Key B cell lymphoma gene identified

 

The first step to finding a new treatment for cancer is to identify pivotal factors, such as genes, that the disease cannot survive without. For the majority of B cell lymphomas, Dr Melnick and colleagues in New York have discovered one such gene: EZH2.

EZH2 is a master gene regulator used by B cells- the immune cells in charge of making antibodies. Master regulators like EZH2 simultaneously switch many genes on or off, and by doing so they coordinate the actions of multiple genes to achieve a common function. In the case of EZH2, this is the promotion of the division of B cells.

In normal B cells, EZH2 is only active during an immune response against invading foreign microbes, where many fully-fledged antibody producing B cells are needed.

Master regulators like EZH2 simultaneously switch many genes on or off

However, this ability of EZH2 to drive division also means that it is utilized by the majority of lymphoma cells to promote their accelerated division.  In addition, EZH2 often cooperates with another gene, the survival-promoting BCL2, to enable lymphomas to thrive further.

As the majority of B cell lymphomas depend on these genes for the vital functions of growth and survival, blocking the activity of both genes simultaneously will cripple the disease on both fronts.

This combined approach therefore constitutes a potentially powerful treatment. Accordingly, the EZH2 and BCL2 inhibitors had a much stronger effect when applied together than individually in tests on cells and mouse models. This research has provided a strong foundation for the further development of this therapeutic approach against B cell lymphomas.

DOI: 10.1016/j.ccr.2013.04.011

Written by Betty Lau.

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Extensive glacial retreat in the Mount Everest region

 

Researchers from the University of Milan have found that glaciers in the Mount Everest region are shrinking. Glaciers are large thickened ice masses made up from fallen snow after many years. Glaciers retreat or advance periodically, and these movements are usually very slow and only evident after a long period of time. However, retreat of glaciers can occur rapidly over a few months or years.

The glacier in this region has shrunk by 13% in the last 50 years

A study led by PhD student Sudeep Thakuri integrates satellite images and topographic maps to reconstruct the glacial history and analyse the extent of glacial change in the Sagarmatha National Park. They found that the glacier in this region has shrunk by 13% in the last 50 years, and the snowline shifted upward by 180 meters. The team has yet to establish what the causes of this phenomenon are, but they suspect it is caused by human-generated greenhouse gases which alter global climate.

The Himalayan glaciers and ice caps are a source of water supply and storage for Asia. Downstream populations depend on melt water for agriculture, power production and drinking, Thakuri reports. With future research the team plans to understand the behaviour of the hydrological cycle to predict future water availability in the region.

Written by Ornela De Gasperin Quintero.

 

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Cell body clocks are altered in depression

 

Our biological rhythms are tuned to the day-night cycles, light-dark cycles in which we live because the cells of our body have an in-built timekeeping capacity. Each cell has an internal clock, driven by the cyclic expression of certain genes, which in turn is kept in time by a master clock in the brain. A group led by Jun Li in the University of Michigan Medical School has recently found that this internal clock has fallen out of sync with the solar day in patients with depression.

Patterns of gene expression were disrupted in people with depression

The team, who published their results in the Proceedings of the National Academy of Sciences, analysed the patterns of gene expression in six regions of the brain from 55 individuals who did not suffer depression and 34 patients who did.

The team analysed the genes that were active at the time of death of the non-depressed individuals and looked at those whose activity varied throughout the day.  They found that people who died at a similar time of day had very similar patterns of gene expression, whereas people who died at opposite times of the day had very different ones. Their statistical analysis was so powerful that the pattern of gene expression could predict the time of death of those individuals for which it was not known.

This was not the case for people who did suffer depression: the cyclic patterns in gene expression seen in the controls were disrupted, and more importantly, they found a shift in timing in comparison to the controls. Importantly, this disruption could not be attributed to patients’s medication.

These findings now raise the challenge of identifying why the internal clock is disrupted in patients with depression.

DOI: 10.1073/pnas.1305814110

Written by Ana I. Leal Cervantes.

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Issue 27: Weird and Wonderful

A selection of the wackiest research in the world of science

Catch That Thought

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Mind reading has just become easier—at least where fish are concerned. In January this year, Akira Muto and colleagues published techniques for visualising neuronal impulses in the brains of zebrafish larvae, which effectively allowed them to track the fishes’ ‘thoughts’ in real time. To do this, they first developed a fluorescent probe sensitive enough to detect the activity of single neurons. They then engineered zebrafish that produce this probe in the visual processing area of their brains. Finally, they presented the fish with a free-swimming Paramecium, a tasty morsel by zebrafish standards, and watched the fluorescent signal dart through the fishes’ brains as they stalked their lunch. Zebrafish larvae are transparent, so the signal was easily visible; indeed, the Paramecium’s path precisely mirrored the pattern of neurons lighting up. One application of this novel technology is the high-resolution mapping of functional neuronal circuits. Since zebrafish and mammalian brains share the same basic organisation, these methods could also be used to screen new psychiatric medications: just add drugs to the fishes’ water and watch the resulting light show. Food for thought indeed. Joy Thompson

 

Could We Get Another Report, Please?

