshimura, T., Matsushima, K., Tanaka, S., Robinson, E.A., Appella, E., Oppenheim, J.J. and Leonard, E.J. (1987) Proc. Natl. Acad. Sci. USA 84, 9233-9237
  2. Campanelli, D., Detmers, P.A., Nathan, C.F. and Gabay (1990) J. Clin. Invest. 85, 904-915
  3. Albrich, J.M. and Hurst, J.K (1982) FEBS Lett. 144, 157-161
  4. Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D.S., Weinrauch, Y. and Zychlinsky, A. (2004) Science 303, 1532-1535
  5. Beiter, K., Wartha, F., Albiger, B., Normark, S., Zychlinsky, A. and Henriques-Normark, B. (2006) Curr. Biol. 16, 401-407
  6. Kerr, J.F., Wyllie, A.H. and Currie, A.R. (1972) Br. J. Cancer 26, 239-257
  7. Fadok, V.A., Voelker, D.R., Campbell, P.A., Cohen, J.J., Bratton, D.L. and Henson, P.M. (1992) J. Immunol. 148, 2207-2216
  8. Colamussi, M.L., White, M.R., Crouch, E. and Hartshorn, K.L. (1999) Blood 93, 2395-2403
  9. Usher, L.R., Lawson, R.A., Geary, I., Taylor, C.J., Bingle, C.D., Taylor, G.W. and Whyte, M.K.B. (2002) J. Immunol. 168, 1861-1868
  10. Ottonelo, L., Cutolo, M., Frumento, G., Arduino, N., Bertolotto, M., Mancini, M., Sottofattori, E. and Dallegri, F. (2002) Rheumatol. 41, 1249-1260

Cholesterol treatment used in treatment of hepatitis C?

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By Kathryn Higgins

A molecule that is known to take up cholesterol into a cell has recently been identified to allow entry of the hepatitis C virus (HCV) into liver cells. This may lead the way for new therapies to be developed.

Hepatitis C is a disease that primarily affects the liver. It is caused by HCV, which is spread by blood-to-blood contact. Once infected, HCV can persist in the liver causing scarring and ultimately leading to liver failure or cancer. The World Health Organisation (WHO) estimates that three per cent of the world’s population (about 170 million) have hepatitis C, and although treatment is available, more effective therapies are needed. Liver transplantation is one such treatment, but infected patients find the virus attacks the new liver.

Previous studies have shown the involvement of cholesterol in HCV infection, thus it was hypothesised by researchers at the University of Illinois at Chicago that a cell surface molecule (a receptor) called Niemann-Pick C1-like 1 (NPC1L1), which is known to facilitate the uptake of cholesterol into the cell, may also be involved in trafficking the virus into the cell.

The research team headed by Susan Uprichard, assistant professor of Medicine, Microbiology and Immunology, conducted experiments to determine the role of NPC1L1 on viral uptake. Experiments involved blocking the receptor and reducing expression by using knock-out models. The results demonstrated that blockade or knock-out of NPC1L1 impaired liver cell infection with HCV.

To confirm these studies further, an inhibitor of NPC1L1 called ezetimibe, which is clinically used to lower cholesterol levels, was also tested. Results validate previous findings showing blockade of HCV uptake into the cells and preventing infection.

Current drugs used to treat hepatitis C are known to be toxic, and cannot be used by transplant patients, therefore ezetimibe may provide a solution as a new anti-hepatitis agent. Therapy with ezetimibe alone or in combination with current drugs may improve patient treatment by targeting the receptor NPC1L1 and preventing HCV entry into liver cells.

Reference:
Sainz et al, (2012) Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nature Medicine. Ahead of print.

The paper can be found at: http://www.nature.com/nm/journal/vaop/ncurrent/pdf/nm.2581.pdf

Ancient Humans: Becoming human

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There can be only one

No I’m not referring to Highlander I am referring to species of humans. Out of many species that fall under the umbrella term of the genus Homo we are the only one that has survived- Homo sapiens. The mystery behind this has had religious, philosophical and scientific ramifications over the ages that have been debated to this day. But who were these other humans? And can we really consider them to be human?

