Harmless Soil-Dwelling Bacteria Successfully Kill Cancer

A bacterial strain that specifically targets tumours could soon be used as a vehicle to deliver drugs in frontline cancer therapy. The strain is expected to be tested in cancer patients in 2013, says a scientist at the Society for General Microbiology's Autumn Conference at the University of York.

The therapy uses Clostridium sporogenes -- a bacterium that is widespread in the soil. Spores of the bacterium are injected into patients and only grow in solid tumours, where a specific bacterial enzyme is produced. An anti-cancer drug is injected separately into the patient in an inactive 'pro-drug' form. When the pro-drug reaches the site of the tumour, the bacterial enzyme activates the drug, allowing it to destroy only the cells in its vicinity -- the tumour cells.

Researchers at the University of Nottingham and the University of Maastricht have now overcome the hurdles that have so far prevented this therapy from entering clinical trials. They have introduced a gene for a much-improved version of the enzyme into the C. sporogenes DNA. The improved enzyme can now be produced in far greater quantities in the tumour than previous versions, and is more efficient at converting the pro-drug into its active form.

A fundamental requirement for any new cancer therapy is the ability to target cancer cells while excluding healthy cells. Professor Nigel Minton, who is leading the research, explains how this therapy naturally fulfils this need. "Clostridia are an ancient group of bacteria that evolved on the planet before it had an oxygen-rich atmosphere and so they thrive in low oxygen conditions. When Clostridia spores are injected into a cancer patient, they will only grow in oxygen-depleted environments, i.e. the centre of solid tumours. This is a totally natural phenomenon, which requires no fundamental alterations and is exquisitely specific. We can exploit this specificity to kill tumour cells but leave healthy tissue unscathed," he said.

The research may ultimately lead to a simple and safe procedure for curing a wide range of solid tumours. "This therapy will kill all types of tumour cell. The treatment is superior to a surgical procedure, especially for patients at high risk or with difficult tumour locations," explained Professor Minton. "We anticipate that the strain we have developed will be used in a clinical trial in 2013 led by Jan Theys and Philippe Lambin at the University of Maastricht in The Netherlands. A successful outcome could lead to its adoption as a frontline therapy for treating solid tumours. If the approach is successfully combined with more traditional approaches this could increase our chance of winning the battle against cancerous tumours."

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Scientists Uncover Secrets of How Intellect and Behavior Emerge During Childhood

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown that a single protein plays an oversized role in intellectual and behavioral development. The scientists found that mutations in a single gene, which is known to cause intellectual disability and increase the risk of developing autism spectrum disorder, severely disrupts the organization of developing brain circuits during early childhood. This study helps explain how genetic mutations can cause profound cognitive and behavioral problems.

The study was published in the Nov. 9, 2012, issue of the journal Cell.

The genetic mutations that cause developmental disorders, such as intellectual disability and autism spectrum disorder, commonly affect synapses, the junctions between two nerve cells that are part of the brain's complex electro-chemical signaling system. A substantial percentage of children with severe intellectual and behavioral impairments are believed to harbor single mutations in critical neurodevelopmental genes. Until this study, however, it was unclear precisely how pathogenic genetic mutations and synapse function were related to the failure to develop normal intellect.

"In this study, we did something no one else had done before," said Gavin Rumbaugh, a TSRI associate professor who led the new research. "Using an animal model, we looked at a mutation known to cause intellectual disability and showed for the first time a causative link between abnormal synapse maturation during brain development and life-long cognitive disruptions commonly seen in adults with a neurodevelopmental disorder."

Losing Balance

The study focused on a critical synaptic protein known as SynGAP1. Mutations in the gene that encodes this protein cause disabilities in an estimated one million people worldwide, according to the paper.

"There are a few genes that can't be altered without affecting normal cognitive abilities," Rumbaugh said. "SynGAP1 is one of the most important genes in cognition -- so far, every time a mutation that disrupts the function of SynGAP1 has been found, that individual's brain simply could not develop correctly. It regulates the development of synaptic function like no other gene I've seen."

Using animal models that were missing just one copy of SynGAP1, as seen in some patients with intellectual disability, the scientists found that certain synapses develop prematurely in the period shortly after birth. This dramatically enhances what is known as "excitability" -- how often brain cells fire -- in the developing hippocampus, a part of the brain critical for memory. The balance between excitability and inhibition is especially critical during early developmental periods, when neural connections that ultimately give rise to normal cognitive and behavioral functions are forming.

