Diagnosis and treatment insights for an unusual childhood Cancer Syndrome An unusual case of a young girl with a colon cancer syndrome caused by recessive mutations in the mismatch repair gene MSH6 is described in the February issue of Nature Clinical Practice Oncology. Individuals with mutations in MSH6 are at an increased risk of developing cancer; however, a childhood cancer syndrome caused by these mutations has only recently been recognized.In this article, Richard Scott and colleagues report how a 13-year-old girl who was treated for a brain tumor and leukemia was subsequently diagnosed with multiple colon cancers and skin lesions, despite an absence of hereditary colon cancer. Recessive mutations in the MSH6 gene were identified in this patient and she was successfully treated with surgery and chemotherapy.This case study broadens the tumor spectrum associated with recessive MSH6 mutations and discusses the implications for treatment in such individuals. Many mismatch repair deficiency syndromes are treated with the drug temozolomide, but preclinical and clinical data show that it can cause resistance and may promote further genetic abnormality. Mutations in MSH6 and other mismatch repair genes should be considered in any child presenting with malignancy and abnormal skin pigmentation. Early diagnosis is important so that genetic testing and screening can be offered to relatives, and could also help avoid ineffective chemotherapeutic agents such as temozolomide.
Author contact:Richard Scott (Institute of Cancer Research, Surrey, UK)Tel: +44 208 7224 455; E-mail: richard.scott@icr.ac.uk Editor contact:Lisa Hutchinson (Editor, Nature Clinical Practice Oncology)Tel: +44 20 7843 4837; Email: l.hutchinson@nature.com

Gene Segment Identified in Virulent Human H5N1 Viruses
Key discovery may enable development of vaccines, therapeutics
BOSTON, Jan. 27, 2007 -- Viruses whose genomes constantly mutate, such as the H5N1 "bird flu," are driving a race to find relatively unchanging segments of their genomes; successful identification of these segments may allow more successful vaccines and therapeutics to be developed. Replikins are short fragments of the genomes of infectious organisms, which have been found to be related quantitatively to rapid replication and epidemic outbreaks (1,2). Scientists at Replikins, LLC have just identified a specific site in the human H5N1 virus genome which contains a dramatically higher concentration of replikins than the rest of the virus, and named it the Replikin Peak Gene(TM) (RPG). Two of the replikin components of RPG have been found to be conserved over 88 years in the following high-mortality and pandemic virus strains: H1N1, H2N2, H3N2, H5N1, and H7N7. This discovery makes possible very specific targeting with vaccines and other treatments; these Replikin peptides also form the basis for a pan-strain influenza vaccine, for which trials are underway. New quantitative virus protein sequence search software, FluForecast(R), available as a service from Replikins Ltd., was central to this work. RPG was isolated by comparing the replikin concentration (Replikin Count(TM)) of RPG to seven other defined areas of the H5N1 genome (Figure). The Replikin Count(TM) of RPG, was found to be associated with the pB1 area of the human H5N1 virus genome, and was increased tenfold from 2003 to 2006, during the current bird flu epidemics, when it was 4 to 10 times greater than that of the other genomic sections of the virus (hemagglutinin, neuraminidase, pA, pB2, ns, matrix, nucleocapsid)(p<0.001). In contrast to 'in vivo' or 'in vitro' localization of a gene, this method may be thought of as "in silico" identification or isolation of a gene. References:
1. BogochS, BogochES. Replikins: The Chemistry of Rapid
Replication. Begell Press, New York, 2005.
2. http://www.replikins.com

Smart Nanocarriers to Combat Tumors

IBN’s technology spells hope for cancer patients who suffer from painful side-effects of chemotherapy