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The United States Secretary of Defence recently gave a speech outlining plans to reduce expenditure by cutting down on the number of costly reports undertaken by the Department of Defence (DOD). In response, the DOD prepared a report to provide guidelines for estimating the costs required for reports to be prepared. Naturally, this report about DOD reports had to be evaluated by the Government Accountability Office (GAO), for which they prepared a report entitled “Defense Management: Actions Needed to Evaluate the Impact of Efforts to Estimate Costs of Reports and Studies”. In their report, they praised the DOD for its report about reports, but recommended a few changes. In particular, the GAO reported that the DOD should evaluate and report on the effectiveness of its report about reports. In the long run, it is hoped that the GAO’s recommendation in its report about a report about reports for a report about the report about reports will cut down on the number of reports. For their efforts, the GAO won the 2012 Ig Nobel Literature Prize (http://www.improbable.com/ig/), but sadly did not show up to receive their award. Jordan Ramsey

 

Practising Alchemy Before It Was Cool

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For humans, alchemy might be a lost art; but in some bacteria, making solid gold from the mundane is simply part of their survival plan. Like many heavy metals, dissolved gold is toxic to life. The bacteria Cupriavidus metallidurans have been shown to swallow up dissolved gold from the environment. They then turn it into solid gold nanoparticles, which are non-toxic and can be stored inside the cells. Recently, a team from McMaster University found that Delftia acidovorans, a bacterium often found alongside C. metallidurans, takes a different approach. Instead of uptaking gold, it produces a novel protein called delftibactin to do the ‘dirty work’. Delftibactin, the alchemist’s secret weapon, turns dissolved gold into solid particles. Thus, toxic gold can no longer enter the bacterial cell and harm the alchemist itself. Last year Adam Brown, Associate Professor from Michigan State University, created the award- winning artwork The Great Work of the Metal Lover, bringing modern microbiological gold-digging to the historical context of ancient alchemy. While we may not see bacteria-run alchemical factories in the near future, researchers suggest delftibactin may be used to accelerate industrial chemical reactions or treat waste waters from mines. Theodosia Woo

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Arts and Science: On a Scientific Note

Christoforos Tsantoulas explores the relationship between music and science

Albert Einstein was not only a scientific superstar but also a talented musician

At first glance, science and music seem to have little in common with one another. Scientific research is rational, detail oriented and protocol- driven, the complete opposite of highly imaginative abstract musical creations. However, by examining these two disciplines more carefully, similarities start to emerge. There are two elementary components in music, composition and performance—the first is highly creative, while the latter requires accuracy. For instance, a musical composer must be both imaginative and precise when writing a score. In doing research, scientists must also be creative to design novel experiments or techniques but also accurate when generating and analysing their data.

Interestingly, some of the most distinguished musicians possess strong scientific backgrounds, suggesting an overlap in the skills required to succeed in music or science. Brian May, the guitarist of Queen, completed his PhD in astrophysics on light reflecting from interplanetary dust. Meanwhile, Brian Cox is probably the only pop star to become a celebrity later on for his scientific contribution. Prior to gazing at the stars and working on theoretical physics, the University of Manchester Professor was a keyboardist for the group D:Ream and even entered the UK charts with the song “Things Can Only Get Better”. Other examples include Ladytron vocalist/geneticist Dr Mira Aroyo and Dexter Holland, who gave up his PhD studies in molecular biology to focus on The Offspring. If you think the latter is pretty cool for a punk rock front man, you should also consider Bad Religion lead singer Dr Greg Graffin, who currently teaches life sciences and palaeontology at the University of California, Los Angeles. Read More »

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Behind the Science: The Notoriety of Oliver Sacks

Robin Lamboll looks at the controversial career of a neurologist who works with music

Oliver Sacks: professional neurologistd and bestselling author

It is rare for a popular science author to find themselves criticised for anything much more interesting than oversimplifying their subject. Dumbing down is not a problem many people have with Oliver Sacks, professional neurologist and bestselling author. His books are popular in the sense of being ‘accessible but enjoyed by everyone’, rather than ‘simple and containing nothing of interest for the expert’. As he opens his clinical casebook in The Man Who Mistook his Wife for a Hat, the reader explores the many curious disorders of the mind both on a personal and technical level. The reader may want to look up some of the more obscure references to the neurological principles each case brings to light, or might fall behind the scintillating analogies Sacks makes between disparate areas of medicine, literature and philosophy. However, they are likely to put the effort in—the subject is too interesting to miss out on.

