What causes brain cancer?

Glioblastoma is the most common and most lethal form of brain tumor in people. Research published in the International Journal of Computational Biology and Drug Design offers a novel way to determine what biological functions go awry when the tumor first begins to form. Understanding the problems at the molecular level might one day reveal the underlying mechanism of carcinogenesis in glioblastoma and ultimately lead to treatments or even preventative measures.

This form of brain tumor account for more than half of all cases in which the tumor is within the tissues of the brain and a fifth of cases in which a tumor is present within the skull.

Zhongming Zhao and colleagues at Vanderbilt University, in Tennessee, explain how problems that occur during the transcription of the genetic code for making proteins may play a role in the formation of a glioblastoma. These might arise through changes in the genetic materials itself or alterations to the molecules involved in regulating the transcription process. In their latest research, the team has tested the possibility that microRNAs (miRNAs) and transcription factors (TFs) might somehow regulate the genes glioblastoma. With this in mind, the researchers carried out a computer search of appropriate databases to uncover any links between these components of the genetic machinery and glioblastoma.

Although cancer exists in many different forms and is not a single disease but a complex array of different diseases, there are certain characteristics that define the different forms: self-sufficiency in growth signals, insensitivity to antigrowth signals, evading programmed cell death, limitless replicative potential of cells, sustained blood-vessel growth, evasion of the immune system, tissue invasion and spreading through the body in metastasis. Insights into these processes at the molecular level is now possible thanks to the advent of vast databases of genomic and biochemical information related to different types of cancer.

The Vanderbilt team has now searched three databases miR2Disease, HMDD (human miRNA-associated disease database) and PhenomiR, to find regulatory networks specific to glioblastoma. To do so they integrated data on glioblastoma-related miRNAs, TFs and genes. They utilized a well-known target-prediction tool, TargetScan, to trawl the databases and identified 54 so-called feed-forward loops (FFLs), these are molecular control systems involved in transcription and the required signaling processes. Follow up work revealed these FFLs to have functions important to carcinogenesis as well as unique functions specific to each FFL.

“Our work provided data for future investigation of the mechanisms underlying glioblastoma and also potential regulatory subunits that might be useful for biomarker discovery and therapy targets for glioblastoma,” the team concludes.

Gong, X., Sun, J., & Zhao, Z. (2011). Gene regulation in glioblastoma: a combinatorial analysis of microRNAs and transcription factors International Journal of Computational Biology and Drug Design, 4 (2) DOI: 10.1504/IJCBDD.2011.041006

Emulating nature for better engineering

UK researchers describe a novel approach to making porous materials, solid foams, more like their counterparts in the natural world, including bone and wood in the new issue of the International Journal of Design Engineering.

According to Carmen Torres-Sanchez of the Department of Mechanical Engineering, at Heriot-Watt University, Edinburgh and Jonathan Corney of the Department of Design, Manufacture and Engineering Management, at the University of Strathclyde, Glasgow in the natural world, the graduated distribution of porosity has evolved so that nature might transfer forces and minimise stresses to avoid whole structure failure. For instance, a crack in the branch of a tree will not lead to the felling of the tree in the same way that a broken ankle will not lead to collapse of the whole leg. “Porosity gradation is an important functionality of the original structure that evolution has developed in a trial and error fashion,” the team explains.

It is not just tree trunks and bones that have evolved graduated porosity, beehives, marine sponges, seashells, teeth, feathers and countless other examples display this characteristic. Researchers would like to be able to emulate the way in which nature has evolved solutions to the perennial issues facing engineers. In so doing, they will be able to develop structures that use the least amount of material to gain the lowest density structure and so the maximum strength-to-weight ratio.

“Many engineering applications, such as thermal, acoustics, mechanical, structural and tissue engineering, require porosity tailored structures,” the team says. If materials scientists could develop porous materials that closely mimic nature’s structural marvels, then countless engineering problems including bridge building and construction in earthquake zones, improved vehicle and aircraft efficiency and even longer-lasting more biocompatible medical prosthetics might be possible.

