I mentioned a little while ago that I had been published on The Scientista blog, with an article titled, “The Matching Game”. For those interested, here is a link to the original post.
I mentioned a little while ago that I had been published on The Scientista blog, with an article titled, “The Matching Game”. For those interested, here is a link to the original post.
Gut bacterial flora is the complex community of microorganisms that live in the digestive tract of many animals and insects. In humans, the gut contains the greatest number of bacterial species and is established at one or two years of age. The relationship between an individual and their flora is an important symbiotic one, and changes in the specific make-up can have noticeable physiological effect on the human.
Some human gut microorganisms aid the host by fermenting dietary fibre into short-chain fatty acids (SCFAs), while others play a role in metabolising bile acids, sterols and xenobiotics and synthesising vitamin B and vitamin K. The biological importance of these compounds is similar to that of hormones, and, therefore, dysregulation of the gut flora has been correlated with a number of inflammatory and autoimmune conditions.
Moreover, for the past few years, it has also been known that gut bacteria can have an effect on our emotions. In fact, some species produce the same molecules as those that are used in brain signalling, such as dopamine, serotonin and gamma-aminobutyric acid (GABA). Since the brain is predominantly made up of fats, the SCFAs produced by the metabolic activity of bacteria also influence neural health.
Research conducted in 2011 by a team at North Carolina State University showed that a type of gut bacteria, called Lactobacillus rhamnosus, can dramatically alter GABA activity in the brains of mice, as well as influencing how they respond to stress. Their work illustrated that chronic treatment with L. rhamnosus “reduced stress-induced corticosterone and anxiety- and depression-related behaviour”.
Recently, work done by Philip Strandwitz and his team at Northeastern University in Boston has brought a new gut bacteria, KLE1738, to light. They discovered that this strain would only grow in the presence of GABA. Since GABA acts by inhibiting signals from nerve cells and low levels are linked to depression and mood disorders, this discovery further supports the hypothesis that gut flora affects brain function.
It has been suggested that further research into the link between gut microorganisms and neural molecules may eventually lead to new and personalised treatments for disorders such as depression and anxiety. While a search for a “cure” may be somewhat far-fetched, improved understanding may have a significant on improving patients’ quality of living.
A small community in the Dominican Republic has been in the news recently due to a BBC programme called ‘Countdown to Life’, which explores “how we develop in the womb and how those changes, normal and abnormal, impact us later in life”.
For the boys in this community, abnormal changes in the womb significantly impact their lives. Known as “Guevedoces”, translating to “penis at twelve”, these individuals, although male, do not develop the male sex organs until they hit puberty. The team filming the series were in direct contact with a number of boys currently undergoing the transition. Nearly all are dressed and treated as girls for the first decade of their lives, as there is usually little to no indication of their male gender. However, many seemed to know that they were boys and did not feel comfortable dressing in girls’ clothing or playing with stereotypically girls’ toys. Later, there were reports of bullying at school when ‘girls’ returned from the summer with a new name and a new wardrobe.
But, what is the reason for this delayed development? The condition was originally studied by Dr Julianne Imperato-McGinley, from Cornell Medical College in New York in the 1970s, who discovered the genetic reasoning behind this disorder. In the womb, in order to develop into a male, the foetus must convert testosterone into a more potent hormone called dihydro-testosterone, which transforms the tubercle into a penis. If this hormone isn’t produced, then the tubercle forms the clitoris instead. The Guevedoces are genetically deficient in an enzyme called 5-alpha-reductase, which normally converts testosterone into dihydro-testosterone, and therefore are born with vaginas rather than penises, despite being male. At puberty, like other boys, there is a second surge of testosterone in the body, and this time the body responds by growing muscles, testes and a penis. This genetic condition is quite common in this part of the world, but “vanishingly rare” everywhere else, probably due to a bottleneck effect caused by migrating ancestors.
An extremely interesting observation that Imperato-McGinley made was that, despite being brought up as girls in their childhood, almost all these boys showed heterosexual tendencies. Consequently, she concluded in her paper that hormones in the womb matter more than rearing when it comes to your sexual orientation. This is still a controversial topic and much discussed worldwide, especially with regards to the same-sex marriage laws in recent years. However, it may be that this small group of boys in the Dominican Republic are only strengthening the idea that gender identity depends on what’s within, not what’s visible.
Biomimicry is “the design and production of materials, structures, and systems that are modelled on biological entities and processes”. The invention of Velcro in 1941 was propagated when the Swiss engineer George de Mestral removed burrs from his dog’s fur and decided to take a closer look at how they worked. He was intrigued by the small hooks at the end of the burr needles, and realised that this had the potential to be developed into an easy-to-use material.