Sacks originally achieved notoriety with the book Awakenings, which describes how people who suffered from sleepy sickness (encephalitic lethargica) were awoken from their decades-long sleep by the new drug L-DOPA. The book investigates how they dealt with restarting their lives after such a break from the world, the lingering effects of the illness and the many adverse effects of the drugs. The tale inspired both a film of the same name and the Harold Pinter play A Kind of Alaska. Read More »

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History: The War Against Infection

Nathan Smith explains how the pre-antibiotic era could come back to help us

John Tyndall noted the antibiotic effects of penicillin in 1875

We stand on the brink of the post-antibiotic era, with bacteria becoming increasingly resistant to existing drugs and with few new ones in the pipeline. In light of this fact, scientists are revisiting early antibiotic agents in the search for a new wonder drug with which to tackle the escalating bacterial threat. One of the most common groups of antibiotics, penicillin, only became widely available during World War II, with one of its first high profile uses taking place in the aftermath of the D-Day landings. However, researchers had first highlighted bacteria as a cause of disease about 70 years beforehand. Indeed, the history of antibiotics prior to the popularised use of penicillin is incredibly rich with attempts to find the ‘magic bullet’ against infection. Reconsideration of this early research may offer the solution to this looming medical dilemma. Read More »

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Away from the Bench: Altitude Science

Two weeks before he treks out, Elly Smith talks to Dr Andrew Murray about science on Everest

Mount Everest is the Earth's highest mountain, with a peak at 8,848 metres above sea level

At the foot of the highest mountain in the world, surrounded by rocks and ice, lies one of the most hostile environments on the planet. Here, the air is too thin for helicopters to approach; one wreckage lies sprawled against the craggy ground. Breathing is the perpetually oppressive imperative, and hypoxia drains the body’s capacity to carry out trivial physical tasks. Performance on basic mental functions, like remembering a list of 15 words or joining numbered dots, is embarrassingly impaired. Even sleeping can become arduous.

Most trekkers to Everest base camp are thrill- seekers, but Dr Andrew Murray and the Caudwell Xtreme Everest team have other purposes in mind. They are driven by the pressing need to improve care for the critically ill. In the UK, one in five of us will end up in intensive care, where the mortality rate is 40 per cent. Despite this being one of the most sophisticated areas of modern medicine, “we really don’t understand why it is that some people die and some people survive”, Dr Murray explains. “But the one thing that almost all of these patients have got in common is low oxygen levels. Equally, we don’t know why some people perform well at altitude and others get awful crippling mountain sickness.” Read More »

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Initiatives: Making New Scientists

Elizabeth Mooney reflects on the opening of the new Cambridge Science Centre

The Cambridge Science Centre on Jesus Lane opened in February 2013

Cambridge has a reputation as a world-class centre for excellence in scientific research and some of the most significant discoveries in modern times have been made here. It therefore seems obvious that as a city we should seek to inspire younger generations to explore science and make their own discoveries about how things work in the world around them. However, unlike many other cities we have never had a dedicated hands-on science museum providing these opportunities. The opening of the new Cambridge Science Centre has changed all that. Open six days a week, the Science Centre is filled with a fascinating array of hands-on exhibits ranging from infrared cameras to giant anatomical models, and also features a large magnetic wall on which complex cog and gear contraptions can be constructed. Read More »

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Science and Policy: Waste of Research

Maja Choma discusses the environmental impact of biomedical research

Recycling is becoming more important in biomedical research facilities

The UK is very proud of its large biomedical research sector, but there is a darker side to this innovative part of the economy: the amount of waste. Whether we look at the physical rubbish produced or the amount of energy used, a laboratory’s carbon footprint far exceeds that of a normal office space, shopping centre or school. The high level of safety measures required by a lab makes it unpopular with the energy-efficiency community, but it doesn’t mean that nothing can or should be done.

The majority of the rubbish may not be contaminated with anything dangerous, but it is still most likely to end up in a landfill, not recycling. Most of a lab’s bin contents have been classified as bio-hazardous and therefore as posing a threat to human health or the environment—not an enticing starting point for recycling. Read More »

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