Unfortunately, current manufacturing methods for making porous materials cannot mass-produce graduated foams. The collaborators in Scotland, however, have turned to low power-low frequency ultrasonic irradiation that can “excite” molten polymers as they begin to foam and once solidify effectively trap within their porous structure different porosity distributions throughout the solid matrix. This approach allowed the team to generate polymeric foams with porosity gradients closely resembling natural cellular structures, such as bones and wood. The technology opens up new opportunities in the design and manufacture of bio-mimetic materials that can solve challenging technological problems, the team adds.

The researchers anticipate that using more sophisticated ultrasound energy sources as well as chemical coupling agents in the molten starting material will allow them to fine tune the formation of pores in the material. This is an area of current interest because it would facilitate the design of novel texture distributions or replicate more closely nature porous materials, the team concludes.

Sanchez, C., & Corney, J. (2011). A novel manufacturing strategy for bio-inspired cellular structures International Journal of Design Engineering, 4 (1) DOI: 10.1504/IJDE.2011.041406

Flat-packed particles

Graphene, a Manchester University discovery, is a material comprising sheets of carbon just one atom thick; graphene is like a single layer of graphite. However, it was the discovery that it has some peculiar electronic properties because of the existence of massless quasiparticles that has led to an explosion of interest in this material. Some researchers suggest that ultimately it will become the material that gives us a post-silicon world in computing.

Now, US scientists have made the first observation of the energy bands of complex particles within graphene known as plasmarons. This small step is an important one in understanding graphene and using it to develop devices for that future of ultrafast chemical computers.

At Berkeley Lab’s Advanced Light Source, an international team led by Aaron Bostwick and Eli Rotenberg have shown that these composite plasmaron particles are vital in generating graphene’s unique properties. “Graphene’s true electronic structure can’t be understood without understanding the many complex interactions of electrons with other particles.”

The electric charge carriers in graphene are negative electrons and positive holes, which in turn are affected by plasmons, oscillations in the density of the material that travel like sound waves through a sea of electrons. A plasmaron is “simply” a charge carrier coupled to a plasmon. “Although plasmarons were proposed theoretically in the late 1960s, and indirect evidence for them has been found, our work is the first observation of their distinct energy bands in graphene, or indeed in any material,” Rotenberg says. The team reported details of their findings in the journal Science in May.

Top: graphene structure. Bottom: a theoretical model of plasmaron interactions in graphene, sheets of carbon one atom thick.

The relationships between charge carriers, plasmons, and plasmarons will be important in the development of plasmonics, the architecture analogous to electronics in conventional silicon semiconductor circuitry. An important aspect of studying these relationships is to produce flat graphene sheets; graphene is usually rumpled like unmade bed linen. “One of the best ways to grow a flat sheet of graphene is by heating a crystal of silicon carbide,” Rotenberg explains, “and it happens that our German colleagues Thomas Seyller from the University of Erlangen and Karsten Horn from the Fritz Haber Institute in Berlin are experts at working with silicon carbide. As the silicon recedes from the surface it leaves a single carbon layer.”

With flat graphene sheets in hand, the team used a beam of low-energy, or soft, X-rays to analyse the materials. The resulting data provided them with an image of the electronic bands created by the electrons themselves. Even from the initial experiments, the team suspected graphene’s behaviour was more complicated than simple theory would suggest and seemed to hint at the existence of bare electrons. Since bare electrons cannot exist, the researchers postulated the fuzziness in their image was due to charge carriers emitting plasmons. Additional experiments with graphene sheets isolated from their support material revealed that electrons detached by the X-rays can leave behind either an ordinary hole or a hole bound to a plasmon – a plasmaron, explains Rotenberg.

“By their nature, plasmons couple strongly to photons, which promises new ways for manipulating light in nanostructures, giving rise to the field of plasmonics,” Rotenberg says. “Now we know that plasmons couple strongly to the charge carriers in graphene, which suggests that graphene may have an important role to play in the merging fields of electronics, photonics, and plasmonics on the nanoscale.”


Science, 2010, 328, 999-1002
Eli Rotenberg homepage