Using CAR-transduced Tregs to suppress autoimmune disease

New research from a team of Israeli scientists has found that CAR-transduced regulatory T cells (Tregs) can be used to suppress autoimmune disease.

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In the images above, mice with colitis (inflammation of the colon, seen as the angry red blotches and nasty mucus in the ‘No Tregs’ image on the left) have much improved symptoms when they are infused with a population of immune cells known as Tregs (on the right). These immune suppressive cells act to dampen down T cell responses. Since colitis is caused by a patient’s own T cells reacting against protein targets like CEA (carcinoembryonic antigen) in the colon, Tregs can suppress these immune responses and restore a healthy colon.

This is the first time that immunotherapy has been used to dampen the immune system rather than hyperactivate it. To treat other diseases, like cancer, scientists prefer to remove Tregs and thus improve the activity of T cells reacting against tumour targets.

Image credit: Molecular Therapy and the Weizmann Institute of Science

Repost from the Stojdl Lab blog.

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Two Cancer Immunotherapy Targets are Better Than One

In cancer patients undergoing adoptive T cell therapy, T cells that recognise and react to an abundant protein fragment expressed by a tumour cell are infused into the bloodstream. These protein fragments are known as tumour-associated antigens.

Because cancers are so genetically flexible, when T cells start to attack a single one of these tumour-associated antigen targets, the tumour cells can quickly evolve a new way to grow that bypasses the need for this protein.

Now, mathematical models developed by researchers at Baylor College of Medicine in the USA predict that targeting two tumour antigens will improve T cell therapeutic reach and prevent tumour escape. Interestingly, though, these same models predict that targeting three will have no extra benefit.

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In the image above, the prevalence of seven common tumour associated antigens in the brain cancer, glioblastoma multiforme, can be seen across six different cancer specimens (UPN4-9).

Repost from the Stojdl Lab blog.

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Balancing modern and ancient anti-viral immunity

The human genome is stuffed full of ancient retrovirus genomes, a heritable legacy of ancestral infections. These pieces of DNA are dynamic elements, and can hop around the human genome and drive its ongoing diversification. Mostly, though, they are kept subdued by epigenetic changes that prevent them doing any damage.

While identifying threatening new viral genetic material is an important job for our innate immune system, there is typically no reaction against these ancient endogenous benign retrovirus cDNAs that in modern terms are essentially a part of our own genome.

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Yet scientists have now implicated this evolutionary trade off between the immune system being able to sense and react against infectious DNA viruses (like retroviruses, adenoviruses, herpesviruses) while staying quiet against non-infectious ancient viral elements in certain autoimmune diseases, like Aicardi–Goutières syndrome (AGS). In AGS, mutations in the Trex1 exonuclease enzyme allow non-infectious ancient retroviral nucleic acids to accumulate and cause heart damage.

They speculate that the immune system is almost inappropriately constrained against sensing these dangerous pools of foreign DNA, leading to autoimmune consequences.

Happily, though, there is a potential treatment: using reverse-transcriptase inhibitors to prevent the formation of ancient retroviral immunostimulatory cDNAs in the first place.

Image credit: Churchill Madikid

Repost from the Stojdl Lab blog.

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Using Viruses to Tune T Cell Functionality

As we have learned more about the world of microbes, it’s become clear that it’s possible to use bacteria and viruses as treatments against disease. But although microbes often work incredibly well at protecting against infections or attacking tumours, we still don’t really know exactly how they work.

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We know that our immune systems have developed ways to keep up with the devious tricks and schemes of microbes. When our cells become infected, the immune system activates a huge cascade of pathways, one of which leads to the activation of T cells against infected targets.

For T cells, forming a tight bond with these infected target cells is thought to be incredibly important in achieving a high-grade T cell killing performance.

Now, a team of scientists from the Chinese CDC has found that the tightness of the bond between a T cell and a target cell infected with vaccinia virus (administered as a therapeutic vaccine) relies heavily on the expression of the signalling molecule, MyD88. Surprisingly, it doesn’t rely much on the affinity of the T cell receptor, or the inflammatory conditions generated by the infection.

This exciting research suggests that vaccines capable of engaging the MyD88 pathway might perform better by tuning T cells to bind more tightly and kill more effectively their intended target cells.

Image credit: NICHD via flickr

Repost from the Stojdl Lab blog.

Posted in Bacteria, Cancer Immunotherapy, Disease, Health, Immunology, Microorganisms, Oncolytic Virus, Personalised Medicine, Science, Vaccines, Virology, Viruses | Leave a comment

Parasite proves proficient at immune scooping

As T cells bumble around our bodies, they are constantly on stand-by to recognise pathogenic target proteins. These pieces of protein are presented to T cells for inspection by other immune cells, known as antigen-presenting cells (APCs).

The T cells scoop up the pieces of protein being held up for inspection by the APC, along with a tiny bit of the APC membrance in a process known as trogocytosis. This leads to T cell activation and killing of infected target cells.

Now, scientists have discovered that trogocytosis is also used by the gastrointestinal parasite, Entamoeba histolytica, to chew away at individual host cells in the gut until they die. Once that happens, the parasite moves on to the next tasty cell snack. It also appears that practise makes perfect: the parasite refines its killing skills and becomes quicker at ingesting target cells as it spreads from cell-to-cell.

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Now we know that trogocytosis is involved in this nasty, potentially fatal gastrointestinal disease, we can begin to design therapies that block this pathway and stop the parasite in its tracks.

Image credit: Katy Ralston. The parasite is shown in green, while the target human cells are shown in fuschia.

Repost from the Stojdl Lab blog.

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Childhood obesity linked to poor vaccine protection

Obese adults are at a greater risk of getting infected by – and dying from – influenza viruses like the pandemic H1N1. So, it’s probably very important for obese individuals to get their flu shot each year.

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Yet interesting research coming out of the lab of Melinda Beck at the University of North Carolina at Chapel Hill is starting to paint a rather startling picture showing that obese people don’t develop good responses to vaccines compared to healthy weight controls. Antibody levels in the blood decline more quickly over time, and T cells don’t get as robustly activated or produce the same quantity of toxic molecules designed to kill invading pathogens.

Even more worryingly, these impaired vaccine responses are not just restricted to obese adults, but are seen in obese children as well. In Canada, an estimated 31.5% of children between the ages of 5-17 are overweight or obese.

Since a number of serious childhood infections, including measles and whooping cough, are on the rise, obesity could be a modern risk factor contributing towards the development of serious disease, potentially even in vaccinated individuals where primed immune responses just aren’t as good at dealing with infections.

Image: CDC/ Dr. Erskine. L. Palmer; Dr. M. L. Martin via Kat Masback

Repost from the Stojdl Lab blog.

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Leaky oncolytic viruses linked to better anti-tumour outcomes

There is currently a real push in the field of oncolytic virotherapy to create tightly cancer-targeted viruses that minimise side-effects in normal healthy tissues. Yet new research from North Carolina State University suggests that using a less stringently targeted virus might be better at achieving tumour control.

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It’s really important to generate large numbers of virus particles both at the beginning and end of oncolytic virotherapy. A huge burst of virus particles descending on the tumour gets the treatment off to an excellent start, and keeping virus levels high as the tumour shrinks ensures that no cancer cells escape.

The problem is that when the virus starts blasting through tumour cells, it is essentially removing a huge source of host cells – and thus its own capacity to replicate. On a practical level, this means that virus levels begin to decline with the tumour mass. Once the immune response becomes activated, the virus population slumps even further. This can allow tumours to relapse.

Happily, mathematical models predict that using a leaky virus that not only infects tumour cells but also a controlled number of healthy cells can maintain virus supplies. These mini virus factories could potentially be safely set up in organs like the liver that are capable of recovering by regenerating after virus infection.

Image adapted from Nature Reviews Immunology 9, 645-655 (September 2009)

Repost from the Stojdl Lab blog.

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Huge new database finds early transcriptional programs driving vaccine immunity

In recent years, scientists have made huge progress in furthering our understanding of how the immune system works, and applying this knowledge to vaccine design. Yet we are still pretty much in the dark about what makes a “good” vaccine. Are live replicating microorganisms better than dead ones? Is it better to generate an antibody or a T cell response? Are central memory or effector memory T cells better?

Big data promises to help us get to the bottom of these questions, and ten thousand others just like them. By analysing huge data sets, we can begin to tease out correlations and signatures that predict if (and how) a vaccine will protect against its designated disease.

Scientists at Emory University recently took the big data approach and created a hugely powerful database loaded with the molecular profiles of over 30,000 human blood transcriptomes from ~500 studies. They used this to look for a signature of protection across 5 successful human vaccines (2 against Neisseria meningitidis, 1 against yellow fever virus and 2 against influenza virus).

Since their tested vaccines varied in their nature – some were conjugate vaccines made up of two distinct parts, while some were live attenuated vaccines – it was tricky to come up with a universal vaccination signature between all 5 vaccines beyond the basics of “B cell activation” or “leucocyte differentiation”. Happily, though, it was possible to see similar signatures of immunogenicity within a vaccine class. For example, vaccines that had a large carbohydrate component tended to induce stronger T cell responses, while live attenuated vaccines upregulated larger innate immunity and interferon responses.

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In the image above, genes responding to each of the 5 tested vaccines (red, blue, orange, green, gray) are represented as segments of the circle. Bigger segments contain more differentially-expressed genes. A link between two segments indicates an gene overlap between vaccines.

Very interestingly, the team also observed that the two-part vaccines generated a dual-profile immune response established by two distinct molecular mechanisms.
Image credit: Li et al. 2013.
Repost from the Stojdl Lab blog.
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Exosomes may promote cancer spread after radiation therapy

Exosomes are small vesicles that are packed full of microRNAs, proteins, lipids and other biological molecules that get released from most cells in the body. In different biological settings, exosomes can be considered as little bubbles of joy or little packets of trouble.

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For example, in a normal healthy adult, exosomes help cells to remodel themselves and pass messages between cells. Yet in cancer cells, malignant exosomes can change how immune cells look and behave, and may promote tumour development.

Now, a team of scientists at the National Cancer Institute in the USA have analysed how radiation therapy affects the release of exosomes from either healthy or malignant brain cells. They found that radiation therapy increases the number of exosomes being secreted from both normal and cancer cells, and changes the nature of their proteomic payloads to promote cell motility. Such exosomes could play a substantial role in helping cancer cells to spread.

Image credit: Libertas Academica

Repost from the Stojdl Lab blog.

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A genetic blueprint of influenza virus

Currently, scientists can easily manipulate the genetic codes and epigenetic markers of viruses. This can help us to come up with innovative new ways to protect against serious pathogens like influenza virus, which can cause debilitating and even fatal infections.

But even though we’ve come a long way in flu vaccine design, we still rely on a lot of guesswork to predict which strains will arise in a given season, and haven’t yet been able to develop a one-size-fits-all vaccine. This is mostly because influenza is a genetically divergent virus that has a huge capacity to evolve and mutate.

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Now, a team of scientists at the University of California have taken a good hard look at influenza virus, and mapped out which genetic areas are absolutely critical for virus replication and survival. After deep sequencing ~98% of amino acids in the influenza haemagglutinin (HA) gene, they identified which areas can cope with – and ultimately benefit from – spontaneous mutations. More importantly, they identified which areas are indispensable for the virus life cycle, and have the potential to be simultaneously targeted by new super vaccines to prevent the emergence of escape mutations.

Image credit: CDC

Repost from the Stojdl Lab blog.

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Vaccinia virus infections guide new vaccine designs

If we mapped out the family tree of poxviruses, then vaccinia virus (the causative agent of cowpox) and variola virus (the causative agent of smallpox) would probably be sisters. Or at the very least, cousins. This close heritage allows the relatively benign vaccinia virus to confer variola virus-protective immune responses in vaccinated individuals.

A safely attenuated version of vaccinia virus, called modified vaccinia ankara (MVA), lies at the heart of the modern smallpox vaccine. Learning more about the biology of MVA helps us to understand why this vaccine is so great at protecting us from smallpox.

Scientists at Memorial Sloan-Kettering Cancer Centre in the USA have now discovered how MVA triggers innate immune responses during infection. They found that MVA DNA is detected by the immune sensors cGAS and STING, which activate secretion of type I interferons in a very specialised immune cell population – the conventional dendritic cells (cDCs).

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Yet vaccinia doesn’t passively accept the activation of these immune reactions that are designed to shut it down. Instead, it expresses a variety of virulence factors that inhibit these immune pathways and allow it to survive. This information could be used to improve the utility of MVA as a vaccine against other diseases, like cancer.

Image credit: Weltzin et al 2003

Repost from the Stojdl Lab blog.

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Creating immune silent biotherapeutic proteins

Our beautiful immune systems have evolved to efficiently recognise foreign objects – like bacteria and viruses – that aren’t supposed to be there. This activates a huge series of biological reactions that secure the threat and restore a safe environment.