SINGAPORE – A ‘smart’ nanocarrier technology developed by a team of researchers at the Institute of Bioengineering and Nanotechnology (IBN) is set to vastly improve the way cancer patients are treated.
Anticancer drugs are now being administered to patients using methods that cause the indiscriminate killing of both diseased and healthy cells. Such chemotherapy leads to side-effects, such as nausea, fatigue, and hair loss, and makes the patient weak and frail. Between 1998 and 2002, 38,447 people in Singapore were diagnosed with some type of cancer, while 20,289 died of the disease. Hence, there is a crucial need for the development of more effective cancer therapy, which not only minimizes side-effects but also directly targets diseased cells.
Scientists at IBN have found a way to tackle this problem through the use of anticancer drug delivery vehicles that transport drugs only to where they are needed in the body. This method significantly reduces or even eliminates the severe side-effects typically induced by conventional chemotherapeutics.
The team led by IBN Group Leader Dr Yi-Yan Yang has created ‘smart’ nanocarriers that can house anticancer drugs in their inner cores. Such polymeric core-shell nanoparticles are small in size (generally less than 200 nm), with shells that protect enclosed bioactive compounds against degradation and digestive fluids.
These nanocarriers, which are both pH-sensitive and temperature-sensitive, are structurally stable in the normal physiological environment. However, in slightly acidic environments that are characteristic of tumor tissues and endosomes (a cell component), they deform and precipitate, thus releasing the enclosed drug molecules.
“Previous attempts by other scientists involved the use of core-shell nanoparticles that were only sensitive to temperature. Drug delivery may be controlled by superficially heating and cooling the environment of the nanoparticles,” said lead scientist Dr Yang.
“The novelty of our invention compared to carriers that are only temperature-sensitive is the ability of IBN’s core-shell nanoparticles to target drugs to deep tissues or cell compartments without changes in temperature.”
Dr Yang explained that once IBN’s ‘smart’ nanocarriers encounter cancer tissues, they form a hydrophobic shell that allows them to adhere to tumor sites. Biological signals are also tagged onto the shell of these nanoparticles, enabling them to recognize and zoom in on tumor sites. After being taken up by cancer cells, the nanocarriers can absorb protons in the endosomes and release their payload into the cell’s cytoplasm, and subsequently its nucleus.
So far, the IBN team has proven that their core-shell nanoparticles can deliver anticancer drugs much more efficiently into cancer cells, compared to current techniques. Their in vivo studies using a mouse breast tumor model has also shown that doxorubicin (an anti-cancer drug) loaded in these smart nanoparticles can suppress tumor growth more efficiently than free doxorubicin.
“IBN’s ‘smart’ nanocarriers do not show significant cytotoxicity, and offer great potential in targeting drugs to tumor tissues with high efficacy,” added Dr Yang. “This invention may also be used in in vitro and animal studies for drug discovery.”
The prospects for IBN’s technology are significant, with the cancer drug delivery market expected to grow to US$15.4 billion by the year 2007.
The team’s findings were recently published in the leading journal Advanced Materials (1), and a United States patent has been filed on the invention.
(1) K. S. Soppimath, C. W. Tan and Y. Y. Yang, "pH-Triggered Thermally Responsive Polymer Core-Shell Nanoparticles for Targeted Drug Delivery", Advanced Materials 17 (2005) 318-323.
For more information on IBN, please log on to www.ibn.a-star.edu.sg.

Smart Nanocarriers to Combat Tumors

IBN’s technology spells hope for cancer patients who suffer from painful side-effects of chemotherapy

SINGAPORE – A ‘smart’ nanocarrier technology developed by a team of researchers at the Institute of Bioengineering and Nanotechnology (IBN) is set to vastly improve the way cancer patients are treated.
Anticancer drugs are now being administered to patients using methods that cause the indiscriminate killing of both diseased and healthy cells. Such chemotherapy leads to side-effects, such as nausea, fatigue, and hair loss, and makes the patient weak and frail. Between 1998 and 2002, 38,447 people in Singapore were diagnosed with some type of cancer, while 20,289 died of the disease. Hence, there is a crucial need for the development of more effective cancer therapy, which not only minimizes side-effects but also directly targets diseased cells.
Scientists at IBN have found a way to tackle this problem through the use of anticancer drug delivery vehicles that transport drugs only to where they are needed in the body. This method significantly reduces or even eliminates the severe side-effects typically induced by conventional chemotherapeutics.
The team led by IBN Group Leader Dr Yi-Yan Yang has created ‘smart’ nanocarriers that can house anticancer drugs in their inner cores. Such polymeric core-shell nanoparticles are small in size (generally less than 200 nm), with shells that protect enclosed bioactive compounds against degradation and digestive fluids.
These nanocarriers, which are both pH-sensitive and temperature-sensitive, are structurally stable in the normal physiological environment. However, in slightly acidic environments that are characteristic of tumor tissues and endosomes (a cell component), they deform and precipitate, thus releasing the enclosed drug molecules.
“Previous attempts by other scientists involved the use of core-shell nanoparticles that were only sensitive to temperature. Drug delivery may be controlled by superficially heating and cooling the environment of the nanoparticles,” said lead scientist Dr Yang.
“The novelty of our invention compared to carriers that are only temperature-sensitive is the ability of IBN’s core-shell nanoparticles to target drugs to deep tissues or cell compartments without changes in temperature.”
Dr Yang explained that once IBN’s ‘smart’ nanocarriers encounter cancer tissues, they form a hydrophobic shell that allows them to adhere to tumor sites. Biological signals are also tagged onto the shell of these nanoparticles, enabling them to recognize and zoom in on tumor sites. After being taken up by cancer cells, the nanocarriers can absorb protons in the endosomes and release their payload into the cell’s cytoplasm, and subsequently its nucleus.
So far, the IBN team has proven that their core-shell nanoparticles can deliver anticancer drugs much more efficiently into cancer cells, compared to current techniques. Their in vivo studies using a mouse breast tumor model has also shown that doxorubicin (an anti-cancer drug) loaded in these smart nanoparticles can suppress tumor growth more efficiently than free doxorubicin.
“IBN’s ‘smart’ nanocarriers do not show significant cytotoxicity, and offer great potential in targeting drugs to tumor tissues with high efficacy,” added Dr Yang. “This invention may also be used in in vitro and animal studies for drug discovery.”
The prospects for IBN’s technology are significant, with the cancer drug delivery market expected to grow to US$15.4 billion by the year 2007.
The team’s findings were recently published in the leading journal Advanced Materials (1), and a United States patent has been filed on the invention.
(1) K. S. Soppimath, C. W. Tan and Y. Y. Yang, "pH-Triggered Thermally Responsive Polymer Core-Shell Nanoparticles for Targeted Drug Delivery", Advanced Materials 17 (2005) 318-323.
For more information on IBN, please log on to www.ibn.a-star.edu.sg.