"You might think this accelerated development of brain circuits would make you smarter," Rumbaugh said. "But the increased excitability actually disorganizes brain development. We think that early maturation of these excitatory synapses disrupts the timing of later developmental milestones. It rains down chaos on this complex process, preventing normal intellectual and behavioral development."

A Critical Window

Interestingly, inducing these mutations after the critical development period was complete had virtually no impact on normal synapse function and repairing these pathogenic mutations in adulthood did not improve behavior or cognition.

"A key finding is we were able to remove the mutation and restore SynGAP protein levels in adult mice with obvious cognitive and behavioral problems, but this intervention did not benefit the animals," Rumbaugh said.

These results imply that very early intervention is essential in neurodevelopmental disorders, particularly for cognitive problems. The team is now aggressively searching for the optimal period during development in which repairing these mutations is most beneficial.

Rumbaugh speculates that successfully defining these treatment windows, combined with the fast-approaching ability to identify potential pathogenic mutations in utero, will provide a possible path toward eradicating this type of intellectual disability and lowering the risks for autism. "We believe a cure is possible," he said. "It is likely that there are many other single mutations out there that cause distinct forms of these spectrum disorders. Our strategy could be applied to these disorders as well."

The first author of the study, "Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting the Maturation of Dendritic Spine Synapses," is James Clement of TSRI. Other authors include Massimiliano Aceti, Thomas Creson, Emin D Ozkan, Brooke Miller, and Courtney A. Miller of TSRI; Yulin Shi and Xiangmin Xu of The University of California, Irvine; Nicholas Reis and Antoine Almonte of The University of Alabama at Birmingham; and Brian Wiltgen of The University of Virginia.

The study was funded by the National Institute for Neurological Disorders and Stroke (R01NS064079), the Eunice Kennedy Shriver National Institute for Child Health and Human Development (R03HD060672), the National Alliance for Research on Schizophrenia and Depression, and the National Institute for Drug Abuse (DA023700-04S1).

Journal Reference:

1.      James P. Clement, Massimiliano Aceti, Thomas K. Creson, Emin D. Ozkan, Yulin Shi, Nicholas J. Reish, Antoine G. Almonte, Brooke H. Miller, Brian J. Wiltgen, Courtney A. Miller, Xiangmin Xu, Gavin Rumbaugh. Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses.Cell, 2012; 151 (4): 709 DOI: 10.1016/j.cell.2012.08.045

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New Strategy for Fingerprint Visualization Developed

Identifying fingerprints on paper is a commonly used method in police forensic work, but unfortunately it is not easy to make those fingerprints visible. Now, scientists at the Hebrew University of Jerusalem have developed a new approach for making such fingerprints more readily readable.

The new method, created by a team headed by Prof. Yossi Almog and Prof. Daniel Mandler of the Institute of Chemistry at the Hebrew University, uses an innovative chemical process to produce a negative of the fingerprint image rather than the positive image produced under current methods. Unlike the latter, the Hebrew University-developed process is nearly independent of the composition of the sweat residue left behind on the paper.

The new method is described in the current issue of the international, English-language edition of the journal Angewandte Chemie, published by the German Chemical Society.

In many criminal investigations, paper evidence plays an important role, and it is useful to know who has handled such documents as checks, paper currency, notes, etc. Studies have shown that less than half of the fingerprints on paper items can be made sufficiently visible to enable their identification. The main reason for this seems to be the highly variable composition of the sweat left behind on the paper.

The new procedure developed at the Hebrew University avoids these problems. It involves an inversion of an established method in which gold nanoparticles are first deposited onto the invisible fingerprints, followed by elemental silver, similar to the development of a black and white photograph.

In the conventional technique, the gold particles get stuck to the amino acid components of the sweat in the fingerprints, and then silver is deposited onto the gold. The result is quite often low-contrast impressions of the fingerprints. In the new method, the gold nanoparticles stick directly to the paper surface, but not the sweat. This technique utiliizes the sebum from the fingerprints as a medium to avoid this interference. (Sebum is an oily substance secreted by the sebaceous glands that helps prevent hair and skin from drying out.) Treatment with a developer containing silver then turns the areas with gold on them black, resulting in a clear, negative image of the fingerprint.

"Since our method relies only on the fatty components in the fingerprints, the sweaty aspects play no role in the imaging process," said Prof. Almog. This technique also promises to alleviate another problem, he said. "If paper has become wet, it has previously been difficult to detect fingerprints because the amino acids in the sweat, which are the primary substrate for current chemical enhancement reactions, are dissolved and washed away by water, whereas the fatty components are barely affected." Thus, the avoidance of the sweat aspect provides a further enhancement for police laboratory investigation, he observed.