Now, biomimicry is being employed in reverse, with artificial biological materials being inspired by Velcro, itself. At the University of Toronto, Canada, Tissue-Velcro is being developed in order to provide a way to bind strips of cells together and make ‘living bandages’ for the heart.
This technique involves growing cardiac (heart) cells on two meshes: one covered with tiny hooks, the other with complementary holes. When placed in contact, the two meshes snag and allow tissues to be built up. The team at Toronto found that single layers of rat cardiac cells started contracting of their own accord on the mesh after only four days. Furthermore, stacks of cells growing together were found to start contracting with the same rhythm, hence opening up possibilities of using Tissue-Velcro to seamlessly repair damage caused to heart tissue by heart attacks or external wounds.
The design flexibility of this product is also an exciting aspect to this research. “Each case that a surgeon would be presented with is going to be unique,” said team member, Miles Montgomery. “You could build it in situ, almost like designer tissue.”
Hence, the group plans to seek regulatory approval for human use soon. Montgomery also suggests that this could lead to similar techniques to grow and repair “other complex tissues, such as skin or liver”.
However, as Jay Zhang of the University of Minnesota, Minneapolis raised, “The real test is how it works in vivo, to repair hearts, to repair vessels, to repair valves.”
I’ve spent my entire summer so far engaging in a variety of music activities, from giving recitals, to attending the Latitude Music Festival, to a three-week String Academy in Switzerland. But, despite the long tiring days, I have felt a sense of calm and happiness throughout the last couple of months. This may be due to the fact that I have been partaking in what I love, with people I enjoy the company of. And, it partly is. However, probably more likely than not, the constant exposure to music that I enjoy has increased my happiness levels at a chemical level, leaving me feeling far more relaxed than would be expected.
But, how is that possible?
It all comes down to dopamine, a neurotransmitter in our brains that is released when we satisfy our desires. It is sometimes labelled the ‘pleasure chemical’, enabling us not only to see rewards, but also to take action to move toward them. A study conducted by neuroscientists, Anne Blood and Robert Zatorre, at McGill University, Canada in 2001 showed that listening to pleasurable music activated brain regions called the limbic and paralimbic areas, which are connected to “euphoric reward responses”, like those we experience from good food, sex and drugs.
The release of dopamine after food or sex makes sense evolutionarily, as this reward makes us crave more, and therefore contributes to successful survival and reproduction. But, why would the presence of music, which, at first glace has no survival value, cause the same reaction?
Cognitive scientists still predominantly use a theory that was proposed in 1956 by the philosopher and composer, Leonard Meyer. He drew on theories that suggest that emotion rises when we are unable to fulfil some desire, creating frustration and anger. And then, when this craving is satisfied, the chemical reward is even stronger. Meyer hypothesised that this mechanism is at work when we listen to music. The patterns set up a sense of unconscious expectation in our musical minds, and if we are correct, the brain rewards itself by releasing dopamine.
As we become more trained in certain genres of music, our brains improve at anticipating the patterns, leading to an increased number of dopamine boosts. Maybe, I have been feeling so happy because I have been improving this skill due to concentrated musical training. Well, I would like to think so anyway!
Link to journal paper: http://www.pnas.org/content/98/20/11818.full
Apologies for the lack of new posts recently, but I have been so busy with writing for competitions, as well as participating in as many music courses over summer as possible.
In fact, I have recently been awarded a runner-up prize in the Scientista DiscovHER Writing Competition, which means that my entry will be posted on the DiscovHER blog. The aim of the competition was to celebrate female scientists and their research. Therefore, I wrote about Dr Elaine Hatfield’s work on the matching hypothesis, an extremely interesting theory and piece of work. This also means that I am going to be added to their list of regular bloggers, giving me the opportunity to write about a range of possible topics each month and have my work posted on their blog.
I am going on another music course tomorrow, but will be sure to write another post when I return in a week. I cannot wait to read up on and write about current research that has been happening while I have been away in Switzerland!
Narcolepsy UK describes narcolepsy as a “relatively rare sleep disorder which affects the brains’ ability to regulate the normal sleep-wake cycle”. This can lead to symptoms such as disturbed nighttime sleep and excessive sleepiness throughout the day. The website explains this by stating, “Normal sleep is organised into a regular pattern of REM (Rapid Eye Movement) and non-REM stages. Every 90 minutes or so, a normal sleeper experiences several minutes of REM sleep where dreaming occurs before switching back to non-REM sleep. In narcoleptic sufferers however, the nocturnal sleep pattern is much more fragmented and they typically experience numerous awakenings. REM sleep can occur very quickly during the night or day, producing unusual phenomena such as hallucinations.” Narcolepsy develops when the immune system destroys 70,000 neurones in the hypothalamus of the brain, which produces hypocretin – a neurotransmitter that carries a “waking signal’ to other parts of the brain.