Sometimes, though, the immune system reacts to things that it perceives as a theat, but are actually benign. This includes drugs and biotherapeutics that are being delivered to treat patients, but get blasted by immune responses before they get a chance to help.

Now, a team of scientists led by Chris King at the University of Washington in the USA have explored an interesting way to silence immune reactions against such foreign therapeutic proteins. They used computers to locate every immunogenic part of the protein (the T cell epitopes), and then predict a redesigned sequence that eliminated the immunogenicity but retained the protein activity.

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They used this method to successfully redesign two model proteins (GFP and Pseudomonas exotoxin A), and in future studies will use this approach to create immune silent proteins like factor VIII, a therapeutic protein for haemophilia A patients.

Image: The crystal structure of the factor VIII protein, Jacky Chi Ki Ngo

Repost from the Stojdl Lab blog.
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Convection currents help to deliver oncolytic virus in the brain

In a Phase I clinical trial for recurrent glioma run by the University of Alabama in the USA, 15 patients have received a steady stream of oncolytic reovirus (up to 10^10 TCID50) infused directly into their brain tumour. This novel method of infusion uses convection-enhanced delivery (continuous low-pressure catheter infusion) to deliver virus particles.

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The best responses were: 4 patient progressed, 10 patients had stable disease and 1 had a partial response. Some adverse events were reported, but none of these were considered serious.

Overall, reovirus was safe and well tolerated in the brain, and this newly tested method of delivery looks to improve how widely reovirus gets distributed across the tumour mass.

Image credit: NIAID via flickr

Repost from the Stojdl Lab blog.

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From tumour biopsy to personalised cancer treatment in 16 days

Every cancer patient essentially has a unique genetic disease. While certain key ‘driver’ mutations in genes such as TP53 and KRAS are almost always present, many other ‘passenger’ mutations are collected as tumours evolve that shape their genetic footprint.

These collections of mutations can lead to good or bad patient responses to treatment. Personalised cancer medicine aims to push a greater number of responses into the “good” category by using the genetic information from patient tumours to inform treatment choices. This strategy is already being used with some breast cancer drugs, such as Herceptin (Roche), where only ~30% of patient tumours express the right Her2 receptor target.

Whole exome sequencing (WES) is a computer-based method that catalogues patient tumour exomes – the part of their genetic information that gets translated into proteins. Yet WES has not been used extensively in the clinical setting.

Now, a team of researchers at Harvard Medical School, USA, have developed a clinical algorithm that translates the massive datasets generated by whole exome sequencing of tumour biopsies into a useful patient treatment plan. The algorithm is based on 121 target genes with potential relevance to tumour biology and clinical outcomes.

Your name hereAfter applying this algorithm across archived tumour biopsies from 511 patients, the team identified genetic alterations in their 121 target genes in 80% of patients. In a mini study to test the clinical utility of this approach, they generated personalised tumour genetic profiles for 16 cancer patients within 16 days, and used this information to siphon patients with certain exome mutations into matched clinical trials testing genetically complementary therapies. For example, one patient with metastatic lung adenocarcinoma exhibiting a KRAS-activating mutation (A146V) was enrolled in a phase I clinical trial of the CDK4 inhibitor, LY2835219 (preclinical data suggests a lethal relationship between activated KRAS and CDK4). This led to stable disease; the patient’s best and only clinical response to any cancer therapy.

Image credit: Swift Science Writing.

Repost from the Stojdl Lab blog.

Posted in Cancer Immunotherapy, Immunology, Mutations, Personalised Medicine, Science | Leave a comment

Blocking lethal viral haemorrhagic disease using interferons

Genetics can have a big impact on immune responses, making some individuals more suspectible to infections than others. In the world of small mammals, the virus LCMV-Clone 13 establishes a chronic infection in one mouse strain without too much damage. Yet in another mouse strain, the same virus activates a host T cell response that reacts so vigorously against virally-infected tissues that it kills the animal. Such deaths are often characterised by haemorrhagic fevers, where blood vessels start to leak, the body loses its ability to form blood clots and organs start to fail. Pathogens such as Lassa fever virus, Ebola virus and Dengue virus can cause haemorrhagic fever in humans, and represent a serious health threat.

Now, a team of scientists at the Scripps Institute in California, USA, have found that the immune cascade that leads to virus-induced haemorrhagic fever requires the activation of type I interferon signalling in non-haematopoietic cells. They found that simply administering antibodies that block type I interferon receptors could protect susceptible infected mice from developing serious pathological conditions, even though virus still persisted long after the antibody treatment had finished.

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This could represent a basic but incredibly effective approach for preventing deaths due to haemorrhagic viral disease. The one caveat is that the type I interferon blockade must be administered relatively soon after infection, since treatment efficacy declines over time, with 100% efficacy at 24 hours, 30% at 60 hours and 0% at 72 hours post-infection.

Image credit: VirginPrune on DeviantArt

Repost from the Stojdl Lab blog.

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Using pseudogene expression profiles to classify tumours & predict cancer prognosis

Pseudogenes are genes that have accumulated so many mutations that they can’t code for or create proteins any more.

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Now, scientists at the MD Anderson Cancer Centre have shown that characterising a cancer patient’s catalogue of pseudogenes can not only reveal what sub-type of tumour they have, but can also predict how they will respond to therapy and what their survival rate might be.

This creates an exciting new opportunity for the development of new prognostic tools that can potentially be used on a patient-by-patient basis.

Image credit: ynse via flickr.

Repost from the Stojdl Lab blog.

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Moving towards a universal immunosignature diagnostic platform for cancer

Scientists at Arizona State University have moved closer towards a universal immunosignature diagnostic platform for cancer.

Publishing in the journal PNAS, they describe the use of a platform that applies antibodies circulating in the blood of cancer patients to a large microarray of random peptides. Those antibodies that bind to one or more peptide are then characterised to create an “immunosignature” for each individual patient.

When the immunosignatures of multiple patients are compared, it becomes possible to pick out common peptides that keep cropping up. These could form the basis of a diagnostic test for cancer that would only require a drop of a patient’s blood. It may also be possible to use these peptide immunosignatures to inform the most effective type of cancer treatment.

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In the figure above, the expression levels of two immunostimulatory peptides are determined for 1516 cancer patients across 15 different cancer types. Peptide 1 shows high expression in 3 classes of cancer (10, 13 & 15), while peptide 1 is only expressed at high levels in 1 class of cancer (11).

Image credit: Stafford et al. 2014.

Repost from the Stojdl Lab blog.

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Digging into the soil microbiome of New York City’s Central Park

As the Summer looms and picnics become more the vogue, have you ever considered how many bugs live beneath the grass where you’ve spread your picnic blanket?

If you’ve gone off to a city park for your picnic, you might expect the number of bugs to be fairly low.

WRONG!

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Scientists investigating the diversity of the soil in Central Park in New York City took samples of soil every 50m across the 3.4km2 area. They used these soil samples to analyse the number and type of microbes living in the dirt, including bacteria, archaea and eukaryotes.

All together, they found 167,000 species! On average, each single soil sample had about 7000 bacteria and archaea, and 1250 eukaryote species.

Image credit: Ramirez et al. 2014.

Repost from the Stojdl Lab blog.

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Latest research​ suggests that the presence of Tregs might not be bad news for every type of cancer

Regulatory T cells, or Tregs, are immune cells that are typically considered bad news for cancer patients. That’s because these cells are immunosuppressive, and can prevent the patient’s own immune cells from attacking and clearing their tumour. Essentially, the Tregs are recruited by the tumour to act as a protective shield.
Yet new research from scientists in China suggests that Tregs aren’t always bad. In some cancers, the presence of many Tregs in the tumour can actually correlate with improved survival.

 

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Taken directly from their new paper, the risk graph above shows that patients with cervical, renal, skin, liver, gastric and breast tumours that were densley packed with FoxP3+ Tregs had a significantly shorter overall survival (their odds of survival, which is numerically considered along the horizontal axis, was lower). Yet increased infiltration of FoxP3+ Tregs was associated with an improvement in the odds of survival for patients with colorectal, head and neck, and oesophageal cancer.

Image credit: Shang et al. 2015.

Repost from the Stojdl Lab blog.

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Overexpressing Notch1 in regulatory T cells unlocks T cell proliferation

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Tumours typically recruit regulatory T cells (Tregs) to suppress the activity of other T cells. This effectively prevents T cells from targeting – and destroying – the tumour.

Now, a team of scientists from Harvard Medical School have shown that overexpressing a fragment of a protein called Notch 1 in Tregs reverses their activity – and helps them promote T cell function. Although this team’s research is based in a model of immune tolerance, it has key (positive) implications for cancer immunotherapy strategies.

Image credit: Scientific Illustration for the Research Scientist.

Repost from the Stojdl Lab blog.

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Blood pressure during treatment impacts oncolytic virus therapy

In an exciting new study released from the Mayo clinic, oncolytic vesicular stomatitis virus (VSV) was infused into mice with myeloma that had either just exercised (high blood pressure; ‘EX’) or were anaesthetised (low blood pressure; ‘ISO’).

Mice that had a higher blood pressure during intravenous perfusion showed a greater density of virus reaching the tumour site. Virus was also spread across the tumour in a more uniform pattern.

The mice receiving virus treatment at a higher blood pressure also had a significantly longer survival time (see graphs above; top=survival curves, bottom=individual tumour sizes).

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These results have potential positive implications for patients undergoing oncolytic viroimmunotherapy, since raising the blood pressure is easily achieved prior to virus infusion without the need for additional drugs or interventions.

Image: Miller et al. 2015Repost from the Stojdl Lab blog

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New tools promise life-saving treatments from basic science

Umberto Salvagnin : Flickr

If it’s done well, translational science can save lives. If it’s done poorly, millions of research dollars can be wasted. Image credit: kaibara87/Flickr/CC BY-SA

A mouse with cancer dies from a trial treatment that cured its genetically identical sibling. A stem cell in a dish has a different reaction than usual to a chemical cocktail and morphs into something unexpected.

This is the reproducibility crisis, and it is killing translational science.

New tools for critically reviewing research, created by researchers in the U.K., promise to tackle this crisis by pinpointing the flaws in the way we decide what is “good” data. They also promise to keep scientists on track and make sure only the most promising research moves towards the clinic.

Saving lives

If it’s good, translational science — that is, science that makes the jump from the lab into the clinic — can have a real impact on saving patient lives. If it’s bad, millions of research dollars can be wasted pursuing phantom treatments that should have ended up on the science scrapheap.

As a researcher in biology, immunology, virology and cancer, I’ve spent the last 13 years working at the lab bench and in the clinic. Now, I’m working on collecting and critically analyzing published research studies to make sure that the best drugs and treatments get licensed for patients.

Taking a deep dive

Scientific research typically falls into three camps: basic in vitro research (which is mostly done in a dish), pre-clinical in vivo research (that gets tested in animals) and clinical research (which is performed in patients). We already have a great technique to look at pre-clinical and clinical research to decide if it’s good enough to make it into patients, using a deep search and report approach called a systematic review.

A systematic review takes a hard look at the results from every high quality study that’s ever been published in a particular area of research and pools them all to produce a more powerful, overall conclusion about whether or not a treatment or technology is really effective —all the while minimizing bias and random error. Systematic reviews are used by national health boards around the world to decide whether new drugs or diagnostic tools can be approved for patient use.

But systematic reviews are hardly ever applied to basic research. This is a bit ironic, given that basic research is the foundation that every pre-clinical and clinical study is built upon. If basic research is undermined or unreliable, that means a disastrous collapse of the translational system that pushes new treatments into the clinic.

Flaws in the system

In a new paper, published in PLoS One, British researchers have highlighted some of the fundamental flaws that are going unchallenged in our research system when scientists fail to apply systematic approaches to their basic research. After investigating a test case — looking at how a cell’s machinery gets unequally divided after the cell splits in two — they found that just seven per cent of studies in this area could be considered reliable. Most were too ambiguous to be useful, and some were downright alarming. The team then custom built a brand new set of research tools to take a closer look at these studies.

One of the tools analyzed if a particular model system — from starfish, sea urchins, worms and fruit flies to mice, monkeys, humans and hamsters — was likely to produce a reliable answer to a particular research question. While most studies (61 per cent) used a relevant model, seven per cent were not fit for the purpose.

In one particular study, scientists claimed to have created a new type of stem cell-like model, but they never did a basic check to confirm that the cells behaved in a stem cell-like way.

Stem cells can divide into different types of cells – so it’s important to have good markers to fingerprint their offspring. Image credit: swiftscientist/pixabay

Another tool was designed to find out if the tags researchers used to shine a spotlight on different parts of the cell’s machinery were tested ahead of time to check that they were going to work. The outcome: most papers (57 per cent) never checked these key research tools before they started using them.