Quantum dots: Nano-probes of the future

IBN has pioneered methods to enable these nanocrystals to be used as powerful tools in bio-imaging and drug targeting

SINGAPORE– A team of researchers at the Institute of Bioengineering and Nanotechnology (IBN) has successfully addressed one of the biggest challenges facing the use of quantum dots in biomedical applications.
The group, led by IBN Executive Director Prof. Jackie Y. Ying, has invented methods that effectively give these unique materials water-soluble and non-toxic qualities, enabling them to be used as powerful fluorescent probes in biological labeling and diagnostics.
Quantum dots, also known as nano-crystals, are a special class of semiconductors that are extremely small in size (2-6 nanometers). These nanometer-sized particles are able to display any chosen color in the entire ultraviolet-visible spectrum through a simple change in their size or composition. They have shown great promise in wide-ranging applications, as solar cells and photodetectors.
More importantly, their strong and stable photoluminescent properties make them promising candidates for use in bio-imaging applications – they can emit different colors, based on pre-determined biological tags/signals. This means that scientists can attach quantum dots to a given protein or receptor to observe normal or abnormal cell functions. Unlike conventional organic dyes, quantum dots have enormous photostability, or the ability to fluoresce for several months. This allows them to track cell processes for longer periods of time and to shed more light on molecular interactions.
Nevertheless, the major disadvantages involving the use of quantum dots, particularly in biological applications, are their toxicity and insolubility (they would need to be soluble to be taken up by cells). Their surfaces would also need to be modified to enable the linking of bio-molecules. Previous efforts to tackle these problems involve synthetic methods that were too complicated or ineffective in maintaining the quantum dots’ stability or photoluminescent properties.
IBN scientists, however, have been able to pioneer a simple and efficient one-step procedure to render these quantum dots water-soluble and non-toxic (1).
According to Senior Research Scientist Dr. S. Tamil Selvan, IBN’s method of coating the particles with silica involves a simple water-in-oil reverse microemulsion procedure. The silica coating provides an effective non-toxic barrier and enables bio-molecules to adhere to the particles’ surface.
“This highly economical procedure produces robust and water-soluble quantum dots that have great potential to be used commercially in bio-imaging applications,” said Dr. Selvan.
The researchers have gone one step further by designing silica-coated composites of quantum dots and magnetic nanoparticles (2).
The hybrid composite is created easily and economically using reverse microemulsion synthesis. “Besides exhibiting the attractive qualities of water-soluble quantum dots, these nano-scale composites display magnetic properties, which are useful in magnetic cell separation, magnetic resonance imaging (MRI) contrast enhancement and magnetic transport of anti-cancer drugs,” said Dr. Dong Kee Yi, a Post-doctoral Fellow at IBN.
“Quantum dots pave the way for new methods of observing cellular processes in cells and small animals,” said Prof Ying. “It is hoped that this technology would allow for the precise diagnosis and treatment of diseases like cancer.” Different genetic markers of a tumor can be ‘color-coded’ with quantum dots, for instance, to enable the accurate identification, localization and treatment of cancer cells.
“IBN’s silica coating techniques are not limited to semiconductor quantum dots,” added Prof Ying. “They could also be used on a variety of hydrophobic materials such as metallic and magnetic particles, as demonstrated in our research.”
(1) S. T. Selvan, T. T. Tan, and J. Y. Ying, “Robust, Non-cytotoxic, Silica-Coated Quantum Dots for Biological Applications,” Advanced Materials, in press.
(2) D. K. Yi, S. T. Selvan, S. S. Lee, G. C. Papaefthymiou, D. Kundaliya, and J. Y. Ying, “Silica-coated Nanocomposites of Magnetic Nanoparticles and Quantum Dots,” Journal of the American Chemical Society, 127 (2005) 4990-4991.
About the Institute of Bioengineering and Nanotechnology (IBN)
The Institute of Bioengineering and Nanotechnology (IBN) is a member of the Agency for Science, Technology and Research (A*STAR). Established in March 2003, the Institute’s mission is to establish a broad knowledge base and conduct innovative research at the interface of bioengineering and nanotechnology. Positioned at the frontiers of engineering, IBN is focused on creating knowledge and cultivating talent to develop technology platforms that will spur the growth of new industries. IBN also fosters an exciting, multidisciplinary research environment for the training of students and young researchers to spearhead biomedical advancement in Singapore.
For more information on IBN, please log on to www.ibn.a-star.edu.sg.

