Showing posts with label Weekly BioNews. Show all posts
Showing posts with label Weekly BioNews. Show all posts

Wednesday, 17 September 2008

Weekly BioNews 8 - 15 Sep 2008

Cryopreservation techniques bring hopes for women cancer victims and endangered species



September 10, 2008 09:39 AM


Emerging cryopreservation techniques are increasing hope of restoring fertility for women after diseases such as ovarian cancer that lead to destruction of reproductive tissue. The same techniques can also be used to maintain stocks of farm animals, and protect against extinction of endangered animal species by maintaining banks of ovarian tissue or even nascent embryos that can used to produce offspring at some point in the future.


Until now these clearly related fields of research concerning preservation of animal and human ovarian tissue have been largely separate, but are now coming together to reinforce each other, following a highly successful workshop on cryopreservation of ovarian tissue, organised by the European Science Foundation (ESF). The human and animals cryopreservation fields have much to teach each other, and progress in both is likely to be accelerated as a result of growing collaboration, according to the ESF workshop's convenor Claus Yding Andersen.


Both parties can learn from each other," said Andersen. "Experiments which cannot be performed in women can be done in animal species," he noted, pointing out that much of the progress in humans has come as a result of animal experiments. But it is in humans where most successful transplantations of frozen ovarian tissue after thawing have been carried out, and where greatest experience in the field has been gained. Therefore the ESF conference considered how this could be applied to conservation of endangered species. "The vast experience in women, with several children born as a result of transplantation of frozen/thawed ovarian tissue, can be applied in endangered species to know where to implant and how to obtain pregnancies," said Andersen. The techniques will also be valuable in agriculture, for preserving ovaries of farm animals in tissue banks with the potential for subsequent re-creation...






Color-coded bacteria can spot oil spills or leaky pipes and storage tanks



September 10, 2008 11:39 PM


Oil spills and other environmental pollution, including low level leaks from underground pipes and storage tanks, could be quickly and easily spotted in the future using colour coded bacteria, scientists heard today (Thursday 11 September 2008) at the Society for General Microbiology's Autumn meeting being held this week at Trinity College, Dublin.


"Because bacteria have simple single-celled bodies it is relatively easy to equip them with a sensor and a brightly coloured 'reporter protein' which shows up under a microscope, alerting us to different substances leaking into the soil or seawater from oil spills, agricultural chemicals or other pollutants," says Professor Jan Van der Meer from the University of Lausanne in Switzerland.


Scientists have successfully shown that living bacteria can be used as a much more environmentally friendly way of detecting pollution than the currently used chemical methods of working out what has happened. "Chemical methods are often cumbersome, require sophisticated equipment, costly reagents or nasty materials," says Professor Van der Meer. "In comparison, our sensing bacteria are very simple to maintain. Tests with the bacteria are therefore extremely easy to carry out and do not require noxious chemicals."


"Our own tests, and checks by other laboratories, have shown that pollution testing using bacteria is a remarkably robust technique and produces reliable results," says Professor Van der Meer. "The heart of our colour sensor system is the bacteria themselves. They reproduce themselves in a growth medium, which makes the whole set-up really cheap,"


The new technique has already been successfully tested during a research expedition at sea, when the scientists demonstrated that the bacteria could measure different chemicals seeping from oil into the water, showing up as the blue light of bioluminescence in a simple light recording device...







Researchers develop nano-sized 'cargo ships' to target and destroy tumors


September 11, 2008 11:19 PM


Scientists have developed nanometer-sized 'cargo ships' that can sail throughout the body via the bloodstream without immediate detection from the body's immune radar system and ferry their cargo of anti-cancer drugs and markers into tumors that might otherwise go untreated or undetected.


In a forthcoming issue of the Germany-based chemistry journal Angewandte Chemie, scientists at UC San Diego, UC Santa Barbara and MIT report that their nano-cargo-ship system integrates therapeutic and diagnostic functions into a single device that avoids rapid removal by the body's natural immune system. Their paper is now accessible in an early online version at:



"The idea involves encapsulating imaging agents and drugs into a protective 'mother ship' that evades the natural processes that normally would remove these payloads if they were unprotected," said Michael Sailor, a professor of chemistry and biochemistry at UCSD who headed the team of chemists, biologists and engineers that turned the fanciful concept into reality. "These mother ships are only 50 nanometers in diameter, or 1,000 times smaller than the diameter of a human hair, and are equipped with an array of molecules on their surfaces that enable them to find and penetrate tumor cells in the body."


These microscopic cargo ships could one day provide the means to more effectively deliver toxic anti-cancer drugs to tumors in high concentrations without negatively impacting other parts of the body...






TGen investigators devise faster, cheaper way of analyzing the human genome


September 15, 2008 01:23 AM


Investigators at the Translational Genomics Research Institute (TGen) today announced a faster and less expensive way for scientists to find which genes might affect human health.


Using bar-codes, not unlike what shoppers find in grocery stores, TGen researchers found a way to index portions of the nearly 3-billion-base human genetic code, making it easier for scientists to zero in on the regions most likely to show variations in genetic traits.


The findings were published today in the online version of the journal Nature Methods. The study will be published in print in the journal's October edition.


Dr. David Craig, associate director of TGen's Neurogenomics Division, said the new method should cost only one-tenth, or less, of the current cost of sequencing genes commonly done to analyze Single Nucleotide Polymorphisms (SNPs), and in performing Genome-Wide Association (GWA) studies.


"Our goal is to find the genetic basis of disease,'' said Craig, the study's lead author. "It (the new method) provides us a way to immediately use next-generation sequencing technology for studying hundreds to thousands of individuals.''


John Pearson, the head of TGen's Bioinformatics Research Unit, said the new method would allow scientists worldwide to more easily tune their sequencing experiments, and conduct their experiments with greater speed...






Biological selenium removal: The solution to pollution?


September 15, 2008 01:03 PM


Selenium has been referred to as an "essential toxin" due to the fact that it shows only a marginal line between the nutritious requirement and toxic effects upon exposure. The steep dose response curve due to bioaccumulation effects have lead to the characterization of selenium as a "time bomb" that can be fused by exceeding a narrow threshold concentration in ecosystems through anthropogenic activities. Ironically, an estimated 0.5 to 1 billion people worldwide suffer from selenium deficiency, whereas areas of toxicity can be separated from selenium deficient areas by only 20 km.


The microbiological treatment of selenium - so called "dissimilatory metal reduction" - could supersede this problem, as selenium-reducing microorganisms are highly selective for selenate, reducing it to insoluble, less-toxic elemental selenium that can potentially be recovered from the process.


A study funded by the European Union, published in the September-October issue of the Journal of Environmental Quality, demonstrates that the biological treatment is indeed efficient for selenate reduction, and substantial amounts of selenate are converted to methylated selenium species or nano-sized elemental selenium particles. The emission of nano-sized selenium particles is problematic, as these can become bioavailable by direct assimilation or reoxidize to selenite and selenate. Dimethlyselenide and dimethyldiselenide, two species with unknown ecotoxicological long-term effects, contributed substantially to selenium dissolved in the effluent. Their formation was induced by minor temperature changes during biological reduction, thus a careful process control might drastically increase removal success of existing biotreatment systems for selenium and is a prerequisite for successful removal in full scale applications...






DNA 'Tattoos' Link Adult, Daughter Stem Cells In Planarians



ScienceDaily (Sep. 13, 2008)


Unlike some parents, adult stem cells don't seem to mind when their daughters get a tattoo. In fact, they're willing to pass them along.


Using the molecular equivalent of a tattoo on DNA that adult stem cells (ASC) pass to their "daughter" cells in combination with gene expression profiles, University of Utah researchers have identified two early steps in adult stem cell differentiation—the process that determines whether cells will form muscle, neurons, skin, etc., in people and animals.


The U of U researchers, led by Alejandro Sanchez Alvarado, Ph.D., professor of neurobiology and anatomy, identified 259 genes that help defined the earliest steps in the differentiation of adult stem cells in planarians—tiny flatworms that have the uncanny ability to regenerate cells and may have much to teach about human stem cell biology.