Inevitably, this led to some contradictory results. For example, one study used two different types of tag to highlight the same cell structure — the mitochondria, the powerhouse of the cell — and reported totally opposite results.

Research crunch

Perhaps most shockingly, 83 per cent of studies failed to include any basic internal checks: positive controls (which are designed to work every time), negative controls (which are designed to fail every time) and experimental repeats (which are designed to make sure the results are real). These are the most basic building blocks of scientific research. Every researcher gets drilled to include these when they start out in science. The fact that these are being missed so often — not just by the scientists themselves, but by the peer reviewers who comb through their papers before they’re published — is a truly alarming trend.

Encouraging basic researchers to apply more rigour in how they gather, analyze and critically evaluate the data they generate in the lab is an important issue at the very heart of research. New tools, such as the ones developed by this British team, will help researchers to systematically review their basic research findings before they get moved towards the clinic. They should also help to address some of the core issues that lead translational studies to fail, and millions of research dollars to be wasted.

Ultimately, these approaches will help “landmark” research findings, which are all too often wildly exaggerated in the current research climate, become a reality, and actually help the patients in the clinic who need them the most.

Originally published with The Conversation Canada.

Posted in Health, Medicine, Reproducibility, Science, Science Policy, systematic review | Tagged , , , , , , , | Leave a comment

Seafood offers up a mouthful of man-made garbage

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Public opinion is divided on the pleasure of consuming sea creatures that stare boldly back at you while you eat them. Like Marmite®, you either love it or you hate it.

Now, researchers at the University of California, Davis have added an extra level of complexity to this debate by showing that the seafood we eat regularly contains man-made rubbish that has made it out to sea.

The team caught and sampled a wide range of seafood from different ocean habitats – including fish (like anchovies, red snapper and tuna) and oysters – from Half Moon Bay and Princeton in California (USA) and Makassar on the island of Sulawesi (Indonesia).

At both these sample sites, around 1 out of every 3 fish or oysters contained litter. And over half of all the sampled fish species had man-made litter in their digestive tract.

(On the bright side, this suggests that gutting a fish before consumption should remove the litter-laden portion. But for fish and seafood that are eaten whole, it’s a very different story).

In Indonesia, most of this debris was plastic, including plastic fragments, foam and film. In the USA, the seafood was mostly full of textile fibres.

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Samples of the types of man-made litter sampled in seafood from sites in Indonesia and the USA. Modified from Rochman et al 2016.

This difference in the type of rubbish found in the seafood in the USA vs. Indonesia probably reflects the different styles of waste management in the two countries.

About 30% of solid waste generated in Makassar gets discarded straight into the ocean, so large plastic objects can easily degrade into small fragments and particles over time.

In California, over 200 waste processing plants dump treated effluent into the ocean, but these systems are not designed to remove synthetic fibres from washing machine runs – or a whole host of other complex drugs, like antibiotics and opiates. In fact, overhauling the waste management systems in countries around the world to deal with these issues, and ultimately provide safer drinking water, is a critical concern.

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This research highlights a real worry over the impact that eating these hidden seafood treasures could have on human health. This could range from physical trauma as detritus is inadvertently consumed, to the accumulation of toxic levels of pollutants up the food chain, to a lack of food security if seafood populations decline after eating our litter or swimming in our chemical-laden water.

Indeed, several organisations, including the United States Environmental Protection Agency (USEPA) and the United National Environment Programme (UNEP), have prioritised research into the effect that man-made debris has on the health of humans and their environment.

When you see the horrific pictures of the Great Pacific Garbage Patch, where artificial islands of man-made litter stretch out for hundreds of miles, it’s hardly surprising that hundreds of years of waste mismanagement are coming back to haunt us.

But it’s uncomfortable for it to stare up at us so boldly from our plates.

For more information, check out this great TED talk by Charles Moore.

Rochman CM, Tahir A, Williams SL, Baxa DV, Lam R, Miller JT, Teh FC, Werorilangi S, & Teh SJ (2015). Anthropogenic debris in seafood: Plastic debris and fibers from textiles in fish and bivalves sold for human consumption. Scientific Reports, 5 PMID: 26399762

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Kiss Me Under the Parasitic Angiosperm

Mistletoe - great for making single people feel unloved at Christmas.

Mistletoe – great for making single people feel unloved at Christmas. Credit: Agnes Kantaruk/Shutterstock.

Mistletoe is held in high regard at this time of year. No Christmas decorations are complete without a garland of cheerful mistletoe hanging on the door, or suspended prettily from the rafters as an incentive for festive romance.

In nature, though, many species of mistletoe, such as Viscum album, are actually parasitic pests. They plug directly into the veins of other plants, and shamelessly siphon off water and nutrients. Viscum album is a hemiparasite, so it gets most of its nutrients from tapping host plants this way, but it still dabbles in photosynthesis, the process whereby light energy from the sun is converted into chemical energy.

Since parasites use their hosts to do most of their biological work for them, they typically trim down their DNA to remove the genetic instructions needed for now-redundant tasks. Plant cells – like animal cells – contain two separate sets of DNA: in the nucleus and in the mitochondria. Nuclear DNA orchestrates most of the functions of the cell, while mitochondrial DNA generates the power to fuel these cellular activities. Roughly half of the genes encoded by mitochondrial DNA are dedicated to producing energy in the respiratory chain and the TCA cycle.

Genetic Mammoth or Mouse?

Although mistletoe is a parasite, the DNA housed in the nucleus of its cells paradoxically encodes one of the largest genomes found in angiosperms (flowering plants). Yet scientists at the University of Copenhagen have now shown that the DNA in mistletoe’s mitochondria is astoundingly genetically lean. In fact, Viscum album‘s mitochondrial genome encodes just 12 proteins*. To put this in context, Cycas taitungensis, an evergreen tree, has a comparatively mammoth mitochondrial genome encoding 41 proteins.

So, where did mistletoe’s mitochondrial genes go? Were they simply genomic dead wood that got the chop? Or did mistletoe never have a bulky mitochondrial genome in the first place? Scientists aren’t sure. But it’s possible that mistletoe has copied the approach that legumes like soybean and cowpea have taken: to jettison genes from the mitochondria and embed them in the nucleus, where they continue to work from a satellite location.

Gene Puzzle

Not only is the Viscum album mitochondrial genome peculiar because it encodes such a small number of proteins, but its genetic code is also so scrambled that it’s difficult to see how it could work properly. In fact, when you line up the mitochondrial DNA sequences of different plants, mistletoe genes are tremendously divergent, sticking way out on their own branch, thumbing their prickly haustorium at other plants (below).

Comparing the genetic sequence of three mistletoe species alongside other plants. Credit: Petersen et al 2015/Scientific Reports.

Comparing the genetic sequence of three parasitic Viscum mistletoe species alongside other plants. Credit: Petersen et al 2015/Scientific Reports.

Having said that, these jumbled genes probably do have roles to play: we just haven’t got to the point where we can understand their code or how they work. Otherwise, it would be difficult to explain how juvenile mistletoe survives before it latches on to its host plant, since mitochondrial genes are usually critical for sustaining life.

There’s certainly a lot more work to be done to understand the nature of mistletoe’s particular brand of parasitism and its seeming genetic mishmash. For now, though, it’s probably time to put the pipette down, sit by a crackling fire with a glass of eggnog in one hand and a mince pie in the other, and appreciate the simple festive cheer of this parasitic angiosperm.

 

* In the same study, two other parasitic mistletoe species, Viscum minimum and Viscum crassulae, were found to encode just 10 proteins; these represent the smallest number of proteins produced from a mitochondrial seed plant genome currently on record, beating the previous record holder, the white campion (Silene latifolia), at 25 proteins.

Petersen G, Cuenca A, Møller IM, & Seberg O (2015). Massive gene loss in mistletoe (Viscum, Viscaceae) mitochondria. Scientific Reports, 5 PMID: 26625950

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Fish oil capsules probably won’t boost your brain

fish oil for the brain

My mum and dad are troopers. Every morning, they down a tablespoon of fish oil in an effort to stave off old age and dry rot. And they do it without any obvious signs that swallowing a few millilitres of fishy oily stinky liquid is probably the worst way to start a morning. Clearly, they’re from a more stoic generation.

Since fish oils – or more accurately, the omega-3 long chain polyunsaturated fatty acids (n-3 PUFAs) in fish oils – have been linked to cognitive performance, the “lubricate the ol’ brainbox!” idea behind getting the stuff into your system has a lot of appeal. Especially when you’re trying to achieve literary perfection in your blog articles (disclaimer: no fish oil was consumed during the writing of this article). But, for some of us, the idea of choking it down in its liquid form is overwhelmingly repulsive.

Enter: fish oil capsules. On the surface, the perfect solution! The fish oil stays safely trapped in its hard shell until it passes down through the stomach and into the upper intestine. Once there, the capsule degrades enough to allow the brain lube to erupt.

There’s just one problem. New research led by Benjamin Albert at the University of Auckland in New Zealand shows that the quality of over-the-counter fish oil capsules is pretty rubbish. Albert and his team bought 32 different brands of fish oil capsules, and measured them for levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), supposedly the “good” n-3 PUFAs responsible for brain gains. They found that 69% (29/32) had lower levels of EPA and DHA than the companies claimed on the label (see the graph below). As an interesting side note, the more expensive capsules were more accurately labelled for EPA and DHA levels.

EPA DHA levels in fish oil capsules

To achieve such lower-than-advertised levels of EPA and DHA, either the freshly isolated fish oil had lower concentrations to begin with, or the oil within the capsule degraded over time. Both EPA and DHA are prone to oxidation, and break down to form a soup of peroxides, aldehydes and ketones. In fact, fish oil supplement manufacturers typically add anti-oxidants into their capsules to slow this process.

When the New Zealand team tested oxidation values across fish oil capsules, 92% exceeded one or more international recommendations. But older capsules that had been on the shelves for longer didn’t show any difference in oxidation values compared to newer ones. This suggests that there were lower levels of active EPA and DHA at the very beginning of the manufacturing process, and that many companies may be failing to test their individual batches of fish oil.

What might such oxidation values mean for the consumer? While some studies indicate that oxidation breakdown products may in fact be responsible for the anti-inflammatory benefits of fish oil, at high experimental doses, they can cause organ toxicity, stunted growth and accelerated atherosclerosis. The overall effect (if any) of consuming products with high oxidation values on health is still very unclear; hence, levels in fish oil capsules are subject to recommendations based on palatability rather than legal requirements based on safety.

If this research is representative of the global market, consumers have a 1 in 11 chance of buying fish oil capsules that contain robust levels of EPA and DHA. These odds might improve a little if they stick to high-end brands. All in all, until better standards and regulations hit the fish oil supplement market, it’s probably a good idea to look for your brain boost elsewhere.

Albert, B., Derraik, J., Cameron-Smith, D., Hofman, P., Tumanov, S., Villas-Boas, S., Garg, M., & Cutfield, W. (2015). Fish oil supplements in New Zealand are highly oxidised and do not meet label content of n-3 PUFA Scientific Reports, 5 DOI: 10.1038/srep07928

 

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Where should I send this darned manuscript, anyway?

As an academic scientist, this question usually hits you right after you’ve written your results section, but haven’t had a chance to square up to the pit of seething hell that is the discussion. It’s a blissful point where you can stop and carve out a moment to joyfully delay the inevitable. There are a few ways to choose which journal will have the honour of taking on your magnificent manuscript.

Nail, meet hammer

The bluntest approach is to go through your reference list manually, and compile a list of each journal as it appears, as well as the number of times it shows up. Shuffle these into the order of the most frequent, and you can easily pinpoint the top five journals in your manuscript. If you want to be extra fastidious, you can look up the impact factors of the journals in your list (or at least those of the top five), and factor those in, too. See my example below, written out on an extremely nice purple pad.

Manually Compiling a List of Potential Journals for Manuscript Submission

Online tools to the rescue!

A slightly more elegant approach is to use online tools created to solve this exact dilemma. My favourite is probably JANE: the Journal/Author Name Estimator, made by Martijn Schuemie from the Biosemantics group at Erasmus MC in The Netherlands. Pop your abstract into the search box, hit Find Journals, and prepare to be presented with a heady list of journals that have published articles similar to yours. These potential journals are ranked in terms of ‘confidence’, or how tight the match is between your input abstract and the past article output of that journal. While bona fide impact factors aren’t displayed, you do get provided with probably the next best thing: the Article Influence (AI) score. This measures the average influence of articles published from that journal based on how often they got cited within the first five years after publication. The AI score is weighted based on which journal is doing the citing – so a citation in a big impact factor journal, like Science, bolsters the AI score to a more significant degree.

JANE

If you don’t like the look of JANE, the Virginia Tech University Library has also compiled a list of other web-based tools that can help you find a nice good-looking journal to publish in.