Drug-loaded gels for targeted disease treatment and tissue regeneration
Hydrogels developed by IBN scientists can potentially make chemotherapy and tissue regeneration more convenient and safe
SINGAPORE– Scientists at the Institute of Bioengineering and Nanotechnology (IBN) have invented an injectable and biodegradable gel that can deliver drugs at targeted sites or act as a scaffold for tissue repair.This “hydrogel” is formed by simple injections at the desired site, where drugs or cells contained in the gel can be released at a controlled rate. No surgery is required, and the gel will degrade after the disease is treated or when the tissue has regenerated.IBN’s hydrogel is almost 90 percent composed of water. Another unique feature of the invention is the ease with which the hydrogel can be formed in the body without the need for surgery. Conventional hydrogels are normally manufactured in the labs before they are surgically implanted into a specific location in the body. IBN scientists, however, have devised a simple method of forming the hydrogel directly at the target site through the injection of two types of solution – a fluid drug-loaded biodegradable polymer and an enzyme which acts as the gelation catalyst.Previous efforts in this area have been unsuccessful at addressing a number of problems, including the conventional use of toxic catalysts and chemicals, which affect the bioactivity of the drugs and cells, causing tissue damage. IBN’s hydrogel, however, is formed using hyaluronic acid-tyramine conjugates with enzyme – both of which are non-toxic in nature.The chemically cross-linked hydrogel is also better than those produced using physical interactions, such as ionic and hydrophobic reactions, because it can retain its stability for a long time in the body. As this chemical cross-linkage can be achieved by an injected enzyme, this system does not need any harsh gelation trigger such as high temperature and toxic chemicals. In addition, IBN’s hydrogel is biodegradable. It does not need to be surgically removed after treatment, as it can decompose safely in the body.“Our hydrogel system can be effectively applied in cancer therapy, drug delivery and tissue engineering because it is convenient and safe, and it can deliver therapeutic proteins and cells without loss in their bioactivity,” said Dr Motoichi Kurisawa, the lead scientist of the project.“For example, in the area of tissue engineering, we can develop injectable hydrogel systems for bone and cartilage regeneration with the hydrogel acting as a scaffold and drug or cell delivery reservoir. In addition, this hydrogel is ideal for tissue regeneration as it offers a benign environment that is close to conditions in a body due to its high biocompatibility and water content,” said Dr Kurisawa.“For chemotherapeutic treatment, we can load the hydrogel with chemotherapeutics, which can be released only at the targeted malignant site, thus minimizing potential side effects on normal cells or tissues,” he added.This research was featured in a recent issue of Chemical Communications (1).(1) 1 M. Kurisawa, J. E. Chung, Y. Y. Yang, S. J. Gao and H. Uyama, “Injectable Biodegradable Hydrogels Composed of Hyaluronic Acid-Tyramine Conjugates for Drug Delivery and Tissue Engineering,” Chemical Communications, (2005) 4312-4314.The Institute of Bioengineering and Nanotechnology (IBN) is a member of the Agency for Science, Technology and Research (A*STAR), Singapore. Established in 2003, the Institute’s mission is to establish a broad knowledge base and conduct innovative research at the interface of bioengineering and nanotechnology. Positioned at the frontiers of engineering, IBN is focused on creating knowledge and cultivating talent to develop technology platforms that will spur the growth of new industries. IBN also fosters an exciting, multidisciplinary research environment for the training of students and young researchers to spearhead biomedical advancement in Singapore. For more information, please visit: www.ibn.a-star.edu.sg