The findings, reported in the Sept. 11 issue of Cell Stem Cell establish planarians as an excellent model for studying adult stem cells in a live animal, rather than a laboratory culture dish.


"This allows us to study an entire stem cell population in its own environment," said Sanchez Alvarado, also an investigator with the Howard Hughes Medical Institute and the study's senior author. "It's likely that what we learned here can be applied to our own stem cell biology."


Planarians share similar biology with humans in many ways. They also, for reasons unknown, regenerate cells unlike any other animal—an entirely new worm can form from just a fragment of another worm. Planarians constantly regenerate new cells to replace those that die naturally or from injury...






Photosynthesizing Bacteria With A Day-night Cycle Contain Rare Chromosome



ScienceDaily (Sep. 15, 2008)


Researchers sequencing the DNA of blue-green algae found a linear chromosome harboring genes important for producing biofuels. Simultaneously analyzing the complement of proteins revealed more genes on the linear and the typical circular chromosomes then they'd have found with DNA sequencing alone.


The team recently reported the cyanobacterium Cyanothece 51142's genome in the Proceedings of the National Academy of Sciences Early Edition. Overlaying protein data let the researchers pinpoint about 16 percent more genes than by DNA sequencing alone. The collaboration included a proteomics team from the Department of Energy's Pacific Northwest National Laboratory, a gene sequencing team from the Washington University Genome Sequencing Center, and researchers from Washington University, Saint Louis University, and Purdue University.


"This is the first time anything like this has been found in photosynthetic bacteria. It's extremely rare for bacteria to have a linear chromosome," said team leader Himadri Pakrasi from WUSTL. "Nearly 100 percent of them do not."


Cyanobacteria are unique among bacteria because they seem part plant-like and part microbe-like. They use the sun's energy to make sugar via photosynthesis like plants do. And like bacteria, Cyanothece 51142 has other key life-sustaining functions, such as doctoring atmospheric nitrogen so other species can use it. This so-called nitrogen fixation is performed by a handful of bacterial species in water and soil. Cyanothece also makes ethanol and hydrogen, activities that drew the attention of the DOE and others looking for new ways to make fuel...






Viruses Collectively Decide Bacterial Cell's Fate



ScienceDaily (Sep. 15, 2008)


A new study suggests that bacteria-infecting viruses – called phages – can make collective decisions about whether to kill host cells immediately after infection or enter a latent state to remain within the host cell.


The research, published in the September 15 issue of the Biophysical Journal, shows that when multiple viruses infect a cell, this increases the number of viral genomes and therefore the overall level of viral gene expression. Changes in viral gene expression can have a dramatic nonlinear effect on gene networks that control whether viruses burst out of the host cell or enter a latent state.


"What has confounded the virology community for quite some time is the observation that the cell fate of a bacteria infected by a single virus can be dramatically different than that infected by two viruses," said Joshua Weitz, an assistant professor in the School of Biology at the Georgia Institute of Technology. "Our study suggests that viruses can collectively decide whether or not to kill a host, and that individual viruses 'talk' to each other as a result of interactions between viral genomes and viral proteins they direct the infected host to produce."


To study viral infections, Weitz teamed with postdoctoral fellow Yuriy Mileyko, graduate student Richard Joh and Eberhard Voit, who is a professor in the Wallace H. Coulter Department of Biomedical Engineering, the David D. Flanagan Chair Georgia Research Alliance Eminent Scholar in Biological Systems and director of the new Integrative BioSystems Institute at Georgia Tech....






Purifying Parasites From Host Cells With Light


ScienceDaily (Sep. 16, 2008)


Researchers have developed a clever method to purify parasitic organisms from their host cells, which will allow for more detailed proteomic studies and a deeper insight into the biology of organisms that cause millions of cases of disease each year.


Many infectious pathogens, like those that cause Toxoplasmosis or Leishmaniases, have a complex life cycle alternating between free-living creature and cell-enclosed parasite. A thorough analysis of the proteins that help these organisms undergo this lifestyle change would be tremendously useful for drug or vaccine development; however, it's extremely difficult to separate the parasites from their host cell for detailed study.


As reported in the September Molecular & Cellular Proteomics, Toni Aebischer and colleagues worked around this problem by designing special fluorescent Leishmania mexicana (one of the many Leishmaniases parasites). They then passed infected cells through a machine that can separate cell components based on how much they glow. Using this approach, the researchers separated the Leishmania parasites with only about 2% contamination, far better than current methods...



Electron micrographs (left=low, right=high magnification) highlighting the purification of Leishmania parasites (dark shapes) from their host cells. (Credit: MCP)

Monday, 8 September 2008

Weekly BioNews 1 - 8 Sep 2008

Nature inspires new highly specific drugs and organic products

September 2, 2008 12:18 PM

The best place to seek novel compounds for pharmaceutical drugs, alternative energy sources, and a host of industrial applications, is within natural systems that have evolved over millions of years. Scientists now realise that the precise molecular arrangements within natural pathways in organisms have been highly tuned for specific processes and provide both compounds that can be exploited directly and vital information over how to synthesise new products by mimicking biochemical processes. The bright future for research and development around such natural products was discussed recently at a conference organised by the European Science Foundaton (ESF), and the European Cooperation in the field of Scientific and Technical Research (COST).

"We found that natural products provide invaluable leads for drug discovery and opportunities to explore chemical and biological pathways, both of which are essential to advancing the life sciences," said the conference chair K.C. Nicolaou from the Scripps Research Institute in the US. Some of the products discussed at the conference were ready for preclinical development, having shown great potential for treating a range of infectious and metabolic diseases as well as cancers.
Such products are creating excitement because they promise to combine more effective treatment with reduced side effects, as well exploiting clean non-toxic synthetic techniques. For example Maurizio Botta from the University of Sienna in Italy discussed the design, synthesis and biological evaluation of new compounds for tackling AIDS and HIV by inhibiting reverse transcriptase, the process by which this type of retrovirus virus hijacks the host cell's genetic machinery to replicate itself. Some of these compounds have already exhibited strong activity against the AIDS virus in the laboratory.

There were also a number of promising anti-bacterial agents presented at the conference, which is an important development given the growing resistance of some bacterial species to existing antibiotics and the growing problem posed by MRSA, the "super bug" that plagues many hospitals and nursing homes. Dionisios Vourloumis, research director at the state run Greek research centre NCSR Demokritos, explained how bacteria could be disabled by targeting the RNA binding molecules needed for their genes to be expressed....


New nano device detects immune system cell signaling

September 3, 2008 10:33 PM

Scientists have detected previously unnoticed chemical signals that individual cells in the immune system use to communicate with each other over short distances.

The signals the researchers detected originated in dendritic cells – the sentinels of the immune system that do the initial detection of microscopic invaders – and were received by nearby T-cells, which play a number of crucial roles in the immune system, including coordination of attacks on agents that cause disease or infection.

The chemical signals cells exchange when they come into contact have been studied extensively. But it has not been possible to detect chemical messages that travel between cells that are nearby but not in contact – called paracrine signals – because they are highly localized and they are produced in concentrations that have been below detection levels. A new technology, called a multi-trap nanophysiometer, was required to demonstrate the existence of non-contact signaling. This is one of the first microfluidic devices that has been applied successfully to the study of cell-to-cell signaling in the immune system.

A detailed description of the multi-trap nanophysiometer (MTN) and how it enabled the accidental discovery of paracrine signaling has been published online by the Lab on a Chip journal. The new device was developed by a team of researchers at the Vanderbilt Institute for Integrative Biosystems Research and Education headed by John P. Wikswo, the Gordon A. Cain University Professor at Vanderbilt.

"This is an important advance and potentially very useful technology," says co-author Derya Unutmaz, now an associate professor of microbiology at New York University's School of Medicine. "The ability to study the behavior of single cells may not be as critical if you are studying the heart or muscles, which are mostly formed by uniform cells, but it is crucial for understanding how the immune system functions. The wide surveillance of the body that it conducts requires extensive communication between dozens of different kinds of immune cells."
The reason for this is that the dendritic cells, T-cells and B-cells in the immune system, which tend to concentrate in the lymph nodes spread throughout the body, function as individual, unattached cells. If dendritic cells detect invaders in the body, they rapidly migrate to lymph nodes and have to find the appropriate T-cells to alert them. But how dendritic cells attract the right T-cells among millions of cells within the lymph nodes remains an immunological puzzle....