From the archaeological record we know a fair bit about these other humans which may be able to tell us just how human they were by identifying sociality, intelligence, technology and culture.

Homo habilis Stringer and Andrews 2005 P. 68

Robin Dunbar found a relationship between a part of the brain known as the neo-cortex and theory of mind. Theory of mind refers to a level of sociality- the first level dictates that person A knows something about person B. The second level dictates that person A knows that person B knows something about person C; and so on. Therefore the higher the level, the higher the capacity for an individual to comprehend what a group knows. This type of intelligence becomes important when we start to consider how a group functions within a landscape; they form social bonds which is crucial for group activity. Seeing this hallmark within primates, Robin Dunbar extrapolated the size of the neo-cortex within extinct humans from archaeological remains, and use it to infer upon theory of mind and sociality. What he found was a general clumping of all the extinct Homo species around the Homo sapiens mark. The lineage that led to the genus Homo diverged 6 million years ago from chimpanzees. The first Homo species that appeared on the scene was Homo habilis at 3 million years ago. It is very likely that by then, H. habilis had the intelligence to understand social situations.

While H. habilis was the first Homo species to make and use tools (which led to their alternative and rather informal name Handy Man), Australopithecus afarensis was actually the first species to do so. A. afarensis was an earlier species that walked on legs as opposed to knuckle-walking, and it is possible that the Homo lineage came from this species. The earliest evidence of tool use on bones comes from Ethiopia dated at 3.39 million years ago where it is known that A. afarensis inhabited this region. Clearly by the time of H. habilis, we start to see the beginnings of a rather primitive form of intelligence that enabled them to form social groups and use their own type of technology, which was known as the Oldowan tool industry.

Nariokotome Boy. Stringer and Andrews 2005 P. 139
Homo erectus

Eugene Dubois, a Dutch palaeo-anthropologist, was in Java (S.E Asia) in 1890 when he found a set of skeletal remains. He had found what was later called Homo erectus. This species was clearly the first member of the Homogenus to have migrated out of Africa. One of the most important finds belonging to this species was Nariokotome Boy found in Kenya in 1984. What was particularly interesting about this find was that the individual was thought to be just a little bit older than 11 years old and, from his remains, it could be seen that he was about 6 foot tall! This is a species that was very well adapted to the hot climate of Africa; H. erectus was tall, gracile and slender with long legs that enabled them to travel for long distances, which ultimately they did.

 

Homo heidelbergensis
Neanderthals

To perfectly complement how H. erectus was adapted to the hot climate of Africa, H. heidelbergensis illustrates adaptations to a cold climate. Likely to diverged from H. ergaster as well (and thus be a sister group to H. erectus), H. heidelbergensis was the last common ancestor of Neanderthals and modern humans. But it was also the first Homo species to move into Europe. The commonly held theory is that H. heidelbergensis evolved into Neanderthals in Europe. As such Neanderthals appeared to be very well adapted to the cold; they were short, stocky and well-built when compared to the tall and more graceful modern humans.

They had a wide distribution across Europe and Asia; from Israel to Wales, and as far north as Siberia and south as Gibraltar. Vast amounts of archaeology have shown that Neanderthals had their own culture and technology, and existed together in their own social groups. But all good things come to an end. By the time the Neanderthals had settled into their life in Europe, at 60,000 years ago, the climate got severely worse. Before the start of the Ice Age at approximately 28,000 years ago, modern humans had already arrived and settled themselves, and the Neanderthals had become extinct.

Cave painting from France
Figurine from Germany

The arrival of modern humans into Europe from 50,000 years ago is part of the next hallmark in our evolution: the Upper Palaeolithic Revolution. This revolution saw a cultural explosion. A wide variety of art has been attributed to the Upper Palaeolithic. Such examples include ornaments, figures and cave art, but it also included technology for acquiring and processing food. While the Neanderthals had their own technology for the same reasons, modern humans had a much more diverse toolkit. But as far as we know, no art found has been associated with Neanderthals.