Being very rare, narcolepsy normally only affects less than 5 in 10,000 people. However, this disorder has been in the news a lot recently, due to its unexpected link with another disease: swine flu. It was recently discovered that the swine flu vaccine caused a number of people to develop narcolepsy. However, it was not clear what in the vaccine brought about this change.
So, Emmanuel Mignot, at Stanford University School of Medicine, looked at the activity of CD4 cells, which form part of the immune system, in children who received the Pandemrix swine flu vaccine during the 2009 pandemic. He tested 39 narcoleptic children and their siblings – their identical twin siblings in four cases – who also received the vaccine but did not contract narcolepsy. He found that the children with narcolepsy had CD4 cells that reacted to both hypocretin in the vaccine and to a specific part of the HA surface protein unique to the flu virus involved in the 2009 pandemic. On the other hand, CD4s from the children that did not have narcolepsy did not react to either.
Furthermore, narcoleptic children who were given the 2012 flu vaccine, which, like Pandemrix, also contains the HA protein from the 2009 virus, also responded with a surge in CD4s that attack hypocretin and the cells that make it. Therefore, immunity to the 2009 HA protein, either in Pandemrix or in flu virus itself, had unexpected consequences for hypocretin production.
This is an exciting discovery because, as Mignot explains, “For the first time we have a clear environmental factor leading to an autoimmune process in some people. Genetics, immune history and environment have been hard to unravel in complex autoimmune conditions like diabetes. This system could lead to progress far beyond narcolepsy”.
Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterised by small platelets that are removed by the spleen, leading to a low platelet count. It is caused by mutations in a gene on the short arm of the X chromosome, and is therefore mostly seen in boys. This gene codes for the production of the WASp protein, which promotes and is mainly expressed in hematopoietic cells. Symptoms include easy bruising, spontaneous nosebleeds, recurrent eczema, thrombocytopenia, immune deficiency, and bloody diarrhea. Due to decreased antibody production, most WAS children suffer from at least one autoimmune disorder, and cancers (mainly lymphoma and leukemia) develop in up to a third of patients.
Now, researchers at Great Ormond Street Hospital, London, and Necker Children’s Hospital, in France, have used tamed HIV in order to replace mutated DNA in sufferers with the correct sequence. The principal treatment for this disease at the moment is bone marrow transplant, but that is only possible when the donor is a very close relative, such as a sibling. This new research, published in JAMA, provides an alternative option.
The doctors removed part of the children’s bone marrow and purified it in order to isolate the hematopoietic cells. A harmless strain of the HIV virus was then used to “infect” the cells with the normal DNA, monopolising on its invasive tactics in the human body. The treated bone marrow was then transplanted back into the children. As the bone marrow was originally taken from the child’s own body, it will not be recognised as “foreign” by the immune system, and therefore any concern of an immune response is removed.
In these trials, the therapy was successful in all the boys who participated in the trial, reversing symptoms and significantly reducing the amount of time they spent in the hospital. In fact, BBC reports, “one French child with severe autoimmune disease no longer needs a wheelchair”.
Following on from my post last week, where a genetically modified polio virus was curing brain tumours (https://darwinsbeard.net/2015/04/10/infecting-cancer/), it seems that despite on-going protestations concerning the use of gene therapy, this technique is rapidly progressing in the medical field. As Professor Adrian Thrasher, from Great Ormond Street Hospital, said, this trial is “another clear and powerful demonstration that a gene therapy approach is an effective one”.
It will be extremely exciting to observe how this treatment path will progress in the coming years. As Professor Ian Alexander from the Gene Therapy Research Unit at Sydney’s Children’s Medical Research Institute, Australia puts it, “the gene therapy field remains in its infancy, with the vast majority of its genuine promise yet to be realised.”
Research abstract available here: http://jama.jamanetwork.com/article.aspx?articleid=2275447.
I know that it has been a little while since I last posted, but I have just spent my Easter break in the Molecular Pathology Laboratory at the Universidad de La Frontera in Temuco, Chile. The students were kind enough to let me observe their experimental work and quiz them on their thesis; I was even given the very important task of extracting DNA from patient urine samples!
The lab is carrying out applied research in prevalent cancers in the Chilean population, namely gallbladder and breast cancers. As their website states, they focus “mainly on the molecular characterization of tumours and the identification and validation of biomarkers for susceptibility, early diagnosis, prognosis and response to treatment”.