New Evidence On Folic Acid In Diet And Colon Cancer

ScienceDaily (Sep. 5, 2008)

Researchers in the United Kingdom and Texas are reporting a new, more detailed explanation for the link between low folate intake and an increased risk for colon cancer, the second leading cause of cancer death in the United States.

Their study reinforces the importance of folate in a healthy diet.

Susan Duthie and colleagues note that researchers have known for years that a deficiency of folate, one of the B vitamins commonly called folic acid, increases the risk of birth defects. As a result, manufacturers enrich some foods with folate....

DNA Shows That Last Woolly Mammoths Had North American Roots

ScienceDaily (Sep. 5, 2008)

In a surprising reversal of conventional wisdom, a DNA-based study has revealed that the last of the woolly mammoths—which lived between 40,000 and 4,000 years ago—had roots that were exclusively North American.

The research, which appears in the September issue of Current Biology, is expected to cause some controversy within the paleontological community.

"Scientists have always thought that because mammoths roamed such a huge territory—from Western Europe to Central North America—that North American woolly mammoths were a sideshow of no particular significance to the evolution of the species," said Hendrik Poinar, associate professor in the departments of Anthropology, and Pathology & Molecular Medicine at McMaster University.

Poinar and Regis Debruyne, a postdoctoral research fellow in Poinar's lab, spent the last three years collecting and sampling mammoths over much of their former range in Siberia and North America, extracting DNA and meticulously piecing together, comparing and overlapping hundreds of mammoth specimen using the second largest ancient DNA dataset available...

Atomic Structure Of The Mammalian 'Fatty Acid Factory' Determined

ScienceDaily (Sep. 8, 2008)

Mammalian fatty acid synthase is one of the most complex molecular synthetic machines in human cells. It is also a promising target for the development of anti-cancer and anti-obesity drugs and the treatment of metabolic disorders. Now researchers at ETH Zurich have determined the atomic structure of a mammalian fatty acid synthase.

Synthesis of fatty acids is a central cellular process that has been studied for many decades. Fatty acids are used in the cell as energy storage compounds, messenger molecules and building blocks for the cellular envelope. Until now, individual steps of this process have been investigated using isolated bacterial enzymes. However, in higher organisms – except plants – fatty acid synthesis is catalyzed by large multifunctional proteins where many individual enzymes are brought together to form a “molecular assembly line”.

The atomic structure is the result of many years of research

As recently described in the journal Science, researchers at ETH Zurich, supported by the National Centre of Excellence in Research (NCCR) in Structural Biology at the Swiss National Science Foundation, determined the high-resolution structure of a mammalian fatty acid synthase using data collected at the Swiss Light Source (SLS) of the Paul Scherrer Institute (PSI) in Switzerland. These results crown the efforts begun in 2001 to determine the detailed structures of fatty acid synthases in higher organisms by a relatively small group of scientists at ETH Zurich...


Aerosols in climate change

Date: 08/09/2008

A group of scientists affiliated with the International Geosphere-Biosphere Programme (IGBP) have proposed a new framework to account more accurately for the effects of aerosols on precipitation in climate models. Their work appears in the 5 September issue of Science magazine.

The increase in atmospheric concentrations of man-made aerosols-tiny particles suspended in the air-from such sources as transportation, industry, agriculture, and urban land use not only poses serious problems to human health, but also has an effect on weather and climate.

Recent studies suggest that increased aerosol loading may have changed the energy balance in the atmosphere and at the Earth's surface, and altered the global water cycle in ways that make the climate system more prone to precipitation extremes.

It appears that aerosol effects on clouds can induce large changes in precipitation patterns, which in turn may change not only regional water resources, but also may change the regional and global circulation systems that constitute the Earth's climate.

The proposed framework improves scientists' ability to simulate present and future climates by integrating, for the first time, the radiative and microphysical effects of aerosols on clouds. The radiative effects of aerosols on clouds mostly act to suppress precipitation, because they decrease the amount of solar radiation that reaches the land surface, and therefore cause less heat to be available for evaporating water and energising convective rain clouds. Microphysical effects of aerosols can slow down the conversion of cloud drops into raindrops, which shuts off precipitation from very shallow and short-lived clouds...

Superbugs use poisons against defences

Date: 08/09/2008
Colonies of hospital superbugs can make poisons similar to those found in rattlesnake venom to attack our bodies' natural defences, scientists heard today (Monday 8 September 2008) at the Society for General Microbiology's Autumn meeting being held this week at Trinity College, Dublin.The toxins are manufactured by communities of the hospital superbug Pseudomonas aeruginosa called biofilms, which are up to a thousand times more resistant to antibiotics than free-floating single bacterial cells.

"This is the first time that anyone has successfully proved that the way the bacteria grow - either as a biofilm, or living as individuals - affects the type of proteins they can secrete, and therefore how dangerous they can potentially be to our health," says Dr Martin Welch from the University of Cambridge, UK.

"Acute diseases caused by bacteria can advance at an astonishing rate and tests have associated these types of disease with free-floating bacteria. Such free-floating bugs often secrete tissue-damaging poisons and enzymes to break down our cells, contributing to the way the disease develops, so it is natural to blame them. By contrast, chronic or long-term infections seem to be associated with biofilms, which were thought to be much less aggressive," says Dr Welch.

The research team's findings are very important to the NHS, which spends millions of pounds every year fighting chronic long-term bacterial infections which are incredibly difficult to treat.

"For example, these chronic infections by bacteria are now the major cause of death and serious disability in cystic fibrosis patients - which is the most common lethal inherited disease in the UK and affects about 8,000 people," says Dr Welch.

In cystic fibrosis the gene defect means that people are very susceptible to a particular group of opportunistic bacteria including Pseudomonas aeruginosa, which is one of the three major hospital superbugs. Aggressive antibiotic treatment can usually control the infection in cystic fibrosis sufferers but eventually the strain becomes completely resistant to antibiotics, leading to respiratory failure and death, often while still in their thirties.

"We think that the bacteria in a cystic fibrosis sufferer's lungs are partly living in communities called biofilms, and although medical scientists have investigated their strongly antibiotic-resistant properties, very little research has been done to investigate any active contribution the biofilms might have in causing diseases in the first place," says Dr Welch....

The robustness of metabolic networks

Date: 05/09/2008

Biological systems are constantly evolving in ways that increase their fitness for survival amidst environmental fluctuations and internal errors. Now, in a study of cell metabolism, a Northwestern University research team has found new evidence that evolution has produced cell metabolisms that are especially well suited to handle potentially harmful changes like gene deletions and mutations.The results, published online this week in the journal PNAS, could be useful in areas where researchers want to manipulate metabolic network structure, such as in bioengineering and medicine, and in the design of robust synthetic networks for use in energy production and distribution networks and in critical infrastructures, such as transportation networks.

The research was led by Julio M. Ottino, dean of the McCormick School of Engineering and Applied Science and Walter P. Murphy Professor of Chemical and Biological Engineering. Other authors of the paper, titled "Cascading failure and robustness in metabolic networks," are Luis A. Nunes Amaral, associate professor of chemical and biological engineering, and lead author Ashley Smart, who recently received his doctoral degree from Northwestern and is now a postdoctoral fellow at the California Institute of Technology.

Cell metabolism is essentially a large network of reactions whose purpose is to convert nutrients into products and energy. Because the network is highly interconnected, it is possible for a single reaction failure (which may be precipitated by a gene deletion or mutation) to initiate a cascade that affects several other reactions in the system. This event could be likened to disturbing a small area of snow that may trigger a large avalanche or the failure of a single transmission line in an electric power grid that may cause a widespread blackout.

By measuring the size of these "cascade" events in simulated metabolic networks, the Northwestern researchers were able to develop a quantitative measure of metabolic robustness: the more robust the network, the less the probability that small disturbances produce large cascades.