Imitating Nature’s Scaffolding
Scientists at IBN have produced artificial fibers that act as ‘templates’ to grow new tissue

SINGAPORE – A team of researchers at the Institute of Bioengineering and Nanotechnology (IBN) has successfully created artificial fibers with nanometer-sized features that can be used to grow cells and tissue structures.These ‘fibrous scaffolds’ have been imbued with features of the natural extracellular matrix, the ground substance in which cells are embedded and a vital component in the engineering of human tissues.This research was recently published in the March issue of the leading journal Advanced Materials (1). The work on the “Three-Dimensional Reconstituted Extracellular Matrix Scaffolds for Tissue Engineering” also won an Outstanding Paper Award at the 12th International Conference on Biomedical Engineering in December 2005 (2).Scaffolds are ‘templates’ upon which the desired cell type or precursor is seeded for the growth of different tissues. Signaling molecules can also be incorporated into these structures to instruct or regulate cell growth and differentiation. Using IBN’s fibrous scaffolds, tissue engineers, for example, would be able to take a patient’s own cells, grow it into tissue in the lab, and subsequently implant the developed tissue back into the patient.While much work has been done to engineer suitable scaffolds, conventional production methods involve the use of high temperatures, organic solvents and/or a leaching step to develop porosity. Such conditions compromise the biological activity of proteins, and thus pose problems in the incorporation of biological molecules within the scaffolds.IBN, however, has been able to create fibers by interfacial polyelectrolyte complexation, which is a mild, aqueous-based process that takes place at ambient temperature. A method called ‘hydroentanglement’ that employs water pressure is then used to entangle the fibers into scaffolds. Previous work in this area was hampered by the tendency of the fibers to clump and form a dense monolith of low porosity. IBN scientists solved this problem by incorporating silica, an inorganic material that is found in simple marine organisms and some forms of glass, effectively crosslinking the fibers to obtain porous 3-D scaffolds. The porosity or permeability of the scaffold is important because a scaffold with a high surface-to-volume ratio provides for better interaction of cells with the matrix, and thus a better environment for the culture of various cell types for tissue engineering.Results have shown that cells could adhere and grow well on IBN’s fibrous scaffolds after they were incorporated with components such as collagen, fibronectin and cell-adhesion peptides. “We have created scaffolds based on natural polymers and extracellular matrix components that can be specially tailored for the adhesion and proliferation of a variety of cells,” said IBN Principal Research Scientist Dr Andrew Wan, who is the team leader of the project. “Hence, these scaffolds would have many potential applications in the engineering of tissues as implants, or as in vitro models for drug development“.A US patent has been filed on the invention.(1) A. C. A. Wan, B. C. U. Tai, K.-J. Leck, and J. Y. Ying, “Silica-Incorporated Polyelectrolyte-Complex Fibers as Tissue-Engineering Scaffolds,” Advanced Materials, 18 (2006), 641-644.(2) A. C. A. Wan, B. C. U. Tai, K.-J. Leck, S. Pek, S. Gao, and J. Y. Ying, “Three-Dimensional Reconstituted Extracellular Matrix Scaffolds for Tissue Engineering,” 12th International Conference on Biomedical Engineering, Singapore, December 2005. Outstanding Paper Award.A member of A*STAR’s Biomedical Sciences Institutes (Co. Reg. No. 199702109N)About the Institute of Bioengineering and Nanotechnology (IBN)The Institute of Bioengineering and Nanotechnology (IBN) is a member of the Agency for Science, Technology and Research (A*STAR). Established in March 2003, the Institute’s mission is to establish a broad knowledge base and conduct innovative research at the interface of bioengineering and nanotechnology. Positioned at the frontiers of engineering, IBN is focused on creating knowledge and cultivating talent to develop technology platforms that will spur the growth of new industries. IBN also fosters an exciting, multidisciplinary research environment for the training of students and young researchers to spearhead biomedical advancement in Singapore.For more information on IBN, please log on to www.ibn.a-star.edu.sg.
For queries, please contact:Adeline GohDID: +65 6824 7004 or HP: +65 9686 3160Email: agoh@ibn.a-star.edu.sgNidyah SaniDID: +65 6824 7005 or HP: +65 9762 9720Email: nidyah@ibn.a-star.edu.sg