Happy manuscript submissions!

Originally published on the Stojdl Lab blog

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Trials funded by rich patients could help find cures for us all

Bridging gaps in medical funding. Patrick Feller

Disease can affect any person, rich or poor. While your bank balance can’t really protect you from getting sick, it could potentially buy you – and many other patients – access to a better treatment for your disease. A new “plutocratic proposal” put forward by Alexander Masters enlists wealthy patients to both fund and participate in clinical trials alongside other patients who could benefit from an otherwise untested new treatment.

Developing a new treatment can be a long and expensive process that leaves promising new treatments languishing in a lab freezer. The translation of a treatment from the lab bench into humans can cost millions or billions of dollars. There are few grants that suit this type of research translation – and private donations, while very gratefully received, rarely add up to the right numbers.

If it is a disease that affects many, like cancer, then huge organisations, such as Cancer Research UK, can help lobby for grants to be directed towards clinical trials that will, on average, help more people. In such economic circumstances, those with rare diseases have a hard case to make for money to be directed their way.

This funding situation is only expected to get worse. For instance, the Canadian Institutes for Health Research (CIHR), one of Canada’s largest funding bodies for health sciences, is debating whether clinical trials should be funded at all. They argue that funding a single clinical trial with a price tag of C$2m (US$1.8m) – the approximate cost for an academic researcher to run their own early-stage study – would mean that many other research labs who might otherwise expect to receive smaller grants to support their basic research would miss out.

The main alternative path for finding funds to take that first step into a clinical trial pairs a researcher with a pharmaceutical company. The industrial partner supplies the necessary funds needed to run the study, as long as they see good potential for a return on their investment. The downside is that researchers usually end up signing away their promising treatment as a condition of the partnership – and ultimately losing control of subsequent returns should the therapy prove to be successful.

With Masters’ proposal, a rich benefactor essentially enables a clinical trial to go ahead that would otherwise have remained unfunded. The idea involves creating a not-for-profit “dating agency” that would match a sick benefactor with a researcher who has a promising new treatment for his or her disease.

The dating agency would have an independent panel of scientists whose job it would be to validate the science behind the therapy. The rich benefactor donates, say, US$2m and both the benefactor and 19 other people suffering from that disease, who could not have afforded to pay a contribution towards such a trial, get a spot on the clinical trial. The framework of the clinical trial – including ethical and regulatory approval – remains unchanged. The only difference is where the funds are coming from.

One version of Alexander Masters’s proposal. The Wellcome Trust/Peta Bell/Jean Jullien

Most importantly, Masters has shown that this funding approach works. After his close friend Dido Davies died from cancer after receiving traditional treatments that didn’t really help, Masters began exploring new ways to help patients get access to promising new drugs.

In just eight months, he had helped to secure £2m (US$3.2m) to get a new biotherapy for neuroendocrine cancer – Dido’s disease and the one that killed Steve Jobs – into clinical trials. This new biotherapy, a cancer-killing adenovirus developed in Uppsala University in Sweden, had been languishing in a freezer for several years because of a lack of funds.

Masters explains his idea:

There are 100,000 people in the world worth more than £20m (US$32m). According to the medical statistics, between three and five people in every 100,000 will get neuroendocrine cancer. So three to five supremely wealthy people will have the disease. For £1m, I was going to sell one or two of these wealthy individuals a place on the [biotherapy] trial. All the wealthy individuals had to do was pay for the entire trial.

Masters initially held a crowdfunding campaign to raise £200,000 (US$320,000) and generate enough publicity for his idea. As he had hoped, the campaign caught the attention of an American millionaire called Vince Hamilton, who was also suffering from neuroendocrine cancer. He supplied Uppsala University with the remaining funds to start the clinical trial.

Masters now hopes that this model can fund further trials. One of the golden features of his idea is that it shifts the return on clinical trials from profit – the aim of pharmaceutical industry-funded trials – to health. Masters’ new idea appears to be a scalable solution that could see plutocratic patients overhauling the currently listless clinical trial funding structure.

Originally published with The Conversation UK

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Tracking the Daily Microbiome

human microbiome by Hank Osuna

Human Microbiome by Hank Osuna

Humans are essentially 90% bacteria. These bacteria pepper our skin and hang out in our digestive tracts, helping to break down complex carbohydrates and keeping bad bugs in check.

We know how the human microbiome (our collection of bacteria) gets seeded during the birth process, and we know how bacterial populations change in the aftermath of a biological apocalyse, such as their human host taking a course of antibiotics. Yet we know very little about how the microbiome changes on a day-to-day basis.

Now, a team of scientists at Massachussetts Institute of Technology (MIT) have changed that by recruiting two individuals to provide samples of their poop and saliva every day for a YEAR to track their gut and oral microbiome signatures, and correlate them with lifestyle and activities.

Overall, microbe communities remained remarkably stable for months at a time. The three big variables – sleep, exercise and mood – failed to make much of an impact on microbe populations. Yet small dietary and lifestyle changes prompted rapid (next day) changes. Increasing fibre intake boosted populations of fibre-sensitive Bifidobacteria, Roseburia and Eubacteria. Bifidobacteria levels were similarly enhanced after eating live yoghurt cultures. Eating citrus fruits led to a jump in levels of Clostridiales bacteria, while dental flossing decreased saliva levels of the dental pathogen, Streptococcus mutans.

bacterial bodies bryan christie scientific american june 2012

Bacterial Bodies by Bryan Christie

The biggest changes in microbiome signatures happened in the wake of relatively rare life events. Travelling from a developed to a developing country caused numbers of Bacteriodes microbes to swell (as the host ate new foods) and increased Proteobacteria populations (as the host experienced bouts of diarrhea). These bacteria settled back down to normal levels when their host returned home. On the flip side, a bout of Salmonella food poisoning permanently wiped out a subset of native Firmicutes bacteria, which eventually got replaced by other similar species.

It appears, then, that our microbes generally go about their business in a happy, unpeturbed state. Yet inadvertently introducing them to a new experience can either result in a benevolent (often temporary) change, or a tremendously negative wipe-out event.

You can read the original #openaccess article free here.

David LA, Materna AC, Friedman J, Campos-Baptista MI, Blackburn MC, Perrotta A, Erdman SE, & Alm EJ (2014). Host lifestyle affects human microbiota on daily timescales. Genome biology, 15 (7) PMID: 25146375

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Plastic bags responsible for outrageous lack of cute pink piglets

Margaret Ackland, Plastic Bag, Oil on Linen

Margaret Ackland, Plastic Bag, Oil on Linen

Most of us now subscribe to the idea that plastic bags are bad for the environment. Hence, droves of people turn up at their local supermarket with a sturdy jute bag in tow. Now, there’s evidence that the items that get placed into plastic bags also have a terrible time, especially if they’re biological in origin.

Take the case of pig farmers in Spain. In Spring 2010, 41 farms across Spain reported issues with their lady pigs failing to get pregnant after artificial insemination. The ensuing biological detective hunt found that sperm quality was high (it was good and wriggly, and donated from several different boars, ruling out a genetic incompatibility) and the fertility of the potential mother pigs was good. All the animals were in good health, and they were kept in comfortable, well-fed conditions.

One of the factors that all the farms had in common was the brand of plastic bag being used to store the boar semen until it got pumped into the lady pig. In fact, the longer the semen was kept in these bags, the greater the decrease in fertility.

5327424325_ebeec43563_o

Plastic bags: a chemical cocktail

Concerned that a chemical contaminant may be to blame, scientists at the Universidad de Zaragoza passed an old batch of “good” bags and a new batch of “suspicious” bags through a mass spectrometer (a machine that breaks materials up into their chemical components). They found that the “suspicious” bags contained five extra chemicals that weren’t present in the “good” bags: 1) octyl phthalate, 2) 13-docosenamide, 3) BADGE (a derivative of Bisphenol A), 4) 1,4-trioxacyclotridecane-8,13-dione (a cyclic lactone) and 5) diethylene glycol cyclic phthalate. These chemicals formed part of the adhesive used to manufacture the multilayer bags.

Three of these chemicals (BADGE, 1,4-trioxacyclotridecane-8,13-dione and diethylene glycol cyclic phthalate) were actually capable of leaching out of the bags into the fluid they contained (sterile water was used as a less messy substitute for boar semen to find this out). Yet in a dish, mixing these three chemicals with boar semen had no impact on sperm quality: no obvious abnormalities were seen, and the sperm were still able to penetrate eggs in a fish.

Finally, the ultimate test was performed: if semen spiked with these three chemicals was infused into a lady pig, would there be an outrageous lack of cute pink piglets born? Sure enough, there was a drop in the fertility rate from 84% to 58%, and the number of piglets being born fell from 231 to 70.

About your plastic water bottle…

This study didn’t go as far as identifying exactly how these chemicals were messing up fertilisation: the authors speculated that blastocyst implantation or early development may have been affected. However it happened, though, this is definitely a cautionary tale for using plastic bags as storage containers, with significant relevance for human artificial insemination. The leaching of such chemicals into the environment as plastic bags break down on landfill remains a sure source of concern to humans and pigs alike.

Nerin C, Ubeda JL, Alfaro P, Dahmani Y, Aznar M, Canellas E, & Ausejo R (2014). Compounds from multilayer plastic bags cause reproductive failures in artificial insemination. Scientific reports, 4 PMID: 24810330

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The science behind FIFA’s footballs

Football_soccer_futbol_by_walexxx19Lovers and haters of the World Cup alike can’t fail to be amazed by the skills of some professional footballers. Like David Beckham or Cristiano Ronaldo. But while some footballers have been blessed by biology, it’s not just the combined genetic talent of a player or a team that leads to a stunning win or a sorry loss. According to scientists at the University of Tsukuba in Japan, the aerodynamic performance of a football can introduce a skill set all of its own.

The football has evolved substantially from its vaguely nauseating origins (an inflated sheep’s bladder) to the shiny polished orb in use today. A typical football is made from 32 five- and six-sided panels stitched together to form a pleasingly spherical shape. In recent years, this basic design has developed towards minimising the number of panels and changing the pattern in which they’re stitched together to boost aerodynamic performance and consistency. Adidas, who ride at the forefront of innovative football design, have created the Cafusa (32 panels; currently used by many football leagues), the Teamgeist 2 (14 panels; the official ball of the 2008 EURO cup) and the Jabulani (8 panels; the official ball of the 2010 FIFA World Cup). Now, for the FIFA World Cup 2014, they’ve made it to the 6 panel ball: the Brazuca.

The team of Japanese scientists wanted to find out how these different balls – the Cafusa, Teamgeist 2, Jabulani, Brazuca and the traditional Molten Vantaggio 32-panel ball – behaved in flight, and how this affected shot accuracy on goal. To do this, they employed a wind tunnel, a kick robot and a whole bagful of beautiful balls. To take into account the difference in panel stitching design, they looked at the ball’s performance when it was kicked off from two orientations: normal (head on) or tilted 180 degrees (see below).

balls

They found that the different balls experienced substantially different aerodynamic forces as they were “kicked” into the wind tunnel. The Brazuca was the most stable ball in flight, followed by the conventional ball, Cafusa, Teamgeist 2 and Jabulani.

When the balls were travelling at higher speeds (the equivalent of a good hearty kick, or a “power shot”), the Cafusa generated the biggest increase in lift and side force – which could allow the ball to travel a greater distance. The Jabulani put in the worst performance in this category, and behaved “irregularly” when it was in flight.

The scientists then launched balls from both orientations at 30m/s towards a goal 25m away, and plotted the hits on target (see graphs below; blue is head on, red is tilted 180°). The Brazuca and the conventional ball gave the best performances, hitting the target most consistently regardless of the orientation of the ball (the blue and red spots cluster together). For the Cafusa, the Jabulani and the Teamgeist 2, the flight paths and in-flight behaviour varied hugely depending on which orientation the ball was in when it set off towards the goal (the blue and red spots are far apart). Even when the number of panels were the same (Cafusa vs. Conventional ball; both 32 panels), differences in panel orientation and stitching design meant the conventional ball hit the target more consistently than the Cafusa.

accuracy on goalThese results – particularly the importance of panel orientation on performance – will undoubtedly be used to inform the design of the next generation of footballs with an eye to improving shooting accuracy and enhancing player performance. Ultimately, though, the conventional 32 panel ball performed just as well – if not better – than most of the innovative new footballs tested, suggesting that at some point it’s not that easy to improve upon design perfection.

Hong S, & Asai T (2014). Effect of panel shape of soccer ball on its flight characteristics. Scientific reports, 4 PMID: 24875291

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Watching it Burn: Soil Microbes vs. Wildfires

Los Angeles County "Station Fire" view from LAXWildfires can devastate ecosystems across the world. In 2012, over 67,000 wildfires raced across more than 9 million acres of land in the US alone. Fuelled by wind and parched vegetation, wildfires burn through everything in their path: plants don’t stand a chance, and even mobile animals struggle to outpace the flames.