They found that the likelihood of large failure cascades in a metabolic network is unusually small, compared to what they would expect from comparable, randomly structured networks.

In other words, these metabolic networks have evolved to be exceptionally robust, adopting organisational structures that help minimise the potentially harmful impacts of gene deletions and mutations. Ottino and his colleagues developed a mathematical model describing the cascading failure phenomenon as a percolation-like process.....

Gene regulation makes the human

By Rachel EhrenbergWeb edition : Thursday, September 4th, 2008

Text Size A stretch of non-coding DNA revs up genes during development

A human version of a stretch of DNA, when inserted into a mouse embryo, cranks up the activity of genes in the developing thumb (shown blue). But this activity was much lower with the chimp or rhesus macaque version of the same DNA sequence. The difference could point to the kinds of developmental changes that make us human.

Genes alone don’t make the man — after all, humans and chimps share roughly 98 percent of their DNA. But where, when and how much genes are turned on may be essential in setting people apart from other primates.

A stretch of human DNA inserted into mice embryos revs the activity of genes in the developing thumb, toe, forelimb and hind limb. But the chimp and rhesus macaque version of this same stretch of DNA spurs only faint activity in the developing limbs, reports a new study in the Sept. 5 Science.

The research supports the notion that changes in the regulation of genes— rather than changes in the genes themselves — were crucial evolutionary steps in the human ability to use fire, invent wheels and ponder existential questions, like what distinguishes people from our primate cousins....

Monday, 1 September 2008

Weekly BioNews 25 Aug - 1 Sep 2008

Nano-sized 'trojan horse' to aid nutrition

August 25, 2008 12:18 PM

Researchers from Monash University have designed a nano-sized "trojan horse" particle to ensure healing antioxidants can be better absorbed by the human body.

Dr Ken Ng and Dr Ian Larson from the University's Faculty of Pharmacy and Pharmaceutical Sciences have designed a nanoparticle, one thousandth the thickness of a human hair, that protects antioxidants from being destroyed in the gut and ensures a better chance of them being absorbed in the digestive tract.

Antioxidants are known to neutralise the harmful effect of free radicals and other reactive chemical species that are constantly generated by our body and are thought to promote better health.

Normally our body's own antioxidant defence is sufficient, but in high-risk individuals, such as those with a poor diet or those at risk of developing atherosclerosis, diabetes or Alzheimer's disease, a nutritional source of antioxidants is required.

Dr Larson said orally delivered antioxidants were easily destroyed by acids and enzymes in the human body, with only a small percentage of what is consumed actually being absorbed.

The solution is to design a tiny sponge-like chitosan biopolymeric nanoparticle as a protective vehicle for antioxidants. Chitosan is a natural substance found in crab shells.

"Antioxidants sit within this tiny trojan horse, protecting it from attack from digestive juices in the stomach," Dr Larson said.

"Once in the small intestine the nanoparticle gets sticky and bonds to the intestinal wall. It then leaks its contents directly into the intestinal cells, which allows them to be absorbed directly into the blood stream... "


Study: DNA barcoding in danger of 'ringing up' wrong species

August 26, 2008 01:08 AM

DNA barcoding is a movement to catalog all life on earth by a simple standardized genetic tag, similar to stores labeling products with unique barcodes. The effort promises foolproof food inspection, improved border security, and better defenses against disease-causing insects, among many other applications.

But the approach as currently practiced churns out some results as inaccurately as a supermarket checker scanning an apple and ringing it up as an orange, according to a new Brigham Young University study. It was funded by the National Science Foundation and published in the prestigious Proceedings of the National Academy of Sciences.

With the International Barcode of Life project seeking $150 million to build on the 400,000 species that have been "barcoded" to date, this worthy goal warrants more careful execution, the BYU team says.

"To have that kind of data is hugely valuable, and the list of applications is endless and spans all of biology," said study co-author Keith Crandall, professor and chair of the Department of Biology at BYU. "But it all hinges on building an accurate database. Our study is a cautionary tale – if we're going to do it, let's do it right."

Proponents of DNA barcoding seek to establish a short genetic sequence as a way of identifying species in addition to traditional approaches based on external physical features. Their aim is to create a giant library full of these sequences. Scientists foresee a future handheld device like a supermarket scanner – a machine that would sequence a DNA marker from an organism, then compare it with the known encyclopedia of life and spit out the species' name...

Caltech scientists create DNA tubes with programmable sizes for nanoscale manufacturing

August 30, 2008 11:34 AM

Scientists at the California Institute of Technology (Caltech) have developed a simple process for mass producing molecular tubes of identical--and precisely programmable--circumferences. The technological feat may allow the use of the molecular tubes in a number of nanotechnology applications.

The molecular tubes are composed of wound-up strands of DNA. DNA has been considered an ideal construction material for self-assembling molecular structures and devices because two complementary DNA strands can automatically recognize and bind with each other. DNA has been used to form rigid building blocks, known as tiles, and these tiles can further assemble into extended lattice structures, including tubes. However, it has been difficult to control the diameters of such tubes.

Peng Yin, a senior postdoctoral scholar in bioengineering and computer science at Caltech's Center for Biological Circuit Design, along with his colleagues has designed a series of flexible, single-stranded DNA molecules, called single-stranded DNA tiles. Each single-stranded tile is exactly 42 bases long and contains four modular binding sites. By pairing up the complementary binding sites, these single-stranded tiles bind with each other in a particular orientation like Lego pieces snapped together, forming a tube composed of parallel DNA helices.

The circumference of the resulting tube is determined by the number of different 42-base pieces used in its construction. For example, four pieces create a tube with a circumference of 12 billionths of a meter (or 12 nanometers); five pieces, a 15-nanometer-circumference tube; and six pieces, an 18-nanometer tube...


Engineers create bone that blends into tendons

August 30, 2008 11:34 AM

Engineers at Georgia Tech have used skin cells to create artificial bones that mimic the ability of natural bone to blend into other tissues such as tendons or ligaments. The artificial bones display a gradual change from bone to softer tissue rather than the sudden shift of previously developed artificial tissue, providing better integration with the body and allowing them to handle weight more successfully. The research appears in the August 26, 2008, edition of the Proceedings of the National Academy of Sciences.

"One of the biggest challenges in regenerative medicine is to have a graded continuous interface, because anatomically that's how the majority of tissues appear and there are studies that strongly suggest that the graded interface provides better integration and load transfer," said Andres Garcia, professor in the George W. Woodruff School of Mechanical Engineering at the Georgia Institute of Technology.

Garcia and former graduate student Jennifer Phillips, along with research technician Kellie Burns and their collaborators Joseph Le Doux and Robert Guldberg, were not only able to create artificial bone that melds into softer tissues, but were also able to implant the technology in vivo for several weeks.

They created the tissue by coating a three-dimensional polymer scaffold with a gene delivery vehicle that encodes a transcription factor known as Runx2. They generated a high concentration of Runx2 at one end of the scaffold and decreased that amount until they ended up with no transcription factor on the other end, resulting in a precisely controlled spatial gradient of Runx2. After that, they seeded skin fibroblasts uniformly onto the scaffold. The skin cells on the parts of the scaffold containing a high concentration of Runx2 turned into bone, while the skin cells on the scaffold end with no Runx2 turned into soft tissue. The result is an artificial bone that gradually turns into soft tissue, such as tendons or ligaments...


'Fingerprinting' Helps Make Great Grapes

ScienceDaily (Aug. 30, 2008)

At about this time next year, nearly all of the 2,800 wild, rare and domesticated grapes in a unique northern California genebank will have had their "genetic profile" or “fingerprint” taken. These fingerprints may help grape breeders pinpoint plants in the collection that have unusual traits--ones that might appeal to shoppers in tomorrow's supermarkets.

Other grapes might be ideal for scientists who are doing basic research.

That’s according to Agricultural Research Service (ARS) plant geneticist Mallikarjuna Aradhya. He's heading the grape fingerprinting venture.