Nanocarriers that can kill tumors with drugs and DNA
A breakthrough technology developed at IBN can potentially lead to more effective treatment methods for cancers
SINGAPORE– A team of scientists in Singapore has developed nanoparticles that can carry both small molecular anticancer drugs and nucleic acids simultaneously for improved cancer therapy. This groundbreaking work was published online in Nature Materials (1) on September 24, 2006, a leading materials science journal.The uniqueness of the new technology from the Institute of Bioengineering and Nanotechnology (IBN) lies in the design of a special biodegradable carrier (cationic core-shell nanoparticle), which can enclose drug molecules and allow therapeutic nucleic acids to bind onto it.It can efficiently introduce DNA into a cell to be incorporated into its genetic make-up, i.e. induce high gene expression level, especially in both human and mouse breast cancer cell lines, and mouse breast cancer model. The co-delivery of small molecular drugs with nucleic acids can improve gene transfection efficiency, reduce side-effects of these drugs, and achieve the synergistic effect of drug and gene therapy for the more effective treatment of cancer.Results have shown that the co-delivery of an anti-cancer drug (paclitaxel) with a highly potent anti-tumor ‘messenger molecule’ (IL-12 encoded plasmid (2) ) using the carrier suppressed cancer growth more efficiently than the delivery of either paclitaxel or the plasmid in mice bearing 4T1 breast cancer.In collaboration with Nanyang Technological University, experiments were also conducted to co-deliver paclitaxel and small interfering RNA (siRNA) targeting a protein that prevents cell death (Bcl-2) to MDA-MB-231 human breast cancer cell line. The cancer cells became more susceptible to the effects of the drug, due to the additional effect of the siRNA targeting Bcl-23.This special carrier can also be potentially used to co-deliver therapeutic nucleic acids to prevent cancer cells from developing resistance to multiple drugs4. This, coupled with the simultaneous delivery of specific anticancer drugs, could enhance the therapeutic effects of such drugs.Other scientists in this field have tried to use liposomes made from cationic (charged) lipids to transport drugs and DNA. The carrier developed at IBN is self-assembled from a biodegradable cationic copolymer. Hence, it is more easily produced and its size and characteristics are more easily controlled compared to liposomes. More importantly, it can deliver nucleic acids more effectively.“These nanocarriers developed by our team have a variety of applications in medication and as a gene transfection agent for biological research,” said Dr Yi-Yan Yang, who led the project team comprising Yong Wang, Shujun Gao, Wen-Hui Ye and Ho Sup Yoon. “They provide an interesting approach to improving the efficiency of cancer treatments.”United States and PCT (Patent Cooperation Treaty) patents have been filed by IBN on the invention.(1) Y. Wang, S. Gao, W.-H. Ye, H. S. Yoon and Y. Y. Yang, “Co-delivery of drugs and DNA from cationic core-shell nanoparticles self-assembled from a biodegradable copolymer,” Nature Materials, published online on September 24, 2006.Note: This paper was subsequently published in the October 2006 Vol 5 issue (pp 791-796) of Nature Materials.(2) IL-12 is a highly potent anti-tumor cytokine, and may also overcome paclitaxel-mediated T cell suppression.A member of A*STAR’s Biomedical Sciences Institutes (Co. Reg. No. 199702109N)(3) The suppression of the anti-apoptotic activity of Bcl-2 by the siRNA made the cells more sensitive to paclitaxel, leading to greater cytotoxicity of paclitaxel.(4) The therapeutic nucleic acid may be a vector encoding an antisense molecule directed against the P-glycoprotein mRNA in the target cell. Such a system can inhibit P-glycoprotein expression by the target, and hence, incapacitate its ability to establish multi-drug resistance, a common trait among cancer cells. This, together with the cytotoxic effects of the anti-cancer drug, should enhance the therapeutic effect of the system.About the Institute of Bioengineering and Nanotechnology (IBN)The Institute of Bioengineering and Nanotechnology (IBN) is a member of the Agency for Science, Technology and Research (A*STAR). Established in March 2003, the Institute’s mission is to establish a broad knowledge base and conduct innovative research at the interface of bioengineering and nanotechnology. Positioned at the frontiers of engineering, IBN is focused on creating knowledge and cultivating talent to develop technology platforms that will spur the growth of new industries. IBN also fosters an exciting, multidisciplinary research environment for the training of students and young researchers to spearhead biomedical advancement in Singapore.
please contact:Adeline GohDID: +65 6824 7004 or HP: +65 9686 3160Email: agoh@ibn.a-star.edu.sgNidyah SaniDID: +65 6824 7005 or HP: +65 9762 9720Email: nidyah@ibn.a-star.edu.sg