Journal Reference:

1.      Nimer Jaber, Adam Lesniewski, Hadar Gabizon, Sanaa Shenawi, Daniel Mandler, Joseph Almog. Visualization of Latent Fingermarks by Nanotechnology: Reversed Development on Paper-A Remedy to the Variation in Sweat Composition. Angewandte Chemie International Edition, 2012; DOI: 10.1002/anie.201205259

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Virtual Reality Puts Human in Rat World: 'Beaming' Technology Transforms Human-Animal Interaction

Using cutting-edge virtual reality technology, researchers have 'beamed' a person into a rat facility allowing the rat and human to interact with each other on the same scale.

Published October 31 in PLOS ONE, the research enables the rat to interact with a rat-sized robot controlled by a human participant in a different location. At the same time, the human participant (who is in a virtual environment) interacts with a human-sized avatar that is controlled by the movements of the distant rat. The authors hope the new technology will be used to study animal behaviour in a completely new way.

Computer scientists at UCL and the University of Barcelona have been working on the idea of 'beaming' for some time now, having last year digitally beamed a scientist in Barcelona to London to be interviewed by a journalist.

The researchers define 'beaming' as digitally transporting a representation of yourself to a distant place, where you can interact with the people there as if you were there. This is achieved through a combination of virtual reality and teleoperator systems. The visitor to the remote place (the destination) is represented there ideally by a physical robot.

During the human-animal beaming process the human participants in the system were in a virtual reality lab at the Mundet campus of the University of Barcelona. The rat was located around 12 km away in an animal care facility in Bellvitge.

Tracking technology was used to track the movements of the rat in its arena, and the tracking data was transmitted over the internet to the computers running the virtual reality simulation in Mundet. This tracking information was used to control a virtual human character (an avatar) that represented the rat so that whenever the rat moved its avatar moved too, in a representation of the rat arena but scaled up to human size. Hence the human participant shared the virtual arena, which looked like a room with some pictures on the walls, with a humanoid avatar.

The movements of the human in the virtual reality were also tracked, and the data sent to computers in Bellvitge that controlled a small robot that was located in the rat arena. Whenever the human moved in the virtual space the robot moved in the rat space.

Putting all this together -- the rat interacted with a rat sized robot that represented the remotely located human, and the human interacted with a human sized avatar that represented the remotely located rat.

Professor Mandayam Srinivasan, author of the paper from the UCL Department of Computer Science and MIT, said: "Beaming is a step beyond approaches such as video conferencing which do not give participants the physical sensation of being in the same shared space, and certainly not the physical capability to actually carry out actions in that space."

He added: "The process demonstrated here not only shows the range of our technology, but also provides a new tool for scientists, explorers or others to visit distant and alien places without themselves being placed in any kind of danger, and importantly, to be able to see animal behavior in a totally new way -- as if it were the behavior of humans."

Professor Mel Slater, also from the UCL Department of Computer Science and also ICREA, University of Barcelona said: "In the paper we used the idea of representing the rat as if it were a human, but there would be many other possibilities. One idea is that using this technology behavioural scientists could get insights into behavior by observing it, and taking part in it, through this quite different filter. However, our primary goal was to demonstrate the possibilities inherent in this technology."

Journal Reference:

1.      Jean-Marie Normand, Maria V. Sanchez-Vives, Christian Waechter, Elias Giannopoulos, Bernhard Grosswindhager, Bernhard Spanlang, Christoph Guger, Gudrun Klinker, Mandayam A. Srinivasan, Mel Slater. Beaming into the Rat World: Enabling Real-Time Interaction between Rat and Human Each at Their Own Scale. PLoS ONE, 2012; 7 (10): e48331 DOI: 10.1371/journal.pone.0048331

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Mummy Unwrapping Brought Egyptology to the Public

Mummies have been objects of horror in popular culture since the early 1800's -- more than a century before Boris Karloff portrayed an ancient Egyptian searching for his lost love in the 1932 film "The Mummy." Public "unwrappings" of real mummified human remains performed by both showmen and scientists heightened the fascination, but also helped develop the growing science of Egyptology, says a Missouri University of Science and Technology historian.