But what impact do wildfires have on the beasties that live deep down in the soil? For example, soil-dwelling microbes, like bacteria? These incredibly important organisms help ecosystems to flourish, but their ability to recover after a forest fire – and to help other parts of the ecosystem recover, too – has been largely uncharacterised. Until now.

A team of scientists in China recently calculated that 70-80% of soil microbial biomass (the organic material made up of bacteria and fungi) was lost after wildfires swept through forests in the Greater Khingan mountains. But the flames didn’t fry the bacteria directly. Rather, the fire dramatically altered the soil biochemistry, most importantly changing its pH but also impacting moisture content, carbon/nitrogen ratio’s and ammonium levels.

This meant that the classes of bacteria that were more flexible at growing at an increased pH – like Bacteriodetes and Betaproteobacteria – were able to persist in the soil after the wildfire had swept through. The populations of other bacteria, like Acidobacteria, plummeted, since they were less equipped to grow in their newly scorched and acidified home.

It took 11 years for the original community of bacterial species to re-establish themselves. While this seems staggering, it’s actually a lot quicker than the above ground vegetation, which typically takes 20-100 years to reappear. Intriguingly, the bounce back of soil bacteria and the gradual re-emergence of a happy soil environment probably plays a huge role in the re-establishment of plants, and the animals that eat them.

This research may help to guide environmental efforts by aiming to adjust soil environments to help ecosystems make a speedy recovery after a wildfire.

Xiang, X., Shi, Y., Yang, J., Kong, J., Lin, X., Zhang, H., Zeng, J., & Chu, H. (2014). Rapid recovery of soil bacterial communities after wildfire in a Chinese boreal forest Scientific Reports, 4 DOI: 10.1038/srep03829

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Swimming with Viruses

8641509698_ac47920d89_bYou can find viruses everywhere: in the soil, in the clouds and in animals. According to scientists from the University of Oldenburg in Germany, there are also a ridiculous number of viruses buried at sea, in the sediments of the oceans.

These sedimentary viruses don’t lie dormant on the seabed, but actively replicate down in the fathoms, even in the gyres of the ocean where most forms of life can’t be sustained since organic carbon is a scarce commodity. By infecting and killing prokaryotic cells (bacteria, archaea) in ocean sediments, viruses act as efficient organic carbon recycling machines.

Scientists found that in every sediment tested, from active tidal flats, open oceans and nutrient-poor gyres, viruses vastly outnumbered prokaryotic host cells. Active viruses didn’t just exist in the oceanic topsoil, but rather permeated through deep layers laid down millions of years ago. Bacteriophages (viruses that infect bacteria) could be found in layers of sediment 320m deep, and in ancient layers from ~14 million years ago.

These exciting findings mean that viruses are actively replicating in buried ocean sediments all the time, and are thus making a huge contribution to the maintenance and carbon cycling of oceanic microbial communities.

Engelhardt T, Kallmeyer J, Cypionka H, & Engelen B (2014). High virus-to-cell ratios indicate ongoing production of viruses in deep subsurface sediments. The ISME journal PMID: 24430483

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More evidence that red wine and aspirin protect against cancer

4084992018_3ac2a6c037_b

Cancer is a disease of genes. DNA mutations mess with the genetic content of a cell, enabling it to escape the normal controls that restrict their growth.

Now, a team of scientists led by Delphine Lissa and Guido Kroemer at the French Institute of Health and Medical Research in Paris have begun exploring ways to slow or stop the formation of cells containing multiple copies of chromosomes, which they think are an essential intermediate in cancer formation.

Normal healthy cells are diploid, which means they have two copies of each chromosome, one from each parent. But during cancer formation, early malignant cells are often tetraploid, with four sets of chromosomes—the extras are either mistaken copies created in-house or genomes picked up from other cells.

Most cells deal with tetraploidy by committing suicide before they become malignant. These genomically deviant cells can also get removed by the immune system as part of its routine cancer surveillance program. But sometimes, these cells are not dealt with, allowing them to continue accumulating chromosomes and acquiring new genetic mutations, transforming them into dangerous cancer cells.

Enjoying that drink

In their study, published in the Proceedings of the National Academy of Science, Lissa and colleagues looked for drugs that could kill tetraploid cells, but leave healthy diploid cells relatively intact. After screening a panel of 480 bioactive chemicals from a database at Harvard Medical School, they came up with two hits: aspirin and resveratrol.

Aspirin is a common presence in the medicine cabinet, and has an excellent record against disease. Almost all of us have enjoyed its headache-relieving properties, and many old people are advised to take small doses of aspirin to protect their hearts. There is also evidence that aspirin can prevent colon cancer.

Those of us who enjoy red wine are ingesting resveratrol on a regular basis. It is also found in red grapes, peanut butter, dark chocolate, and blueberries. While it is still not certain exactly what protective effects resveratrol has against disease, there are suggestions that it can prolong lifespan, protect the heart, and prevent certain forms of cancer.

When researchers looked closely at the fates of both dangerous tetraploid or normal diploid cells treated in a dish with their two drug hits, they observed that unhealthy cells were controlled at least partially through the activation of signals that coaxed them into committing suicide.

Lissa also looked at the use of statins, which work through some biological pathways that may overlap with those tweaked by aspirin and resveratrol (they are commonly prescribed to control high cholesterol levels and minimise the risk of heart disease and stroke). In mixed populations of diploid and tetraploid cells, statins selectively induced more tetraploid cells to die. Several agents, then, could suppress the growth of genetically unstable cells capable of causing cancer.

Stopping cancer in its tracks

After establishing that their drugs had useful effects against fully-formed tetraploid cells, Lissa looked into whether the team could prevent such dangerous tetraploid cells from forming in the first place. Seems it can be done—resveratrol, aspirin, and their biochemical derivatives also reduced the formation of tetraploid cells.

When tested in mice prone to intestinal cancer, either oral resveratrol or aspirin lowered cancer rates. By probing gut cells with fluorescent tags, they saw that fewer dangerous tetraploid cells formed in treated animals. So both drugs could normalise the gut environment to minimise the likelihood of cancer.

2009-04-03T14-53-19 IMG_9796Out of the other 478 screened drug candidates, most had no differential impact on dangerous versus normal cells. Several other agents, including the chemotherapeutic agent cisplatin, the food supplement quercetin, and the herbicide paraquat, preferentially killed normal diploid cells but allowed the dangerous tetraploid cells to continue growing.

This study shouldn’t be viewed as justifying opening a bottle of red wine. Lissa didn’t investigate the effects of these drugs on normal cells that are meant to contain more than two pairs of chromosomes—certain cells in the liver, heart, immune system, and reproductive organs all normally have extra chromosomes. Also, aspirin may have limited use as a long-term anti-cancer agent due to its serious side effects (causing bleeds in the stomach). Finally, it’s not clear whether tetraploid cells are a necessary intermediary to cancer.

Still, beyond cancer, Lissa’s method shows that approved drugs could be screened for treating other diseases, reducing the cost of finding new treatments.

Originally published on The Conversation UK.

Lissaa, D., Senovillaa, L., Rello-Varona, S., Vitalee, I., Michauda, M., Pietrocola, F., Boilèvea, A., Obrist, F., Bordenave, C, Garcia, P., Michels, J., Jemaà, M., Kepp, O., Castedo, M., & Kroemer, G. (2014). Resveratrol and aspirin eliminate tetraploid cells for
anticancer chemoprevention PNAS DOI: 10.1073/pnas.1318440111

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Bright Night Lights: Tracking Light Pollution from Space

6483519343_0199a1c7f1_bThe creep and sprawl of artificial urban lighting is probably the most pervasive technological innovation of the 20th century. Keeping track of how artificial light is changing Europe’s nightscape is important, since more light is typically associated with greater economic development and urban expansion, but moderating light consumption helps to stabilise the ecosystem and energy security.

Scientists have recently used satellite night images going back as far as 1992 (publicly available from the Defense Meterological Satellite Program databank) to analyse how artificial light coverage across the European landscape has changed through the years.

light in europeOverall, light brightness across Europe increased over the years (shown above), with Liechtenstein showing the strongest surge. Conversely, certain countries showed substantial drops in brightness, most notably Slovakia. Small spots puckering the UK, Belgium, Denmark, Finland, Germany, Norway and Sweden also dimmed over time, and often corresponded with a loss of industrial manufacturing, the closure of military sites, the modernisation of lighting infrastructures or deliberate money-saving measures. In other areas, darkness coincided with a loss of economic stability, for example when Ukraine and Moldova became independent from the Soviet Union.

This extremely cool research shows that it’s possible to track changes in light brightness across the European night sky, giving us an excellent tool to help develop interventions that minimise the effects of light pollution and re-establish the ability to enjoy the sensational stars hanging over our heads.

Bennie J, Davies TW, Duffy JP, Inger R, & Gaston KJ (2014). Contrasting trends in light pollution across Europe based on satellite observed night time lights. Scientific reports, 4 PMID: 24445659

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Where in the body do our emotions lie?

lego emotions cc danielito311

Emotions are strange things, bursting over us as we react to life’s joys and challenges. While they might be thought of as ethereal entities with no fixed form or function, emotions actually produce very tangible physical reactions throughout the body.

These emotionally-driven physical reactions are important for surviving in the real world. For example, fear generates a helpful physical response that prepares your body to fight or flee. But we don’t really know if an emotion can fuel a reaction in a certain body part, or if regional body sensors can dictate our conscious emotional experiences.

A team of Finnish researchers were interested in finding out more about this, so they showed 701 volunteers an outline of the human body, and asked them to point out spots on that body where they felt a change in activity (either growing stronger or weaker) after they experienced an emotion generated by a certain word, story, film or facial expression.

They exposed the volunteers to six “basic” emotions (anger, fear, disgust, happiness, sadness and surprise) and seven “complex” emotions (anxiety, love, depression, contempt, pride, shame and envy), and tried their best to weed out the inherent bias of using emotive words that are culturally and lingustically associated with body parts, like “heartache”.

feeling emotions

After mapping out the results as emotional activity charts across the human body, they found that positive emotions like happiness, love and pride all looked very similar, with a suffusion of high activity (shown in yellow, above) around the heart, head, and, ahem, nether regions (for love). These associations were supported by some lovely quantitative cluster analysis.

Several of the negative emotions assembled into similar patterns: fear and anger increased activity in the chest, anxiety and shame increased activity in the torso, sadness and depression severely decreased activity in the arms and legs (shown in blue, above), while disgust, contempt and envy increased activity in the head and hands.

So, clearly, emotions can pin themselves quite reliably and reproducibly to certain areas of the human physical form, in a way that transcends cultural heritage (both Western European and Eastern Asian volunteers reacted in the same way). Such bodily associations and sensations likely have a key part in the emotional experience, and may have a core role in helping us to understand emotions in others.

Nummenmaa L, Glerean E, Hari R, & Hietanen JK (2013). Bodily maps of emotions. Proceedings of the National Academy of Sciences of the United States of America PMID: 24379370

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Antibiotics release death sugars that help bad bugs to grow

4619706028_7c9e124627_bIn the 1940’s, antibiotics were hailed as wonder drugs. “Syphilis is now curable!”, ran the posters. Yet in modern times, several dark sides of these drugs have come to light.

The widespread overuse of antibiotic therapy has driven the emergence of superstrong bacteria, like MRSA, that resist the activity of conventional antibiotics.

Antibiotic therapy is also troubled by the problematic core concept that it lacks specificity, and wipes out good and bad bugs alike. This is particularly worrying as we continue to discover just how much the trillions of good bugs that live in our gut contribute to our health and wellbeing, absorbing vitamins from our food, breaking down tough fibrous vegetables, working to prevent allergies and keeping bad bugs in check.

When good bugs are killed off by antibiotics, the gut ecosystem becomes remarkably disturbed. Large pools of sugary nutrients that the good bugs normally eat suddenly become available, forming an all-you-can-eat buffet for surviving bacteria. Unfortunately, the post-antibiotic apocalypse scavengers are often bad bugs, like Salmonella enterica and Clostridium difficile, which can cause unpleasant disease.

New research from Stanford University School of Medicine shows that both Salmonella enterica and Clostridium difficile use the same strategies to access these free pools of death sugars. Using genetic profiling, they found that in the wake of antibiotic therapy, the bad bugs increased their capacity to snack on fucose and/or sialic acid. Consequently, they were able to overgrow in the intestine to cause pooping nastiness.

While the community of good bugs began to be re-established around three days after antibiotic therapy, and the balance of good and bad bugs stabilised, eating probiotics packed with good bugs that are particularly adept at eating fucose and sialic acid during antibiotic therapy may prevent such pathogenic disturbances happening at all.