The grape collection that Aradhya is fingerprinting encompasses vineyards and screened enclosures, called “screenhouses." It is part of what’s officially known as the ARS National Clonal Germplasm Repository for Tree Fruit and Nut Crops and Grapes, in Davis, Calif.

To glean a distinctive genetic fingerprint of each member of the collection, Aradhya uses pieces of genetic material--or DNA--known as microsatellite markers. Eight markers are all that are needed for a genetic fingerprint of more familiar grapes, like close relatives of those already used for making wine or raisins or for eating out-of-hand...

Treatment For Hearing Loss? Scientists Grow Hair Cells Involved in Hearing

ScienceDaily (Aug. 30, 2008)

Oregon Health & Science University scientists have successfully produced functional auditory hair cells in the cochlea of the mouse inner ear. The breakthrough suggests that a new therapy may be developed in the future to successfully treat hearing loss. The results of this research was recently published by the journal Nature.

“One approach to restore auditory function is to replace defective cells with healthy new cells,” said John Brigande, Ph.D., an assistant professor of otolaryngology at the Oregon Hearing Research Center in the OHSU School of Medicine. “Our work shows that it is possible to produce functional auditory hair cells in the mammalian cochlea.”

The researchers specifically focused on the tiny hair cells located in a portion of the ear’s cochlea called the organ of Corti. It has long been understood that as these hair cells die, hearing loss occurs. Throughout a person’s life, a certain number of these cells malfunction or die naturally leading to gradual hearing loss often witnessed in aging persons. Those who are exposed to loud noises for a prolonged period or suffer from certain diseases lose more sensory hair cells than average and therefore suffer from more pronounced hearing loss...

Life Under The Laser: Unique Technology Illuminates Microscopic Activity In Body's Chemical Messenger System

ScienceDaily (Aug. 31, 2008)

Researchers at The University of Nottingham have developed a unique technology that will allow scientists to look at microscopic activity within the body’s chemical messenger system for the very first time, live as it happens.

The cutting edge laser technology has helped to attract £1.3 million from the MRC (Medical Research Council) for a five-year project that will offer a new insight into the tiny world of activity taking place within single cells and could contribute to the design of new drugs to treat human diseases such as asthma and arthritis with fewer side effects.

The team, involving scientists from the University’s Schools of Biomedical Science (Professor Steve Hill and Dr Steve Briddon) and Pharmacy (Dr Barrie Kellam), is concentrating on a type of specialised docking site (receptor) on the surface of a cell that recognises and responds to a natural chemical within the body called adenosine.

These A3-adenosine receptors work within the body by binding with proteins to cause a response within cells and are found in very tiny and highly specialised area of a cell membrane called microdomains. Microdomains contain a collection of different molecules that are involved in telling the cell how to respond to drugs or hormones...

Diversity Among Parasitic Wasps Is Even Greater Than Suspected

ScienceDaily (Sep. 1, 2008)

A tiny wasp that lays its eggs under the skin of unwitting caterpillars belongs to one of the most diverse groups of insects on Earth. Now researchers report that its diversity is even higher than previously thought.

By combining ecological and genetic data with the painstaking detective work of taxonomy, the researchers have dramatically increased – nearly doubling – the estimated number of species reported of six very species-rich genera of parasitoid wasps.

The subfamily to which these wasps belong, Microgastrinae, gets its name from its tiny abdomen. The wasp itself is quite small, about the size of the lead at the tip of a pencil.

By looking at the physical characteristics (morphology) of more than 2,500 wasps, the taxonomists identified 171 provisional species of microgastrine braconid wasps. But a comparative sequence analysis of a piece of a specific gene, a technique called DNA barcoding, found that there were actually 313 provisional species.

All of the wasps were reared from caterpillars collected in Area de Conservación Guanacaste (ACG), a biological reserve in northwestern Costa Rica. A decades-long ecological inventory of the area conducted by University of Pennsylvania ecologists Daniel Janzen and Winnie Hallwachs revealed that the wasps are extraordinarily specific to the caterpillar hosts they attack...


ATP-binding cassette transporter expression

Date: 27/08/2008

ABC-transporters expressed on endothelial cell membranes efflux anti-HIV drugs Researchers at Tulane University Medical Center in New Orleans (USA) have discovered that drug-efflux pumps, belonging to the ATP-binding cassette (ABC) transporter family, are constitutively expressed on vascular endothelial cells. Transcripts for several different ABC-transporters, e.g. MDR-1 (P-gp) and MRPs, were detected in endothelial cells, obtained from brain, aortic artery, pulmonary artery, dermal microvessels and umbilical veins. The ABC-transporter mediated efflux mechanisms decreased intracellular concentrations of the anti-HIV drugs, saquinavir, an HIV protease inhibitor (HPI) and zidovudine, a nucleoside reverse transcriptase inhibitor (NRTI), which are critical components of highly active antiretroviral therapy (HAART) against HIV. Inhibition of ABC-transporters, by using verapamil or MK-571, was shown to increase the intracellular retention of these anti-HIV agents. The MRP transporters were found to play a more dominant role in drug-efflux from endothelial cells. Pre-incubation of cells with the MRP-inhibitor, MK-571 significantly enhanced the intracellular levels of anti-HIV drugs. This study, entitled 'MRP (ABCC) transporters-mediated efflux of anti-HIV drugs, saquinavir and zidovudine, from human endothelial cells,' will be published in the September 2008 issue of Experimental Biology and Medicine.

These investigations led by Dr. Debasis Mondal, an assistant professor of Pharmacology, and co-authored by Mr. Mark Eilers and Dr. Upal Roy, demonstrated the significance of blocking MRP-transporters on endothelial barriers of blood vessels, in order to increase the pharmacokinetic efficacy of both HPIs and NRTIs. Drug-efflux pumps expressed on the blood-brain-barrier (BBB) were previously known to decrease drug entry into the central nervous system (CNS), however, this is the first evidence that endothelial cells from other organs express functional ABC-transporters, as well. The functional expression of MRPs on vascular endothelial barriers implicates their crucial role in facilitating the persistence of sub-endothelial HIV reservoirs....


Flu protein suppresses immune system

Date: 26/08/2008

Researchers at Rutgers University and The University of Texas at Austin have reported a discovery that could help scientists develop drugs to fight the much-feared bird flu and other virulent strains of influenza.The researchers have determined the three-dimensional structure of a site on an influenza A virus protein that binds to one of its human protein targets, thereby suppressing a person's natural defences to the infection and paving the way for the virus to replicate efficiently. This so-called NS1 virus protein is shared by all influenza A viruses isolated from humans - including avian influenza, or bird flu, and the 1918 pandemic influenza virus.

A paper detailing this breakthrough discovery appears in the PNAS (Proceedings of the National Academy of Sciences) Early Edition and will be published in an upcoming issue of the PNAS print edition.

About 10 years ago, Professor Robert M. Krug at The University of Texas at Austin discovered that the NS1 protein binds a human protein known as CPSF30, which is important for protecting human cells from flu infection. Once bound to NS1, the human protein can no longer generate molecules needed to suppress flu virus replication. Now, researchers led by Rutgers Professor Gaetano T. Montelione and Krug identified the novel NS1 binding pocket that grasps the human CPSF30 protein.

"Our work uncovers an Achilles heel of influenza A viruses that cause human epidemics and high mortality pandemics," said Montelione, professor of molecular biology and biochemistry. "We have identified the structure of a key target site for drugs that could be developed to effectively combat this disease."

X-ray crystallography, which was carried out by Kalyan Das, Eddy Arnold, LiChung Ma and Montelione, identified the three-dimensional structure of the NS1 binding pocket. "The X-ray crystal structure gives us unique insights into how the NS1 and human protein bind at the atomic level, and how that suppresses a crucial antiviral response," said Das, research professor at Rutgers.

Rei-Lin Kuo, Jesper Marklund, Karen Twu and Krug at The University of Texas at Austin verified the key role of this binding pocket in flu replication by genetically engineering a change to a single amino acid in the NS1 protein's binding pocket, which in turn eliminated the protein's ability to grasp the human protein that is needed to generate antiviral molecules. These investigators then produced a flu virus with an NS1 pocket mutation and showed that this mutated virus does not block host defences, and as a consequence has a greatly reduced ability to infect human cells...