During my time there, I discovered that they’re predominantly exploring unconventional methods of combating cancerous cells, such as photochemotherapy and inhibitory mechanisms to block signalling pathways between tumour cells and their environment.
So, I was inspired to do some reading around this area, and, in fact, discovered a very exciting episode of 60 Minutes called “Killing Cancer”, which aired on the 29th of March. Researchers at The Preston Robert Tisch Brain Tumor Center at Duke University, USA, have been carrying out Phase 1 clinical trials for an experimental cancer therapy. This treatment involves infecting tumour cells with the polio virus in order to trigger the body’s natural secondary immune response.
Cancer cells are usually invisible to the immune system, as they are not regarded as “foreign” by our white blood cells. However, the polio virus has “foreign” antigens on its surface that initiate an immune response, and as the virus is inside the cancer cells, the tumour is instead destroyed.
This polio virus has been genetically altered by Dr Matthias Gromeier, who replaced the aggressive polio-causing genetic sequence in its DNA with a harmless strand from a cold virus. This new modified virus can’t cause paralysis or death because it can’t reproduce in normal cells. However, in cancer cells it does, and in the process of replicating, it releases toxins that poison the cell.
Surprisingly for a Phase 1 study, this therapy has already cured patients with glioblastama, and Dr Gromeier has seen similar results in vitro with lung cancers, breast cancers, colorectal cancers, prostate cancers, pancreatic cancers, liver cancers and renal cancers. In about a year, the FDA is expected to make a decision on whether to grant Duke “breakthrough status”, which would make the treatment available to many more patients much sooner.
Breakthrough or not, it is still incredible that now, patients diagnosed with the most aggressive tumours can be cancer-free within two years of being treated with a single infusion of just half a teaspoon of polio.
Streptococcus pneumonia has been recognised as the major cause of pneumonia since the late 19th century. This bacterium also leads to the development of other infections such as, meningitis, bronchitis, septic arthritis and brain abscess.
Sounds awful, doesn’t it? Well, don’t worry; this bacterium is easily overcome by a good strong dose of antibiotics.
Or, is it?
Antibiotic resistant strains of pathogenic microorganisms are undoubtedly winning the evolutionary race against their susceptible counterparts. So much so, that the £10 million question posed by the Longitude Prize Committee in 2014 was, “How can we prevent the rise of resistance to antibiotics?” But, are we helping them?
I recently attended a talk as part of the Cambridge Science Festival, titled ‘Preventing the rise of antibiotic resistance?’, where leading scientists, Prof Dame Athene Donald, Prof Clare Bryant, Prof Andres Floto and Dr Mark Holmes, discussed and critiqued the rapid rise of the resistant pathogen.
The first antibiotic, penicillin, was discovered in 1928 by Sir Alexander Fleming, and began to be sold commercially in the 1940s, when it was developed by Howard Florey and Ernst Chain. In his Nobel Lecture in 1945, Sir Fleming predicted, “The time may come when penicillin can be bought by anyone in the shops. Then, there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug, make them resistant.”
Despite the warning, this is exactly what happened. Penicillin was marketed as a “superdrug”, and sold over the counter in every drugstore. And, by 1955, reports of penicillin-resistant bacteria had already started to flood in.
Professor Floto introduced an equation, which, I believe, entirely sums up the resistance problem.
Unregulated antibiotic use + environmental contamination + medical tourism =
a global problem requiring a global response
While only 5% of the Streptococcus pneumonia in the UK is antibiotic resistant, places such as South Korea and India are host to 100% resistant strains. Large-scale water supplies are contaminated by waste from hospitals. This waste often contains dregs of leftover antibiotics, elaborate concoctions that place a very high selection pressure on the bacteria living in the lakes, thus allowing any resistant strains to thrive. Then, when locals wash and bathe in these lakes, they become infected by these resistant bacteria, and are unable to be treated. Tourism is increasing the spread of these resistant strains, transporting them to uncolonised parts of the world, where they can once again thrive as their non-resistant kin are killed off.
In fact, no new types of antibiotics have been developed in the last 30 years. The blame has, so far, been projected on the government, which has neglected this issue, and big pharmaceutical companies, that much prefer to invest in more lucrative drugs, such as statins. One possible solution may be to start researching into non-conventional drugs, such as ones that target the host cell and cause autophagy, and the potential use of bacteriophages.
This on-going question, “How can we prevent the rise of resistance to antibiotics?” can only truly be resolved if the powers of the government, the pharmaceutical companies, the medical doctors and the research scientists are combined and translated into an international response.