Ng KM, Ferreyra JA, Higginbottom SK, Lynch JB, Kashyap PC, Gopinath S, Naidu N, Choudhury B, Weimer BC, Monack DM, & Sonnenburg JL (2013). Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature, 502 (7469), 96-9 PMID: 23995682

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A Marvellous Month of Science

fungusFungal extracts prevent hepatitis C virus infection

Hepatitis C virus (HCV) is a huge cause of liver cancer, but current treatments are very expensive and not that great. Since HCV is a cunning little virus capable of quickly evolving drug resistance, simultaneously attacking it at several key points during its life cycle has the best chance of resolving infection. Researchers in Japan have now created and screened a library of 300 natural drugs isolated from fungi found on seaweed, mosses and other plants, and tested their ability to shut down HCV infection. One of their best hits, sulochrin, repelled several strains of hepatitis C virus, and was free from any toxic side effects. When they combined sulochrin with the traditional HCV drug, telaprevir, results were even better. Although any potential off-target effects of sulochrin still have to be ruled out, this research highlights that the natural world is a tremendously rich source of new drugs that should continue to be mined.

unwindingUnwinding shielded DNA attacks the root cause of prostate cancer

Most organs in the human body, including the prostate gland, contain a tiny population of stem cells that replace old defunct cells with shiny new ones. If these stem cells get damaged, they can become carcinogenic machines, dividing uncontrollably to form a tumour. Such cancer stem cells are thought to be the driving force that creates prostate tumours. Cancer stem cells are very difficult to kill, since they have excellent inbuilt safety features, one of which is very tightly coiled DNA that rebuffs normal treatments. Researchers at the University of York have now shown that treating prostate cancer stem cells with drugs that unwind and relax DNA sensitises them to common chemotherapies, allowing them to be destroyed and ultimately preventing tumour relapse.

Chilly temperatures help cancers to grow

7041602511_b7b65fc443_bAt low temperatures the human body has a hard time, entering a state of thermal stress  where only the most vital systems, like the brain, are left switched on. Now, a paper published in PNAS suggests that cold has yet another disadvantage – it changes the way cancer cells grow and spread, at least in mice. Mice living in a relatively cold environment (around 22°C) had cancers that grew more quickly and aggressively than mice living at a nice thermally comfortable temperature (around 30°C). Both the cold and the comfortable mice had the same numbers of potential cancer-fighting immune T cells when they were healthy, but when they got sick, the T cells in the comfortable mice were quicker and better at burrowing into the tumour to attack it. They also secreted more cancer-fighting substances than the cells from cold mice. In the tumours of cold mice, there were greater numbers of suppressive cells capable of shutting down normal immune responses. Cold temperatures, then, shifted the body’s response from fighting the tumour to accepting it. This suggests that the benefits of heat therapy for cancer may have been largely overlooked. Adapted from an article originally published on The Conversation.

HSVCommon chemotherapy drug helps oncolytic viruses kill tumours

There is a lot of excitement in the world of cancer immunotherapy over the potential utility of oncolytic viruses – that is, viruses that specifically infect and destroy cancer cells with the help of the immune system. Since a tumour is essentially a big chunk of overgrown tissue, the immune system often continues to see it as a normal part of the body (although sometimes, the sneaky tumour simply makes itself invisible to the immune system). Even after immune-activating oncolytic virus treatment, properly re-educating the immune system to see the tumour as a malignant intruder is a very difficult process. Researchers at McMaster Immunology Research Centre now show that administering an oncolytic virus together with a chemotherapy drug that triggers the immune system as it kills cancer cells finally allows the tumour to be recognised as a threat. Once that biological brake has been removed, cancer-fighting immune cells can pour into the tumour and secrete cancer-busting substances. Such exciting new combination therapies can help retrain the immune system to identify developing malignant disease.

Originally published on Scizzle.

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Chilly temperatures help cancers grow

7041602511_b7b65fc443_bAt low temperatures, the human body has a hard time. As the cold sets in, blood vessels constrict to maintain heat and some body parts – like fingers and toes – begin to suffer. Metabolism ramps up to fight the cold and shivering sets in. As these conditions continue, everything becomes sluggish as the cells of your body do not work as well. The body enters a state of thermal stress and only the most vital systems, like the brain, are left switched on.

Now, in a paper just published in the Proceedings of the National Academy of Sciences, Elizabeth Repasky at Roswell Park Cancer Institute in the US and colleagues suggest that cold has yet another disadvantage – it changes the way cancer cells grow and spread, at least in mice. This raises interesting questions about cancer therapies and many cancer studies, which tend to use mice as animal models.

Repasky found that mice living in a relatively cold environment (around 22°C) had cancers that grew more quickly and aggressively than mice living at a nice thermally comfortable temperature (around 30°C). A cold environment boosted the growth of several different types of cancer, including breast, skin, colon, and pancreas.

It did not matter if mice had lived in the cold for a lifetime before they got cancer—a chilly exposure even after their cancer had become established still made their tumours grow more quickly.

The body’s anti-cancer responses are mostly driven by the immune system’s T cells, which recognise and destroy tumor cells based on the altered proteins they produce. Tumours often react to a T-cell attack by producing signals that trick the body into suppressing these immune cells. This battle continues until one side outpaces the other – a lot of anti-cancer treatments given in the clinic help to swing the balance in favour of the immune system.

Both the cold and the comfortable mice had the same numbers of potential cancer-fighting T cells when they were healthy. But the tumour-seeking T cells in the comfortable mice were quicker and better at burrowing into the tumour to attack it. They also secreted more cancer-fighting substances than the cells from cold mice.

In the tumours of cold mice, there were greater numbers of suppressive cells capable of shutting down normal immune responses. Cold temperatures, then, shifted the body’s response from fighting the tumour to accepting it.

Most animal research facilities follow the same housing guidelines, and thus keep mice at colder-than-comfortable temperatures. This could introduce a systemic bias to animal testing where studies are done in conditions that aren’t entirely relevant. For example, what if you were trying a therapy that boosted immune function but did it in mice whose immune function was naturally tamped down? You might see no effect, when it could still be a useful drug. In contrast, something that causes tumour DNA damage might not have the same problem.

Cancers are cold

When we feel cold, we engage in warming behaviours – turning the thermostat up a notch, or thriftily putting on an extra layer of clothes. Mice are exactly the same – if they feel cold, they move to a warmer spot. When healthy mice get to choose what temperature they want to hang out at, with options at 22, 28, 30, 34 or 38°C, they typically migrate into the comfortable 30°C room. Mice with tumours tend to choose the hottest 38°C room. Cancer patients also commonly report suffering deep chills, especially following treatment.

It’s possible that growing tumours may induce a cold stress that probably promotes their own survival. We do not know exactly how this works yet, but this research still has important implications for cancer patients and their treatments. Could administering cancer therapies in a sauna – like setting improve their tumour – fighting potential and slow cancer growth?

Such approaches have been tried in small trials for breast cancer, angiosarcoma and sarcoma. They show that increasing body temperature to a mild fever over the course of a few hours improves response rates to radiation therapy.

Without large-scale studies no firm conclusions can be drawn, but this evidence suggests that the benefits of heat therapy for cancer may have been overlooked. Perhaps it is time we paid heed to the words of the ancient Greek physician Hippocrates:

Those who cannot be cured by medicine can be cured by surgery. Those who cannot be cured by surgery can be cured by heat. Those who cannot be cured by heat are to be considered incurable.

Originally published on The Conversation UK.

Kokolusa, KM, Capitanoa, ML, Leea, CT, Enga, JWL, Waighta, JD, Hylandera, BL, Sexton, S, Hong, CC, Gordon, CJ, Abrams, SI, & Repasky, EA (2013). Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature PNAS : 10.1073/pnas.1304291110

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Creepy crawly centipedes are a source of new high-strength painkillers

13161493I’m dreading the day I get knocked up, since I know that my incredibly low pain threshold will have trouble dealing with the crazy horror that is childbirth.

That’s why I was overjoyed to hear of some new research from Australia, where a new high-strength painkiller has been isolated from the venom of the Chinese red-headed centipede, Scolopendra subspinipes mutilans.

Scolopendra_subspinipes_mutilans_DSC_1438

In the insect world, centipedes are king of the hill – their venom is debilitating to their prey, helping them to capture fish, lizards, frogs and even small mammals.

Centipede venom is made up of a complex cocktail of proteins, each designed to disengage a particular biological pathway. Researchers isolated one of these proteins, µ-SLPTX-Ssm6a, and found that it blocked a specific pain receptor known as the voltage-gated sodium channel, Nav1.7.

For several types of chemical-, temperature- or acid-based pain, µ-SLPTX-Ssm6a provided better pain relief than the current gold standard, morphine. Happily, no side effects were observed.

So, µ-SLPTX-Ssm6a is a great new drug candidate for human pain relief. And since other beastie-derived venom proteins are already in clinical use – like PRIALT from the marine cone snail – µ-SLPTX-Ssm6a could make it to market before I find me a baby daddy.

Yang S, Xiao Y, Kang D, Liu J, Li Y, Undheim EA, Klint JK, Rong M, Lai R, & King GF (2013). Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models. Proceedings of the National Academy of Sciences of the United States of America, 110 (43), 17534-9 PMID: 24082113

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Pumping out Petrol with Bioengineered Bugs

petrol

One of the terribly tricky questions in this ol’ world of ours is how to sustain a species that likes to extract toxic crude oil from the ground and use it in a way that’s disturbingly damaging to the environment they live in.

But imagine how much closer we would be to a renewable energy revolution if instead of sucking fossil fuel out of the earth, there was an alternative way to satisfy our need for fuel.

Enter: microbes.

We’ve already created genetically engineered bacteria that produce diesel, but not our favourite fuel, petrol. The difficulty lies in convincing bacteria to produce the short-chain hydrocarbons that form part of the petrol cocktail, since they much prefer making longer chains.

Researchers in South Korea have now addressed this issue by creating two new strains of Escherichia coli bacteria. After engineering in lots of additional genetic hardware – including DNA from Clostridium, Arabidopsis and Acinetobacter species – they substantially bumped E.coli’s capacity to produce short-chain hydrocarbons.

The first strain, Gas-2, produces a steady stream of short-chain free fatty acids, which are intermediate products in the petrol creation process, while the second strain, Gas-3, churns out short-chain hydrocarbons (i.e. petrol) at a rate of 580 milligrams per litre.

This work represents an excellent new starter platform for the sustainable production of biofuels.

Choi YJ, & Lee SY (2013). Microbial production of short-chain alkanes. Nature, 502 (7472), 571-4 PMID: 24077097

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“Grape-like aromas” keep mosquitoes at bay

mosquito_terror_by_kittenmittenmuffin-d5bgh44The mosquito is my dad’s nemesis in the insect world. He will go to extraordinary lengths to secure his person from mosquito attack, roaming the corridors on night patrols and jamming mosquito repellent devices into every possible plug socket.

Such devices are usually based on the chemical, N, N-diethyl-meta-toluamide, or DEET. The problem with DEET is it’s expensive, it has nasty effects on our own skin and mosquitos are evolving resistance to it.

But replacing DEET has proven a tricky business, since we don’t really know exactly how it prevents mosquitoes zeroing in on their bloodbag human targets.

Until now.

A team of researchers from the University of California found that mosquito nerve cells in the antenna expressing the receptor Ir40a were crucial for the anti-DEET effect. When this receptor was blocked, mosquitoes became resistant to DEET – and in a nightmarish twist, some became more drawn to its scent.

They then used a computer algorithm to screen over 3000 “natural odours”, including extracts from plants, insects or vertebrates, and ones already approved for use in perfumes, cosmetics and food additives, for their predicted ability to block Ir40a receptors.

Three promising compounds with a “grape-like aroma”, plus a fourth that ants secrete to mark their trail, had strong effects on nerves expressing Ir40a and repelled mosquitos.

Since these compounds already have WHO and FDA approval, they are exciting new candidates for an improved class of bug repellents that could be speedily translated to market.

Kain, P, Boyle, SM, Tharadra, SK, Guda, T, Pham, C, Dahanukar, A, & Ray, A (2013). Odour receptors and neurons for DEET and new insect repellents Nature : 24089210

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How to: boost resistance to tuberculosis

Mycobacterium tuberculosis

Most kiddies receive the very effective Bacille Calmette-Guérin (BCG) vaccine against tuberculosis during childhood, but as they grow up, the protection afforded by this vaccine wanes.

Since cases of adult TB are on the rise, receiving an immune upgrade would be a great benefit to boost immune protection.

One team of researchers at McMaster University, led by Professor Zhou Xing, have now developed a new booster vaccine based on adenovirus, which causes the common cold.

In 26 healthy adults, they showed that this vaccine could generate robust immune responses against TB. Anti-TB immune cells created by the booster vaccine performed better in people that had previously received the childhood BCG vaccine, secreting a wider range of protective immune factors.