Leptin aids Type-1 diabetics

Date: 26/08/2008

Terminally ill rodents with type 1 diabetes have been restored to full health with a single injection of a substance other than insulin by scientists at UT Southwestern Medical Center.Since the discovery of insulin in 1922, type 1 diabetes (insulin-dependent diabetes) in humans has been treated by injecting insulin to lower high blood sugar levels and prevent diabetic coma. New findings by UT Southwestern researchers, which appear online and in a future issue of the Proceedings of the National Academy of Sciences, suggest that insulin isn't the only agent that is effective. Leptin, a hormone produced by the body's fat cells, also lowers blood glucose levels and maintains them in a normal range for extended periods, they found.

"The fact that these animals don't die and are restored to normal health despite a total lack of insulin is hard for many researchers and clinicians to believe," said Dr. Roger Unger, professor of internal medicine and senior author of the study. "Many scientists, including us, thought it would be a waste of time to give leptin in the absence of insulin. We've been brainwashed into thinking that insulin is the only substance that can correct the consequences of insulin deficiency."

The mechanism of leptin's glucose-lowering action appears to involve the suppression of glucagon, a hormone produced by the pancreas that raises glucose levels. Normally, glucagon is released when the glucose, or sugar, level in the blood is low. In insulin deficiency, however, glucagon levels are inappropriately high and cause the liver to release excessive amounts of glucose into the bloodstream. This action is opposed by insulin, which tells the body's cells to remove sugar from the bloodstream.

In type 1 diabetes, which affects about 1 million people in the U.S., the pancreatic islet cells that produce insulin are destroyed. Type 1 diabetics must take insulin multiple times a day to metabolise blood glucose and regiment their diets. In comparison, patients with non-insulin dependent, or type 2, diabetes make insulin, but their bodies don't respond well to it. Type 2 diabetes affects between 18 million and 20 million people in this country....

Monday, 25 August 2008

Weekly BioNews 18 - 25 Aug 2008

- Synthetic moleculues could add spice to fight against cancer

August 20, 2008 08:13 PM

Turning up the heat on the red tomato during processing has the potential to give the popular garden staple added disease-fighting power, Ohio State University research suggests.

Scientists have found that lycopene molecules in tomatoes that are combined with fat and subjected to intense heat during processing are restructured in a way that appears to ease their transport into the bloodstream and tissue. The tomato is the primary food source of lycopene, a naturally occurring pigment linked to the prevention of cancer and other chronic diseases.

In its standard structure in the average red tomato, the lycopene molecule is laid out in a linear configuration. That structure seems to hinder the molecule's absorption through intestinal walls and into the blood, said Steven Schwartz, an investigator in Ohio State's Comprehensive Cancer Center and a professor of food science and technology at Ohio State.

Meanwhile, most of the lycopene that is found circulating in human blood is configured in a bent molecular form. This means that either the human body somehow transforms lycopene molecules through reactions that have yet to be identified, or that the bent molecular structures of lycopene are much more likely to be absorbed into the blood and transported to tissue – a necessary step in preventing disease.

Assuming the latter is true, Schwartz and colleagues have devised a way to process red tomatoes – the variety preferred by American consumers – into a sauce that contains bent molecular forms of lycopene. A clinical trial conducted in collaboration with Steven Clinton, a medical oncologist and physician scientist in Ohio State's Comprehensive Cancer Center, showed that people had more lycopene in their blood after eating the specially processed sauce than they did after eating regular red tomato sauce...


- Malaria Researchers Identify New Mosquito Virus

ScienceDaily (Aug. 22, 2008)

Researchers at the Johns Hopkins Bloomberg School of Public Health's Malaria Research Institute have identified a previously unknown virus that is infectious to Anopheles gambiae—the mosquito primarily responsible for transmitting malaria.

According to the researchers, the discovered virus could one day be used to pass on new genetic information to An. gambiae mosquitoes as part of a strategy to control malaria, which kills over one million people worldwide each year.

The virus, AgDNV, is a densonucleosis virus or "densovirus," which are common to mosquitoes and other insects, but do not infect vertebrate animals such as humans. Although the virus does not appear to harm the mosquitoes, the researchers determined it is highly infectious to mosquito larvae and is easily passed on to the adults.

According to Jason Rasgon, PhD, senior author of the study, the discovery came about serendipitously while the research team was conducting experiments to determine whether Wolbachia bacteria could be used to infect An. gambiae mosquito cells. During the analysis, Xiaoxia Ren, a postdoctoral fellow with Johns Hopkins Malaria Research Institute, noticed an "artifact," that appeared as a prominent band in the gel used to detect the bacteria...


PHOTO Anopheles gambiae mosquito infected with GFP-expressing AgDNV. (Credit: Johns Hopkins Bloomberg School of Public Health)


- How Daughter Is Different From Mother ... In Yeast Cells

ScienceDaily (Aug. 23, 2008)

The mother-daughter relationship can be difficult to understand. Why are the two so different? Now a Northwestern University study shows how this happens. In yeast cells, that is.

A research team has discovered a new mechanism for cell fate determination -- how one cell, the daughter, becomes dramatically different from the mother, even though they have the same genetic material. The study shows why mothers and daughters differ in how they express their genes.

By studying yeast, whose entire genome is known, scientists can learn the basics of cell division and apply that knowledge to the human system. Many of the fundamental mechanisms for cell division in yeast are conserved, or very similar, in mammals; many of the proteins involved in human disease are related to proteins that are involved in yeast cell division.

The new knowledge about cell fate determination could lead to a better understanding of healthy human cells, what goes awry in cancer cells and how human stem cells and germ cells work.

"Cancer may reflect a partial and aberrant loss of differentiated character, in which cells that were formerly specified to perform a specific task 'forget' that, and become more like the rapidly dividing stem cells from which they came," said Eric L. Weiss, assistant professor of biochemistry, molecular biology and cell biology in Northwestern's Weinberg College of Arts and Sciences. Weiss led the research team, which included scientists from the Massachusetts Institute of Technology...


PHOTO Yeast cells. (Credit: Image courtesy of Wikimedia Commons)

- Exploding Chromosomes Fuel Research About Evolution Of Genetic Storage

ScienceDaily (Aug. 24, 2008)

Human cells somehow squeeze two meters of double-stranded DNA into the space of a typical chromosome, a package 10,000 times smaller than the volume of genetic material it contains.

"It is like compacting your entire wardrobe into a shoebox," said Riccardo Levi-Setti, Professor Emeritus in Physics at the University of Chicago.

Now research into single-celled, aquatic algae called dinoflagellates is showing that these and related organisms may have evolved more than one way to achieve this feat of genetic packing. Even so, the evolution of chromosomes in dinoflagellates, humans and other mammals seem to share a common biochemical basis, according to a team Levi-Setti led. The team's findings appear online, in Science Direct's list of papers in press in the European Journal of Cell Biology.

Packing the whole length of DNA into tiny chromosomes is problematic because DNA carries a negative charge that, unless neutralized, prevents any attempt at folding and coiling due to electrostatic repulsion. The larger the quantity of DNA, the more negative charge must be neutralized along its length....


PHOTO This false-color image of the distribution of calcium in the chromosomes of a deer was obtained using secondary ion mass spectrometry with the University of Chicago's high-resolution scanning ion microprobe.The same technique applied to single-celled organisms called dinoflagellates are providing new insights into the evolution of chromosomes. (Credit: Courtesy of Riccardo Levi-Setti)


- Tiny Cellular Antennae Trigger Neural Stem Cells

ScienceDaily (Aug. 25, 2008)

Yale University scientists today reported evidence suggesting that the tiny cilia found on brain cells of mammals, thought to be vestiges of a primeval past, actually play a critical role in relaying molecular signals that spur creation of neurons in an area of the brain involved in mood, learning and memory.

The cilia found on brain cells of mammals until recently had been viewed as a mysterious remnant of a distant evolutionary past, when the tiny hair-like structures were used by single-celled organisms to navigate a primordial world.