Gambling on consciousness
Gambling may provide a new window onto consciousness, according to a paper in the February issue of Nature Neuroscience. Assessing whether someone is aware of something is a notoriously difficult problem that is fundamental to investigating the basis of consciousness. This paper offers a new solution to this classic experimental dilemma by showing that people place bets only when they are aware of what they are betting on.Alan Cowey and colleagues asked participants to do several tasks in which performance is believed to occur without awareness for some of the time. For instance, when asked to classify letter strings into groups according to whether they obey a grammatical rule, participants who have seen examples of the rule in practice can perform at high levels while being unable to explain the rule. Similarly, patients with damage to the visual cortex can often make rudimentary visual judgments about stimuli that they deny seeing.Cowey and colleagues asked people to place a bet on whether or not their response was correct when they completed a trial of each of these tasks. They found that betting and task performance do not go hand in hand. Rather, participants place high bets on trials only when they are aware of the basis of their judgment – for example, when they recognize the rule governing their choices, or they consciously perceive the stimuli they are localizing. This method of measuring awareness is a significant advance over previous techniques because bets are placed without introspection about awareness, which can change what people consciously know.Author contact:Navindra Persaud (University of Oxford, UK)Tel: +44 7767 054 820; E-mail: navindra.persaud@univ.ox.ac.uk

For goodness sake
The detection of ‘agency’, the presence of an active participant in a situation, involves a brain region that is more active in altruistic people, reports a study in the February issue of Nature Neuroscience. Altruism, the tendency of people to help others without obvious benefit to themselves, remains a scientific puzzle.Scott Huettel and colleagues scanned the brains of people while they were either playing a simple computer game to earn money for charity or just watching the computer play the game by itself. Knowing that the computer is earning money for a good cause makes it easier to imagine an active intentional ‘mind’ behind that screen, apparently turning the game into a social situation involving altruistic behaviour. Figuring out social relationships generally involves activation of the posterior superior temporal sulcus (pSTS) on the right side of the brain. The authors indeed saw activity in this region specifically when participants were just watching the game.The authors also asked participants to answer questions designed to assess their tendency toward altruistic behavior, and found that the magnitude of pSTS activation strongly correlated with individual levels of altruism measured in response to these questions. Thus it seems that a specific brain response to a simulated altruistic situation may be directly related to a person’s real-life unselfish behavior.Author contact:Scott Huettel (Duke University, Durham, NC, USA)Tel: +1 919 681 9527; E-mail: scott.huettel@duke.edu

Nanocrystals used as dopants
Nanocrystals can mimic atoms in solid-state devices by altering the electrical properties — for example conductance — according to a report by Jeffrey Urban and colleagues in the February issue of Nature Materials.The researchers investigated the electrical properties of films obtained by the aggregation of PbTe and Ag2Te nanocrystals. When comparing the conductivity of films with different proportions of the two constituents, they found that when both types of crystals were present, the conductivity could be up to three orders of magnitude higher than in either of the single-component cases.Nanocrystal assemblies can be seen as materials in which the nanocrystals — which consist of thousands of atoms — act as the basic elements, with the advantage that the structure can be designed very precisely. The extension of the nanocrystal–atom analogy to the concept of doping (adding an impurity to alter the electrical properties) opens unexpected opportunities for the design of solid-state devices based on these aggregates, as it also allows very accurate control of the electrical properties.Author contact:Jeffrey J. Urban (IBM TJ Watson Research Center, Yorktown Heights, New York, USA)Tel: +1 914 945 1436; E-mail: urban@post.harvard.edu