Since this novel booster vaccine has proven safe and very effective at reawakening TB immunity in BCG-vaccinated healthy adults, it will now move on to the next stages of clinical trials.

Smaill F, Jeyanathan M, Smiejal M, Medinal MF, Thanthrige-Don N, Zganiacz A, Yin C, Heriazon A, Damjanovic D, Puril L, Hamidl J, Xie F, Foley R, Bramson J, Gauldie J, & Xing Z (2013). A Human Type 5 Adenovirus–Based Tuberculosis Vaccine Induces Robust T Cell Responses in Humans Despite Preexisting Anti-Adenovirus Immunity Science Translational Medicine, 5 (205) DOI: 10.1126/scitranslmed.3006843

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A Marvellous Month of Infectious Science

Cold weather helps to spread flu across the country

snowA very cool new study from McMaster University researchers shows how weather patterns impact the spread of influenza A virus across Canada. Using outbreak data gathered over more than 13 years, the virus could be tracked over time and space. Influenza A tended to first emerge in the colder, less humid provinces of Western Canada (British Columbia and Alberta), and then spread across the country to the East. Schools also represented hotbeds of infection – when they were shut during the Summer, there were significantly fewer cases of flu recorded.

Investigating the ‘ouch’ factor during a bacterial infection

nerveWhen a bacterial infection takes hold, it’s usually a painful experience. During a normal immune response, immune cells infiltrate the infected area, pummel the invading bacteria and in doing so release molecules that cause swelling and pain. Yet new research from Harvard Medical School shows that it’s not only the immune system that is to blame: at least some of the pain comes from the bacteria themselves secreting factors that can interact directly with our nervous system.

The immune system’s need for speed

speedOur beautiful human bodies have several portals where nasty pathogens, such as bacteria, can enter and wreak havoc. Once inside the human body, bacteria start reproducing straight away, doubling their numbers around once every 20 minutes. Yet our immune T cells constantly patrol such vulnerable open-access areas, sampling their environment to identify threatening material. A reassuring new study has now come out showing that reactive T cells sense such foreign material within a few seconds, and make the decision to respond to malevolent threats within a speedy minute.

Edible vaccines, om nom nom!

OLYMPUS DIGITAL CAMERARotavirus infection is one of the major nasty causes of childhood diahorrea, but can happily be prevented with an oral vaccine. Vaccinated children in industrialised countries develop 85-98% immune protection, while those in the third world develop a much lower protection level of 50-60%. The reasons behind this startling difference are not well characterised, but third world kiddies would obviously benefit from a boost in their rotavirus immune protection.

One team has come up with a new way of administering such an immune upgrade – by loading rice, a staple food in the third world, with anti-rotavirus immune-boosting antibodies. This tasty dish could conceivably be consumed regularly during childhood to maintain protection levels.

Originally posted on Scizzle.

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The fairly depressing picture of pesticide pollution in British rivers

2405003862_2c3ece1e79_bLots of pesticides – such as the organochlorine insecticide, DDT – that were widely used in the fairly recent past are now banned after having serious effects on the health of humans and other species.

Yet old and new pollution of rivers and streams is still an issue across Europe, since waste water treatment practises don’t remove potentially harmful substances like pesticides, toxins, synthetic hormones and pharmaceutical drugs.

One team of researchers wanted to assess the levels of contaminants and the state of river recovery across 33 rivers in South Wales, UK, that were badly polluted in the past. To do this, they sampled toxin levels in the eggs of the Eurasian dipper (Cinclus cinclus), a waterbird that is well known to act as a pollution bioindicator.

cinclus_cinclus_2332They found that eggs from urban areas contained higher levels of modern pollutants, like toxic PCBs and PBDEs, while eggs from rural areas had higher levels of old agricultural pollutants, such as the pesticides DDE (a breakdown product of DDT) and dieldrin.

When the team compared current pesticide levels with those recorded 20 years ago, there was little or no reduction, and the concentrations of some pesticides – such as HCB and lindane –  had actually increased to levels high enough to affect bird development.

This research indicates that British water wildlife is not being properly protected by current legislation governing levels of toxic substances in rivers, and a new approach to water security is badly needed.

Paper: http://goo.gl/OZ6Dtj

Morrissey CA, Stanton DW, Pereira MG, Newton J, Durance I, Tyler CR, & Ormerod SJ (2013). Eurasian dipper eggs indicate elevated organohalogenated contaminants in urban rivers. Environmental science & technology, 47 (15), 8931-9 PMID: 23819781

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Magnificently Mathematical Mussels

2898357773_22f8feafb3_bDespite the ease with which mussels can be cooked and eaten with chips, harvesting these tiny shelled bivalves from the seashore requires a certain amount of industrious prising.

That’s because mussels use multiple thin byssus threads to securely fasten themselves to different surfaces along the coastline. These threads have a sticky plug at one end, with the mussel’s body dangling off the other (shown below).

musselScientists have found it difficult to explain how mussels tolerate the forces generated by constantly crashing waves and strong sea currents, since the calculated strength of the byssus threads alone is too low to withstand them.

So, how exactly do mussels manage to stay attached to a rocky coastline, or the hull of a fast-moving ship?

Researchers at MIT explored this question by collecting mussels from Boston harbour, and testing them under different conditions.

They found that byssus threads are not made up of the same material all the way through. Instead, the thread sports a mixture of soft and hard material that optimises its ability to resist impact forces.

The soft material nearer to the body of the mussel deforms as mechanical forces are applied, while the hard material closer to the sticky plug stays in a very relaxed state until substantial force is applied.

This geometric structure results in a 900% increase in the mussel’s ability to withstand repeated bashing by waves (dynamic strength) compared to its ability to resist constant pressure (static strength).

This arrangement also conspires to create the least amount of force at the junction between the mussel’s body and the byssus thread, minimising the likelihood of a horribly wrenching separation.

Other animals using this ingenious materials design include the mantis shrimp and certain ancient fish.

This research has wonderful implications for the bio-design of new materials that need to withstand significant push/pull forces, such as submarines, wind turbines and materials going into space.

Qin Z, & Buehler MJ (2013). Impact tolerance in mussel thread networks by heterogeneous material distribution. Nature communications, 4 PMID: 23880603

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Particle accelerators: making life better since 1932

(cc) dvarg

(cc) dvarg

Atoms form the building blocks of everything that exists in the world, holding chairs, rocks, water and our bodies together in strong, stable structures.

But atoms themselves are made up of lots of composite parts, called sub-atomic particles. Such particles exist in high energy states, and we can find out much more about them using huge particle accelerators, like the Large Hadron Collider. In these machines, atoms are smashed together to leave behind a big pile of sub-atomic debris. This can be sifted through to identify the pieces that are left behind, and to find out exactly how atoms stick so tightly together.

Although it’s fun to hammer atoms together at close to the speed of light, learning more about the structure of matter also impacts our everyday lives. High energy particles are used in electronics, medicine, environmental clean ups and energy production, and exciting new particle accelerator discoveries can be expected to supply a steady stream of future advancements.

Particle accelerators improve medical treatments

High energy particle beams created by miniaturised particle accelerators are currently used in several cancer clinics to shrink tumours. These beams deliver an incredibly precise dose of radiation to cancerous tissue, and come with fewer side effects than traditional therapies. Fourteen centres across Europe currently offer particle accelerator cancer treatments.

Particle accelerators make chocolate smoother

chocolate

Particle accelerators can unravel the molecular structures of different objects. For food scientists, the edible structures of tasty treats can be analysed to discover how different recipes produce the best flavours. For example, particle accelerator experiments have shown that fat-free chocolate CAN be tasty, depending on its atomic structure. Reducing the fat content typically leads to issues that scientists refer to as “poor in-mouth melting properties“. Chocolate recipes made with varying proportions of fats produce bars with different sub-atomic structures, some of which always go down smooth.

Particle accelerators help to clean up the planet

Toxic sludge can spill into the water, land and air, and cleaning it up is a chemically complicated problem. Analysing contaminated samples in a particle accelerator can tell us the exact blend of dirty elements present, what state they exist in and the best ways to purge them from the environment. Such analyses helped to clean up large spills of heavy metals in Hungary after tanks storing contaminated red mud excavated during mining operations accidentally failed.

Allison RR, Sibata C, & Patel R (2013). Future radiation therapy: photons, protons and particles. Future oncology (London, England), 9 (4), 493-504 PMID: 23560373

Do TA, Hargreaves JM, Wolf B, Hort J, & Mitchell JR (2007). Impact of particle size distribution on rheological and textural properties of chocolate models with reduced fat content. Journal of food science, 72 (9) PMID: 18034724

Burke IT, Mayes WM, Peacock CL, Brown AP, Jarvis AP, & Gruiz K (2012). Speciation of arsenic, chromium, and vanadium in red mud samples from the Ajka spill site, Hungary. Environmental science & technology, 46 (6), 3085-92 PMID: 22324637

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A Marvellous Month of Science

Taking vitamin supplements might not be as healthy as you think

vitaminsAntioxidant vitamins, like vitamin C and E, are thought to boost health by reducing the creation of DNA-damaging free radicals that can contribute to the ageing process. In lab mice, there is some suggestion that vitamin supplements can extend lifespan, but since laboratory-bred mice are genetic clones, such studies may bear little relevance to a hugely genetically diverse human population.

Giving wild animals, such as the short-tailed field vole, either vitamin C or E supplements has now been shown to have a less positive impact on health. Animals taking either vitamin had a decreased lifespan compared to their non-vitamin chowing counterparts. This aligns with a Cochrane analysis that suggests the same thing happens in humans.

How does the naked mole rat stay cancer-free?

Naked Mole-ratThe naked mole rat is an object of scientific fascination, not just for rocking a quirky look but also for its biological anomalies. In the world of small mammals, it has a remarkably long lifespan (more than 30 years), paired with a complete inability to develop cancer.

Now, a team of researchers led by Xian Tian have shown that the fibroblasts of the naked mole rat, which act as nurturing cells that provide structural and chemical support to other specialised cells, secrete a wonderful version of hyaluronan to produce this anti-cancer effect. Hyaluronan forms part of the extracellular matrix that sticks cells together in a nice ordered pattern. It builds up in naked mole rat cells to protect them by dampening cellular proliferation and inflammation. Removing hyaluronan from these cells renders them sensitive to malignant transformation. Using hyaluronan in the clinic may prove useful for preventing cancer and extending lifespan.

Presenting: the first ultrahigh resolution atlas of the human brain!

Image converted using ifftoanyThe human brain is a fascinating organ that shapes, defines and controls us as individuals. Yet its structure remains frustratingly complex to dissect, and we are only just beginning to understand the anatomical features that can easily be seen by the naked eye. Analysing fine ultrastructural details, including how more than 170 billion neural cells are connected, has proven a tricky task.

To address this issue, a single human brain donated by a 65 year old woman was cut into 7,400 thin slivers, which were stained, photographed and painstakingly fitted back together to create the first high definition 3-D reference map of the human brain. Lovingly known as, “BigBrain”, this new publicly available biological encyclopedia should help us better understand the nature of language, emotions and consciousness.

You can watch a video of the 3-D BigBrain map here: http://youtu.be/nJpFvQ0YZLk

Visit the database here: https://bigbrain.loris.ca/main.php

Stem cells work in shifts to replenish immune patrols in the blood

4. Hemo-StemB and T cells are lethal immune warriors that circulate in the blood and vanquish pathogenic invaders. Yet they don’t live forever, and have to be periodically replenished to maintain immune protection. The sources of this renewal are the haematopoietic stem cells (hSCs) that reside in the bone marrow, where they proliferate to generate their warrior progeny.

A team of researchers from The Netherlands looked at how many fresh B or T cells each individual haematopoietic stem cell added to the total immune cell pool. They found that the contribution of each hSC expanded and declined at different times. When one stem cell was churning out a large number of progeny, the others rested before taking their turn later on. Each stem cell also appeared to be dedicated to producing either B or T cells, and wasn’t able to swap between the two.

Originally posted at Scizzle Blogs

Selman, C., McLaren, J.S., Collins, A.R., Duthie, G.G., & Speakman, J.R. (2013). Deleterious consequences of antioxidant supplementation on lifespan in a wild-derived mammal Biology Letters, 9 (4) DOI: 10.1098/rsbl.2013.0432

Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M, Ablaeva J, Mao Z, Nevo E, Gorbunova V, & Seluanov A (2013). High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature, 499 (7458), 346-9 PMID: 23783513

Amunts K, Lepage C, Borgeat L, Mohlberg H, Dickscheid T, Rousseau MÉ, Bludau S, Bazin PL, Lewis LB, Oros-Peusquens AM, Shah NJ, Lippert T, Zilles K, & Evans AC (2013). BigBrain: an ultrahigh-resolution 3D human brain model. Science (New York, N.Y.), 340 (6139), 1472-5 PMID: 23788795

Verovskaya, E., Broekhuis, M.J.C., Zwart, E., Ritsema, M., van Os, R., de Haan, G., & Bystrykh, L.V. (2013). Heterogeneity of young and aged murine hematopoietic stem cells revealed by quantitative clonal analysis using cellular barcoding Blood, 122 (4), 523-532 DOI: 10.1182/blood-2013-01-481135

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Clouds of decoy viruses help cure genetic disease

Helpful viruses get protected by decoy viruses in the bloodstream. Maddy Cow.