“Many neuroscientists are shocked to learn that cells in the brain have cilia. Thus it was even more exciting to show that cilia have a key function in regulating the birth of new neurons in the brain,” said Matthew Sarkisian, post doctoral fellow in the department of neurobiology and co-first author on the study.

In the past decade, scientists have discovered primary cilia may have important functions in many animals. For instance, in 2000, Yale University scientists discovered defects in these cilia could lead to rare type of kidney disease. Researchers have been finding new functions for primary cilia ever since...

- Questioning sustainable biofuels

Date: 20/08/2008

With oil prices skyrocketing, the search is on for efficient and sustainable biofuels. Research published this month in Agronomy Journal examines one biofuel crop contender: corn stover.

Corn stover is made up of the leaves and stalks of corn plants that are left in the field after harvesting the edible corn grain. Corn stover could supply as much as 25% of the biofuel crop needed by 2030.

Scientists with the USDA-ARS Agroecosystem Unit located at the University of Nebraska examined the long-term sustainability of using corn stover as a biofuel crop.

When corn stover is not harvested as a biofuel crop, it can be left on the fields to restore vital nutrients to the soil. Full-scale harvesting of corn stover may deplete the soil.

Researchers measured the soil organic carbon levels and residue production over 14 years in fields planted continuously with corn, continuously with soybeans, and with a rotation of corn and soybeans. Organic carbon rates were found to stay steady or even increase in all three field types...



- Testing for West Nile virus

Date: 20/08/2008

A new test for West Nile virus in horses that could be modified for use on humans and wildlife may help track the spread of the disease, according to an article in the September issue of the Journal of Medical Microbiology.West Nile virus infects a wide range of animals, including humans, horses, dogs, cats, bats, squirrels, rabbits and birds. It is widely distributed in Africa, the Middle East and Europe. It was first reported in North America in 1999, when there were human fatalities in New York City. Since its arrival in the USA it has spread rapidly across the continent. The virus sometimes causes swelling of the brain, or encephalitis, which can be fatal. It is transmitted by several species of mosquito. Because the mosquitoes feed on so many different creatures the virus spreads quickly in areas where it has been introduced.

"Thousands of cases of West Nile virus have been reported worldwide, but 80% of infected people don't show any symptoms," said Dr Louis A Magnarelli, Director of The Connecticut Agricultural Experiment Station in the USA. "It is important to have highly sensitive and specific tests to diagnose infections and also to help track the ecology and epidemiology of West Nile encephalitis."

The US researchers have found that a new test designed to detect antibodies produced by horses is highly effective at diagnosing West Nile virus infections. Compared to the standard test for West Nile virus, the new test is much faster and gives accurate results. It was also useful in confirming past infections...

Wednesday, 20 August 2008

Weekly BioNews 12 - 18 Aug 2008

- Caltech engineers build mini drug-producing biofactories in yeast

August 16, 2008 08:58 PM

Researchers at the California Institute of Technology have developed a novel way to churn out large quantities of drugs, including antiplaque toothpaste additives, antibiotics, nicotine, and even morphine, using mini biofactories--in yeast.

A paper describing the research, now available online, will be featured as the cover article of the September issue of Nature Chemical Biology.

Christina D. Smolke, an assistant professor of chemical engineering at Caltech, along with graduate student Kristy Hawkins, genetically modified common baker's yeast (Saccharomyces cerevisiae) so that it contained the genes for several plant enzymes. The enzymes allow the yeast to produce a chemical called reticuline, which is a precursor for many different classes of benzylisoquinoline alkaloid (BIA) molecules. The BIA molecules are a large group of chemically intricate compounds, such as morphine, nicotine, and codeine, which are naturally produced by plants.

BIA molecules exhibit a wide variety of pharmacological activities, including antispasmodic effects, pain relief, and hair growth acceleration. Other BIAs have shown anticancer, antioxidant, antimalarial, and anti-HIV potential.

"There are estimated to be thousands of members in the BIA family, and having a source for obtaining large quantities of specific BIA molecules is critical to gaining access to the diverse functional activities provided by these molecules," says Smolke, whose lab focuses on using biology as a technology for the synthesis of new chemicals, materials, and products. However, the natural plant sources of BIAs accumulate only a small number of the molecules, usually "end products" like morphine and codeine that, while valuable, can't be turned into other compounds, thus limiting the availability of useful new products...
- MSU to create genomic clearinghouse for biofuel crops

August 16, 2008 08:58 PM

Michigan State University scientists, armed with a half-million-dollar federal grant, are creating an easily accessible, Web-based genomic database of information on crops that can be used to make ethanol.

"Ultimately this will allow us to create better biofuel crops," said C. Robin Buell, associate professor of plant biology and project leader. "Right now, about half of the biofuel crops don't have genomic databases, and the ones that do are in many different places and are annotated differently, which makes it difficult to compare and use the information."

Genomic databases contain information on the molecular biology and genetics of a particular species.

Buell and Kevin Childs, a postdoctoral researcher in her lab, will use the $540,000 joint grant from the departments of Agriculture and Energy to centralize the genomic databases, create uniform annotations (notes or descriptions of the genomes), provide data-mining and search tools, and provide a Web site for scientists from around the world to access the databases. They also will regularly update the information...

- Mount Sinai researchers discover technology that silences genes

August 18, 2008 12:10 PM

Mount Sinai researchers have developed a new gene silencing technology that could be used to target genes that can lead to the development of certain diseases. This technology could pave the way for preventing diseases where gene dysfunction plays a role. The groundbreaking research was led by Ming-Ming Zhou, Ph.D., Professor and Chairman of the Department of Structural and Chemical Biology at Mount Sinai School of Medicine. The findings, which will be published in the September issue of Nature Cell Biology, are available on the magazine's web site as of today.

"By being able to silence certain genes, we may be able to suppress genes that can cause diseases such as HIV/AIDS, cancer, inflammation and diseases of the central and peripheral nervous systems. We now know we can focus on these genes and potentially change the ultimate course of many diseases that have a major impact on people's lives," says Dr. Zhou...

- Maelstrom Quashes Jumping Genes

ScienceDaily (Aug. 18, 2008)

Scientists have known for decades that certain genes (called transposons) can jump around the genome in an individual cell. This activity can be dangerous, however, especially when it arises in cells that produce eggs and sperm. Such changes can threaten the offspring and the success of a species. To ensure the integrity of these cells, nature developed a mechanism to quash this genetic scrambling, but how it works has remained a mystery. Now a team of scientists, including researchers at the Carnegie Institution's Department of Embryology, has identified a key protein that suppresses jumping genes in mouse sperm and found that the protein is vital to sperm formation.

"There is a tiny cell component that is unique to germ cells—the precursors to egg and sperm—called nuage, which means 'cloud' in French. Other researchers recently suspected that nuage was involved in keeping genes from jumping around in germ cells of the female fruit fly," explained Carnegie's Alex Bortvin, a senior author of the study. "But until this mouse study, no one knew for sure if it was involved in mammalian germ cells. To test if the mouse nuage played a similar role in mammals, we focused on a mouse protein called Maelstrom whose distant relative protein in the fruit fly was implicated in the other study."

In this research, published in the August 12th issue of Developmental Cell, the scientists first looked at where the protein Maelstrom resides during the formation of sperm. By marking the protein with a fluorescent antibody, they found that it was predominantly located in the cytoplasm, near the nucleus of the germ cell, at the nuage. To understand what Maelstrom does during the formation of sperm, the scientists created mutant mice that did not have the gene to produce the Maelstrom protein...

Monday, 11 August 2008

Weekly BioNews 21 Jul - 12 Aug 2008

- Class of antibiotics can enhance gene-silencing tool

July 23, 2008 02:12 PM

A way to turn off one gene at a time has earned acceptance in biology laboratories over the last decade. Doctors envision the technique, called RNA interference, as a tool to treat a variety of diseases if it can be adapted to humans.

Emory University researchers have discovered that antibiotics known as fluoroquinolones can make RNA interference more effective in the laboratory and reduce potential side effects. The results will be published online this week in the journal Nature Biotechnology.