In 2010, DNA analyses suggested that Neanderthals and modern humans interbred just outside of Africa before modern humans spread around the world. Following on from this, a few other studies have suggested that interbreeding was occurring between other human species, such as between H. erectus, and a possible new human species the Denisovans, and between modern humans and the Denisovans. While many more analyses need to be done to confirm this, this claim has immediate implications as to what we consider a species. A species is defined as a group of individuals that can only reproduce with each other. If Neanderthals and modern humans were interbreeding with each other, then this suggests that Neanderthals and modern humans are the same species, and that we (current modern humans) are descended from this interbreeding. More work however needs to be done. Ancient DNA is a field fraught with difficulties but as DNA technology improves we will have more data to look at.

By now we see a picture emerging as what we could consider as “being human”: the capacity for sociality and intelligence, use of technology and the element of culture. At the same time the lines between these various humans are beginning to blur. If the DNA evidence holds up, as more studies are carried out, then perhaps we should start to consider all of these humans under just one species name and designate each one by sub-species. The archaeological evidence certainly suggests that many of these types of humans had a level of intelligence that meant they could establish technology and culture which appears to be just as different from each other as they are morphologically. We are so willing to find the point in time where we can say “here is where we became human!”  The truth is we can’t. We, Homo sapiens, may have arisen around 200,000 years ago, but humanity could have begun much earlier. So when natural selection and bad luck killed off the other types of humans, it left us- the sole human survivor. This then leaves us with just one question:

For how long, in this changing world, can we survive?

For more information:

  • Dunbar, R. 2003. The Social Brain: Mind, Language and Society in Evolutionary Perspective. Annual Review of Anthropology 32, 163-181
  • Green et al. 2010. A Draft Sequence of the Neandertal Genome. Science 328 (5979) 710-722
  • Stringer, C. Andrews, P. 2005. The Complete World of Human Evolution. Thames and Hudson, UK.
  • Oppenheimer, S. 2004 Out of Eden. Robinson, London

This article was written to complement the presentation “Ancient Humans: Who were they? And who got it on?” that was given on the 5th December 2011 for the Natural History Society. For more details on the author, see http://independent.academia.edu/DanaeDodge

 

Transparent tissues offer a window into the brain

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By Kathryn Higgins

 

A revolutionary reagent has been developed that can literally turn biological tissues transparent. Researchers from the RIKEN Brain Science Institute in Japan have developed a reagent which allows 3D imaging of the neuronal network deep inside a mouse brain.

Imaging and labelling of cell populations deep within tissue has been a challenge for scientists for many years. Although advances have been made in cell imaging there are still many obstacles to overcome. Tissues often have to be sliced 1mm thick for viewing under a microscope to dissect networks since imaging within deep tissues leads to many problems due to the lack of transparency of the tissue. Several clearing solutions have been developed but these have disadvantages such as expense and quenching of fluorescently labelled proteins that are often used in cell research to visualise the structures.

A research team led by Atsushi Miyawaki, however, have recently developed a reagent, after a chance observation, which may revolutionise deep tissue imaging by obtaining 3D images that are valuable for improving our understanding of biological organisms and how they function.

The reagent, called ScaleA2, is a highly effective clearing reagent, greatly improving the transparency of tissues, and stabilising fluorescently labelled proteins. This allows imaging to be done at a much greater depth than currently possible, providing detailed 3D visualisation of neuronal networks within the brain than has ever been managed before.

Current research using ScaleA2 was done using dead embryo tissue for imaging neurones and blood vessels deep inside the mouse brain. Miyawaki and his research team, however, believe that the scope for using ScaleA2 in other tissues and organisms is not limited, and are currently trying to optimise the reagent for use in live tissue. This would open the door to experiments that have never before been possible.

 

Image shows two murine embryos. The left embryo was placed in PBS, whilst the embryo on the right was incubated for 2 weeks in ScaleA2 solution.

 

 

Reference:

Hama et al, (2011) Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain. Nature Neuroscience. Ahead of print.

The paper can be found at:

http://www.nature.com/neuro/journal/vaop/ncurrent/pdf/nn.2928.pdf