Dr. Kathleen Sheppard, an expert in the history of science, particularly archaeology and Egyptology, and an assistant professor of history and political science at Missouri S&T, says that while mummy unwrappings served as public spectacles that objectified exotic artifacts, they were also scientific investigations that sought to reveal medical and historical information about ancient life.

Sheppard wrote about this intersection between science and showmanship in an article titled "Between Spectacle and Science: Margaret Murray and the Tomb of the Two Brothers." It will be published in the December issue of the journalScience in Context.

Sheppard says 20th century Egyptologist Margaret Murray, the first woman to publicly unwrap a mummy, sought to unravel the mysteries of ancient Egypt by exposing mummified human remains. She says Murray's work is culturally significant because it is "poised between spectacle and science, drawing morbid public interest while also producing ground-breaking scientific work that continues to this day."

Public spectacles that displayed mummified remains as objects of curiosity date back to the 16th century, Sheppard says. "These types of spectacles were highly engaging shows in which people were, to a certain degree, educated about different aspects of science both by showmen and scientists."

Many Egyptologists drew a distinction between "Egyptomania," the fascination with all things Egypt, and "Egyptology," the scientific study of Egyptian life, Sheppard says, but Murray had a different goal -- involving the public in scientific inquiry with a goal of correcting popular misconceptions.

"Murray tried to get the public to see that mummies weren't magical, they were just preserved human remains to be studied and learned from," Sheppard says. "In other words, rather than trying to separate the 'mania' from the 'ology,' she wanted to bring reason and understanding to the mania."

Journal Reference:

1.      Kathleen L. Sheppard. Between Spectacle and Science: Margaret Murray and the Tomb of the Two Brothers.Science in Context, 2012; 25 (04): 525 DOI:10.1017/S0269889712000221

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New Device Could Allow Your Heartbeat to Power Pacemaker

An experimental device converted energy from a beating heart to provide enough electricity to power a pacemaker, in a study presented at the American Heart Association's Scientific Sessions 2012.

The findings suggest that patients could power their pacemakers -- eliminating the need for replacements when batteries are spent.

In a preliminary study, researchers tested an energy-harvesting device that uses piezoelectricity -- electrical charge generated from motion. The approach is a promising technological solution for pacemakers, because they require only small amounts of power to operate, said M. Amin Karami, Ph.D., lead author of the study and research fellow in the Department of Aerospace Engineering at the University of Michigan in Ann Arbor.

Piezoelectricity might also power other implantable cardiac devices like defibrillators, which also have minimal energy needs, he said.

Today's pacemakers must be replaced every five to seven years when their batteries run out, which is costly and inconvenient, Karami said.

"Many of the patients are children who live with pacemakers for many years," he said. "You can imagine how many operations they are spared if this new technology is implemented."

Researchers measured heartbeat-induced vibrations in the chest. Then, they used a "shaker" to reproduce the vibrations in the laboratory and connected it to a prototype cardiac energy harvester they developed. Measurements of the prototype's performance, based on sets of 100 simulated heartbeats at various heart rates, showed the energy harvester performed as the scientists had predicted -- generating more than 10 times the power than modern pacemakers require.

The next step will be implanting the energy harvester, which is about half the size of batteries now used in pacemakers, Karami said. Researchers hope to integrate their technology into commercial pacemakers.

Two types of energy harvesters can power a typical pacemaker: linear and nonlinear. Linear harvesters work well only at a specific heart rate, so heart rate changes prevent them from harvesting enough power.

In contrast, a nonlinear harvester -- the type used in the study -- uses magnets to enhance power production and make the harvester less sensitive to heart rate changes. The nonlinear harvester generated enough power from heartbeats ranging from 20 to 600 beats per minute to continuously power a pacemaker.

Devices such as cell phones or microwave ovens would not affect the nonlinear device, Karami said.

Co-authors are David J. Bradley, M.D., and Daniel J. Inman, Ph.D.

The National Institute of Standards and Technology and National Center for Advancing Translational Sciences funded the study.

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Super-Massive Black Hole Inflates Giant Bubble

Like symbiotic species, a galaxy and its central black hole lead intimately connected lives. The details of this relationship still pose many puzzles for astronomers.

This false colour image shows the galaxy M87. Optical light is shown in white/blue (SDSS), the radio emission in yellow/orange (LOFAR). At the centre, the radio emission has a very high surface brightness, showing where the jet powered by the supermassive black hole is located. (Credit: Francesco de Gasperin, on behalf of the LOFAR collaboration)

 Some black holes actively accrete matter. Part of this material do not fall into the black hole but is ejected in a narrow stream of particles, traveling at nearly the speed of light. When the stream slows down, it creates a tenuous bubble that can engulf the entire galaxy. Invisible to optical telescopes, the bubble is very prominent at low radio frequencies. The new International LOFAR Telescope - designed and built by ASTRON in an international collaboration - is ideally suited to detect this low frequency emission.