Gene regulation: Non-coding RNA interferes with transcription
A non-coding RNA represses expression of a cell-cycle-regulated gene by directly interfering with the binding of transcription factors, a paper published online this week by Nature suggests. The discovery expands our knowledge of the diverse mechanisms used by non-coding RNAs in regulating gene expression.Transcription factors are known to bind to the promoter regions of genes and initiate the production of RNA transcripts. Alexandre Akoulitchev and colleagues find that a non-coding RNA – an RNA molecule that is not translated into protein – forms a complex with the major promoter region of the human dihydrofolate reductase (DHFR) gene, which in turn interferes with the binding of transcription factors. The non-coding RNA is only produced in quiescent cells, leading to repression of the DHFR gene in these conditions.Author contact:Alexandre Akoulitchev (University of Oxford, UK)Tel: +44 1865 275 614, E-mail: alexandre.akoulitchev@path.ox.ac.uk

Fetal Alcohol Syndrome: are cholesterol supplements the answer?
Each day in the United States, as many as 87 to 103 babies are born with alcohol related defects; annually, an estimated $75 million to $9.7 billion is spent on the care of these infants. The consumption of alcohol during pregnancy places the fetus at risk of developing FASD.
Cholesterol supplementation prevents fetal alcohol spectrum defects (FASD) in alcohol-exposed zebrafish embryos according to an article published online this week in Laboratory Investigation. The study from Yin-Xiong Li and colleagues details the mechanism and prevention of FASD and has implications for potential preventative prenatal intervention.Each day in the United States, as many as 87 to 103 babies are born with alcohol related defects; annually, an estimated $75 million to $9.7 billion is spent on the care of these infants. The consumption of alcohol during pregnancy places the fetus at risk of developing FASD, which include numerous abnormalities, such as neurological, craniofacial, and cardiac malformations. Using the zebrafish model, the authors found that alcohol interferes with embryonic development by disrupting cholesterol-dependent activation of a critical signaling molecule, called sonic hedgehog. They also showed that cholesterol supplementation of the alcohol-exposed embryos restored the functionality of the molecular pathway and prevented development of FASD-like defects.In addition, the authors report that FASD-like defects in zebrafish resulted from minimal fetal alcohol exposure, equivalent to a 55-kilogram woman drinking one 12-ounce beer. Their findings suggest that even small amounts of alcohol consumption may be unsafe for pregnant women and also indicate that cholesterol supplementation may be a potential means to prevent FASD.Author ContactYin-Xiong Li (Duke University Medical Center, Durham, NC, USA)Tel: +1 919 668 2310; Email: yinxiong.li@mc.duke.edu

Inhalant abuse: 'Sniffing' toluene for a high
Toluene, a commonly abused toxic compound, is shown to stimulate dopamine release in specific regions of the rat brain known as drug reward pathways, according to research published online in Neuropsychopharmacology this week. Until now it has been unclear whether toluene affects reward centers in the brain, and where, so ultimately this knowledge could help in developing strategies to prevent and treat addiction to substances containing toluene. Toluene is found in paint thinners, varnishes and even nail polish remover. Researchers demonstrate that toluene directly stimulates dopamine neurons causing dopamine release. Dopamine is a neurotransmitter and is released by reward centers in the brain causing a feeling of euphoria. The results suggest that the brain likely also interprets sniffing toluene as rewarding which can result in further abuse and possibly future use of other drugs.Besides showing where in the brain toluene acts, the researchers also demonstrate that, surprisingly, toluene substances are most effective when used at low concentrations. Since toluene is rapidly absorbed in the brain, this might explain why the preferred mode of delivery is by "huffing" or "sniffing". Sniffing is frequently considered a harmless recreational or party drug but unlike other drugs, even a single session of inhaling the compound can disrupt heart rhythms enough to cause cardiac arrest and lower oxygen levels enough to cause suffocation.Despite a decline in overall adolescent drug use since the late 90's, recreational use of inhalants is increasing. Inhalant abuse is now considered the fourth most abused drug among US teens according to NIDA. Because inhalants activate the same area of the brain that other drugs of abuse affect - such as cocaine and methamphetamines - future research will involve the investigation of their combined interactions on the brain.Author contact:Arthur C. Riegel (The Vollom Institute, Portland, OR, USA)Tel: +1 503 494 4723, E-mail: riegela@ohsu.eud PRESS CONTACTS…For media inquiries relating to editorial content/policy for the Journal Neuropsychopharmacology:Joyce-Rachel John (NPG Academic Journals, New York)Tel: +1 212 726 9214; E-mail: j.john@natureny.com For media inquiries relating to embargo policy for the Journal Neuropsychopharmacology:Ruth Francis (Nature London)Tel: +44 20 7843 4562; E-mail: r.francis@nature.com For media inquiries relating to the American College of Neuropsychopharmacology:Tel: +1 615 324 2360; E-mail: acnp@acnp.org