Helpful viruses get protected by decoy viruses in the bloodstream. Maddy Cow.

The presence of foreign objects, like viruses, in our bloodstream is usually a bad thing. Evolution has created some extremely efficient immune cells that patrol the blood, seeking out material that should not be there, and shutting it down.

Sometimes, though, viruses circulate in the blood for beneficial purposes. Gene therapies often deliver viruses as couriers to deliver new DNA to repair faulty cells. Getting viruses into the bloodstream is simple, but keeping them “active” during their time inside the body is difficult. This is particularly true if the immune system has encountered them before. Even though therapeutic viruses are engineered to be beneficial, the immune system doesn’t recognise the difference, and starts a defensive response.

Now a team led by Federico Mingozzi at the Children’s Hospital of Philadelphia has come up with a way of preventing such therapeutic viruses from being decommissioned by the immune system, by hiding the virus particles inside a cloud of decoy empty virus particles.

As they report today in the journal Science Translational Medicine, the team developed an engineered version of adeno-associated virus (AAV) as a genetic courier for the treatment of haemophilia B. This disease stems from a mutation in the DNA of liver cells that prevents them from producing normal levels of an enzyme called coagulation factor IX. Such patients can bleed to death without proper treatment.

Mingozzi’s AAV was designed to deliver a DNA payload to the liver. This DNA contained instructions to produce the correct version of coagulation factor IX, a crucial protein involved in blood clotting, in the hope that it would cure this genetic disease.

Stealth tactics

Viruses consist of two parts: a genetic core (either DNA or RNA) and a protective protein shell. When a virus infects a human, the host immune system typically triggers a cascade of defensive reactions. One of the most effective responses is the production of neutralising antibodies that recognise and attach to the virus shell and squelch its activity.

Mingozzi’s choice of AAV as a genetic courier would seem counter-productive then, since between 30% to 60% of the human population has previously been exposed to AAV. Thus, their immune systems have learned to recognise AAV shells. In such immune individuals, even though the engineered version of AAV contains beneficial genetic information, it gets quickly tagged for destruction and obliterated long before it reaches its target destination (the liver).

Even when a large number of AAV particles are administered to improve the odds of some getting through, the immune system mops them up. The few particles that do survive the journey initiate the production of normal coagulation factor IX in liver cells, but only manage to reconstitute around 10% of the normal volume of the coagulation factor IX pool.

So Mingozzi came up with an idea to fool the immune system. He mixed therapeutic AAV particles containing the right genetic information with lots of empty AAV shells lacking a DNA core, and injected them into mice (used as a proxy for humans). This created a smokescreen, allowing the therapeutic AAV particles to dodge the immune system’s attack.

This new approach enhanced AAV survival in the bloodstream of mice. Depending on how immune each individual mouse was to AAV, a personalised ratio of empty AAV particles to real AAV particles was administered. Mice with higher levels of AAV antibodies received more empty decoy shells.

Circulating AAV antibodies, which exist in immune individuals, attacked both empty and active versions of AAV, but enough active virus got to the liver to boost coagulation levels beyond those seen in an average mouse. These beneficial effects lasted up to four weeks – an excellent timeframe given that a severely affected haemophilia B patient has to inject themselves every day.

They also tested out the same idea using animals more closely related to humans – rhesus macaques – where the presence of decoy virus gave real AAV particles the same survival extension, and boosted coagulation factor IX levels to a similar degree.

Importantly, when different monkey tissues were examined after administering empty and real AAV formulations, all the activity predominantly happened in the liver, with no unsafe, off-target effects in other organs.

Perfecting the decoy trap

The first generation of decoy viruses used in this study were designed to be exact replicas of AAV, but without the DNA payload. Unfortunately, these decoy viruses behaved too much like the real thing, attaching to target liver cells and by virtue of their overwhelming numbers, out-competing the binding of real, therapeutically-relevant virus. Once inside liver cells, bits of these empty viruses then presented enticing foreign targets to the immune system.

Tweaking the design of the empty virus shell in the second generation of decoy viruses prevented it from binding liver cells, boosted the binding of real virus and replicated the rise in coagulation factor IX levels. It also had the happy consequence of dampening certain sections of the immune response.

Using fake viruses as bodyguards is an ingenious way of protecting therapeutic viruses in the bloodstream. This approach could represent the start of a therapeutic revolution for haemophilia B patients, and others with genetic diseases.

(Originally posted on The Conversation).

Mingozzi, F., Anguela, X.M., Pavani, G., Chen, Y., Davidson, R.J., Hui, D.J., Yazicioglu, M., Elkouby, L., Hinderer, C.J., Faella, A., Howard, C., Tai, A., Podsakoff, G.M., Zhou, S., Basner-Tschakarjan, E., Fraser Wright, J., & High, K.A. (2013). Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys Science Translational Medicine, 5 (194)

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Gene therapy using stem cells prevents inherited diseases

Originally written for The Conversation.

Gene therapy: not just for mice. J. Bradbury.

Gene therapy: not just for mice. J. Bradbury.

Genetic traits like a bulbous nose or balding give some people reasons to moan about what they inherited from their parents. But more serious genetic flaws can cause debilitating disease. Now, Italian researchers have come up with a way of treating one such inherited disease and reversing another using a promising new method of gene therapy.

The idea behind gene therapy is to replace a faulty gene with a shiny new version that works properly. Modified versions of viruses, which have been sculpted by millions of years of evolution, perfectly penetrate human cells. They act as couriers delivering DNA payloads to defective cells and ensure it is stably inherited.

This deceptively simple idea, though, has been challenging to achieve in practice. The first commercial gene therapy product, Glybera, only received regulatory approval in 2012.

Part of the reason for this is the difficulty of successfully clearing three hurdles at once: delivering replacement genetic information to the exact cells that need help, getting this information safely translated in high enough volumes to overcome the defects and stopping the immune system from reacting to “normal” genes when it has grown used to only seeing mangled ones.

Now, a team led by Alessandra Biffi at the San Raffaele Scientific Institute in Milan, Italy reports in the journal Science that they have developed a new approach that navigates each of these hurdles to treat three children with metachromatic leukodystrophy (MLD), a devastating inherited disease that affects around 1 in 40,000 people.

Engineered stem cells

MLD usually manifests in early childhood and kills patients just a few years after the first symptoms appear. It is caused by a defect in a single gene, ARSA. This gene encodes information used by the lysosome, a piece of recycling machinery used by human cells to break down unwanted material. When this recycling process does not work properly in nerve cells, as is the case with MLD patients, they become filled with rubbish and begin to slowly decline, leading to brain and spinal cord degeneration, as well as sensory deprivation.

Defects in a single gene knock out lysosomal activity in nerve cells of the central and peripheral nervous system in metachromatic leukodystrophy patients. Peter Brophy, Wellcome Images.

Defects in a single gene knock out lysosomal activity in nerve cells of the central and peripheral nervous system in metachromatic leukodystrophy patients. Peter Brophy, Wellcome Images.

Supplying a replacement ARSA gene to affected cells in the nervous system is a tricky task, because these areas are heavily protected. To overcome these defences, the team employed haematopoietic stem cells (HSCs), which can usually be found nestling quietly in the bone marrow, as stealthy genetic couriers. A tiny number of these cells were harvested from each patient, loaded with benign viruses carrying a working copy of ARSA and put back into the bloodstream.

These engineered cells either lodged in the bone marrow or continued to travel around the body in the blood, where they corrected defective cells in the nervous system by supplying the normal version of ARSA. Because these were stem cells, they also reproduced to form new blood cells that themselves took on the same supportive roles.

Resurrecting lysosomes from the dead

Most MLD patients produce a garbled version of ARSA that has a very low level of activity, nowhere near enough to let the lysosome carry out its normal job. Restoring partial activity is not enough to make a clinical impact – levels must be hiked to make an obvious difference.

One way of maximising activity is to pack defective cells with lots of normal copies of the same genetic message. In this case, haematopoietic stem cell couriers were loaded with two to four copies of the same virus, introducing multiple reproductions of the normal ARSA gene into the host cell genome.

To check that these viral inserts did not cause any unintended biological disruptions, which could lead to very serious side effects (like leukaemia), every individual founder cell infused into the patients was tracked using a genetic barcode. While some original cells generated large pools of daughter cells early on, which could be a sign of dangerously uncontrolled growth, none of them continued to dominate the blood cell pool as time went by.

In the patients, levels of ARSA quickly skyrocketed to above-average concentrations in both the original courier stem cells and their progeny. More than a year after treatment, normal ARSA levels were detected in the cerebrospinal fluid of all three patients, a clear sign that the central nervous system had stabilised. All these kids, who have older siblings badly affected by the same disease, can now think, run, jump, sit, crawl, kneel, jump, roll and speak like similarly aged average preschoolers.

Using the same technique, in a separate paper in Science, a team led by Alessandro Aiuti of the same institute in Italy showed reversal of the Wiskott-Aldrich syndrome (WAS) in three other young patients.

Like MLD, WAS is also a disease caused by a defect in a single gene. The disease causes immune system dysfunction that leaves kids at high risk of infections, bleeding and being harmed by their own immune system. But HSCs loaded with viruses containing the correct version of the faulty gene were able to restore a properly functioning immune system.

Using this stem cell-based gene therapy technique, both these new studies have either prevented the onset of a serious neurodegenerative disease, or reversed existing immunological disease. These are a testament to the tremendous potential of gene therapy and they represent a great step towards long-lasting cures for single-gene diseases.

Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, Baldoli C, Martino S, Calabria A, Canale S, Benedicenti F, Vallanti G, Biasco L, Leo S, Kabbara N, Zanetti G, Rizzo WB, Mehta NA, Cicalese MP, Casiraghi M, Boelens JJ, Del Carro U, Dow DJ, Schmidt M, Assanelli A, Neduva V, Di Serio C, Stupka E, Gardner J, von Kalle C, Bordignon C, Ciceri F, Rovelli A, Roncarolo MG, Aiuti A, Sessa M, & Naldini L (2013). Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy. Science (New York, N.Y.) PMID: 23845948

Aiuti A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C, Dionisio F, Calabria A, Giannelli S, Castiello MC, Bosticardo M, Evangelio C, Assanelli A, Casiraghi M, Di Nunzio S, Callegaro L, Benati C, Rizzardi P, Pellin D, Di Serio C, Schmidt M, Von Kalle C, Gardner J, Mehta N, Neduva V, Dow DJ, Galy A, Miniero R, Finocchi A, Metin A, Banerjee P, Orange J, Galimberti S, Valsecchi MG, Biffi A, Montini E, Villa A, Ciceri F, Roncarolo MG, & Naldini L (2013). Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome. Science (New York, N.Y.) PMID: 23845947

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MESSENGER spacecraft helps uncover Mercury’s pummelled past

mercuryIn our solar system, Mercury is the teeniest planet, and nestles closest to the sun. Understanding how Mercury developed as the solar system formed is an intriguing question for space science, and a surprising amount of information can be uncovered by analysing the topographical atlas of Mercury’s surface.

The Mariner 10 spacecraft, which launched in 1973, sent back photographs of just under half of Mercury’s surface. Now, American researchers have used images from the glossy, ultramodern MESSENGER spacecraft (launched in 2004) that visualise the entire surface to identify new landscape features that might help to explain more about Mercury’s history.

They found that the oldest areas of Mercury were pockmarked with huge craters (10 – 1,000 km wide) that hail from an intense period of history around 4 billion years ago known as the Late Heavy Bombardment. This was a time when huge fields of asteroids and comets travelled through space and cannoned into different planets of our solar system, including Mercury and the moon (interestingly, Earth doesn’t show much evidence from this period since active tectonic plates and erosion constantly resculpt the planet’s surface).

Then, around 3.8 billion years ago, several areas of Mercury’s terrain appear to have been smoothed out by intense volcanic activity extending across the planet, erasing evidence of past craters. Since such smoothened areas mostly peter out towards the end of the Late Heavy Bombardment period, these volcanoes were likely activated by the constant impact of asteroids and comets.

Paper: http://goo.gl/PoHep

Marchi S, Chapman CR, Fassett CI, Head JW, Bottke WF, & Strom RG (2013). Global resurfacing of Mercury 4.0-4.1 billion years ago by heavy bombardment and volcanism. Nature, 499 (7456), 59-61 PMID: 23823793

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