Astronomers have produced one of the best images ever of such a bubble, using LOFAR to detect frequencies from 20 to 160 MHz. "The result is of great importance", says Francesco de Gasperin, lead author of the study that is being published in the journal Astronomy & Astrophysics. "It shows the enormous potential of LOFAR, and provides compelling evidence of the close ties between black hole, host galaxy, and their surroundings."

The image was made during the test-phase of LOFAR, and targeted the giant elliptical galaxy Messier 87, at the centre of a galaxy cluster in the constellation of Virgo. This galaxy is 2000 times more massive than our Milky Way and hosts in its centre one of the most massive black holes discovered so far, with a mass six billion times that of our Sun. Every few minutes this black hole swallows an amount of matter similar to that of the whole Earth, converting part of it into radiation and a larger part into powerful jets of ultra-fast particles, which are responsible for the observed radio emission.

“This is the first time such high-quality images are possible at these low frequencies", says professor Heino Falcke, chairman of the board of the ILT and co-author of the study. "This was a challenging observation - we did not expect to get such fantastic results so early in the commissioning phase of LOFAR."

To determine the age of the bubble, the authors added radio observations at different frequencies from the Very Large Array in New Mexico (USA), and the Effelsberg 100-meter radio telescope near Bonn (Germany). The team found that this bubble is surprisingly young, just about 40 million years, which is a mere instant on cosmic time scales. The low frequency observation does not reveal any relic emission outside the well-confined bubble boundaries, this means that the bubble is not just a relic of an activity that happened long ago but is constantly refilled with fresh particles ejected by the central black hole.

"What is particularly fascinating", says Andrea Merloni from the Max-Planck Institute of Extraterrestrial Physics in Garching, who supervised de Gasperin's doctoral work, "is that the results also provide clues on the violent matter-to-energy conversion that occurs very close to the black hole. In this case the black hole is particularly efficient in accelerating the jet, and much less effective in producing visible emission."

Francesco de Gasperin performed the study as part of his PhD work at the Max Planck Institute for Astrophysics and at the Excellence Cluster Universe. De Gasperin is now a postdoctoral researcher at the University of Hamburg.

Journal Reference:

1.      F. de Gasperin, E. Orrú, M. Murgia, A. Merloni, H. Falcke, R. Beck, R. Beswick, L. Bîrzan, A. Bonafede, M. Brüggen, G. Brunetti, K. Chyży, J. Conway, J. H. Croston, T. Enßlin, C. Ferrari, G. Heald, S. Heidenreich, N. Jackson, G. Macario, J. McKean, G. Miley, R. Morganti, A. Offringa, R. Pizzo, D. Rafferty, H. Röttgering, A. Shulevski, M. Steinmetz, C. Tasse, S. van der Tol, W. van Driel, R. J. van Weeren, J. E. van Zwieten, A. Alexov, J. Anderson, A. Asgekar, M. Avruch, M. Bell, M. R. Bell, M. Bentum, G. Bernardi, P. Best, F. Breitling, J. W. Broderick, A. Butcher, B. Ciardi, R. J. Dettmar, J. Eisloeffel, W. Frieswijk, H. Gankema, M. Garrett, M. Gerbers, J. M. Griessmeier, A. W. Gunst, T. E. Hassall, J. Hessels, M. Hoeft, A. Horneffer, A. Karastergiou, J. Köhler, Y. Koopman, M. Kuniyoshi, G. Kuper, P. Maat, G. Mann, M. Mevius, D. D. Mulcahy, H. Munk, R. Nijboer, J. Noordam, H. Paas, M. Pandey, V. N. Pandey, A. Polatidis, W. Reich, A. P. Schoenmakers, J. Sluman, O. Smirnov, C. Sobey, B. Stappers, J. Swinbank, M. Tagger, Y. Tang, I. van Bemmel, W. van Cappellen, A. P. van Duin, M. van Haarlem, J. van Leeuwen, R. Vermeulen, C. Vocks, S. White, M. Wise, O. Wucknitz, P. Zarka. M 87 at metre wavelengths: the LOFAR picture.Astronomy & Astrophysics, 2012; 547: A56 DOI:10.1051/0004-6361/201220209

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