"The surprising aspect is that some fluoroquinolones have this previously unrecognized property," says senior author Peng Jin, PhD, assistant professor of human genetics at Emory University School of Medicine. "The good part is that doctors have years of experience treating bacterial infections with them, so they are generally considered safe."

The most powerful enhancer of RNA interference was enoxacin, which has been used to treat gonorrhea and urinary tract infections. The group of compounds also includes the widely used antibiotic ciprofloxacin. The antibiotics' effect on RNA interference appears to be chemically separate from their bacteria-killing activities.

Significant barriers still prevent RNA interference from working well in people, Jin says.
"The barriers include specificity and toxicity, as well as getting the RNA to the right place in the body," he says. "If we can enhance how potent a given amount of RNA is and reduce dosage, we're tackling both specificity and toxicity."

Some studies have found that side effects come from the amount of RNA injected, which can trigger an anti-viral response, rather than from the genetic sequence of the RNA used...
- Cellular Symmetry: What Cues Tell A Cell To Divide At The Center

ScienceDaily (Aug. 4, 2008)

Cells are intrinsically artistic. When the right signals tell a cell to divide, it usually splits down the middle, resulting in two identical daughter cells. (Stem cells are the exception to the rule.) This natural symmetry is visible on the macroscopic scale as well. All living creatures, be they mushrooms or humans, are visibly symmetric, a product of our cells’ preference for equilibrium.
Scientists at the MBL’s Whitman Center for Visiting Research are curious to know what cues tell a cell to divide at the center. Fred Chang, professor of microbiology at Columbia University, his postdoctoral student Nicolas Minc, and David Burgess, professor of biology at Boston College, are placing sea urchin eggs in snug, microscopic chambers shaped like triangles, squares, rectangles, stars, and ice cream cones to see whether the cell will still split 50-50...


- Australian Bird Research Could Rewrite 'Ring Theory' Of Speciation

ScienceDaily (Aug. 4, 2008)

New research has uncovered how different populations of the bird crimson rosella are related to each other – a discovery which has important implications for research into how climate change may affect Australia’s biodiversity.

Published in the journal Proceedings of the Royal Society B, the research investigates the genetic and geographical relationships between different forms of crimson rosellas and the possible ways that these forms may have arisen.

Dr. Gaynor Dolman of CSIRO’s Australian National Wildlife Collection says there are three main colour ‘forms’ of the crimson rosella – crimson, yellow and orange – which originated from the same ancestral population and are now distributed throughout south eastern Australia.
“Many evolutionary biologists have argued that the different forms of crimson rosellas arose, or speciated, through ‘ring speciation’,” she says...


- New Role Found For A 'Foxy Old Gene'

ScienceDaily (Aug. 5, 2008)

Researchers at the University of Pennsylvania School of Medicine have discovered that a protein called FOXA2 controls genes that maintain the proper level of bile in the liver. FOXA2 may become the focus for new therapies to treat diseases that involve the regulation of bile salts. The study was published online this week in Nature Medicine.

Bile, although made in the liver, is stored in the gall bladder and transported through ducts to the small intestine where it helps to digest fats from food. Bile salts, chemicals in bile that help digest fats and also keep cholesterol dissolved in the bile, are reabsorbed from the intestine and returned to the liver where they are broken up. The liver maintains a balance of bile salts by degrading old bile salts and synthesizing new ones. Problems arise when too many bile salts accumulate in the liver.

Diseases of bile regulation, such as primary sclerosing cholangitis (PSC), are characterized by problems with bile transport from the liver to the gut. The researchers found that in both children with biliary atresia and adults with PSC, syndromes of different etiologies, expression of FOXA2 in the liver is severely reduced. FOXA2 regulates expression of transporter proteins responsible for moving bile out of the liver, as well as several enzymes that function in bile acid detoxification. The study suggests that strategies to maintain FOXA2 expression might be a novel therapeutic goal...
- Research Exposes New Target For Malaria Drugs

ScienceDaily (Aug. 5, 2008)

The malaria parasite has waged a successful guerrilla war against the human immune system for eons, but a study in this week's Journal of Biological Chemistry has exposed one of the tricks malaria uses to hide from the immune proteins, which may aid in future drug development.

Malaria parasites (plasmodia) are transmitted to people via infected mosquitoes. Once inside their human hosts the parasites first set up shop in liver cells, then move into red blood cells (RBCs) to replicate and wait for the next mosquito to help continue the cycle.

After plasmodia infect a blood cell, they send out clusters of sticky proteins to the cell surface, enabling them to attach to blood vessels and escape destruction by the host's spleen while they replicate. This tactic can be especially problematic during pregnancy as malaria-infected RBCs congregate in the vessel-rich placenta (the source of food and oxygen for the growing fetus), creating health problems such as anemia, low birth-weight, fever and more.

Targeting these sticky proteins with drugs is difficult, however, as plasmodia contain many different varieties, which they use to evade the human immune system. However, certain parts of the protein have to remain constant for proper function, and in this study, Matthew Higgins generated high-resolution 3-D structures of a malarial sticky protein that binds to placenta, PfEMP1, to detail how plasmodia protect these conserved areas.

- Key to virulence protein discovered

Date: 05/08/2008

Researchers from the Virginia Bioinformatics Institute (VBI) at Virginia Tech have identified the region of a large family of virulence proteins in oomycete plant pathogens that enables the proteins to enter the cells of their hosts. The protein region contains the amino acid sequence motifs RXLR and dEER and has the ability to carry the virulence proteins across the membrane surrounding plant cells without any additional machinery from the pathogen. Once inside the plant cell, the proteins suppress the immune system of the plant allowing the infection to progress. The work, which focused on the virulence protein Avr1b from the soybean plant pathogen Phytophthora sojae, is published in the advance online edition of The Plant Cell.

Oomycetes are fungal-like organisms related to marine algae that cause tens of billions of dollars of losses to agriculture, forestry and natural ecosystems every year. The oomycete Phytophthora infestans caused the Irish potato famine in the nineteenth century. Another Phytophthora species, P. ramorum, is causing Sudden Oak Death disease in California's coastal forests. P. sojae results in $200-300 million in annual losses for commercial soybean farmers in the United States and estimated annual soybean losses of $1-2 billion worldwide. All of these oomycete species contain hundreds of genes that encode for virulence proteins that have the RXLR-dEER region.

The virulence proteins, including Avr1b, enter the soybean host where they are capable of suppressing an important process in plant immunity called programmed cell death. Programmed cell death is an in-built suicide mechanism that kills infected plant tissue, filling it with toxins so the pathogen can no longer feed on it. By preventing this protective mechanism in the host, the virulence proteins ensure that the pathogen can establish an unassailable foothold in the plant tissue from which the pathogen can pursue its destructive path.

Postdoctoral fellow Dr. Daolong Dou, the lead author of the article, commented: "We have suspected for a long time that these virulence proteins had some way of slipping inside plant cells to suppress immunity. Our findings finally nail down that mechanism and enable us to focus on how to block the entry mechanism."

The researchers also demonstrated that the RXLR and dEER motifs could be replaced by similar targeting sequences found in effector proteins produced by the malarial parasite Plasmodium. This hints that the targets of the effectors in the soybean and human hosts may be very ancient...
- Evolution Canyon reveals bacterial adaptation

Date: 28/07/2008

Bacteria living on opposite sides of a canyon have evolved to cope with different temperatures by altering the make-up of their 'skin', or cell membranes. Scientists have found that bacteria change these complex and important structures to adapt to different temperatures by looking at the appearance of the bacteria as well as their genes. The researchers hope their study, published in the August issue of Microbiology, will start a new trend in research.'Evolution Canyons' I and II are in Israel. They are similar, each with a hot south-facing slope and a cooler north-facing slope. The sun-exposed 'African' south-facing slopes get eight times more solar radiation than the shady, green, lush 'European' north-facing slopes. Scientists studied 131 strains of Bacillus simplex and found that bacteria on different slopes have evolved differently, forming different 'ecotypes' of the same species.

"We expected that 'ecotype' formation was linked to temperature but we had no initial clue of which specific cell attributes could have led to the adaptation," said Dr Johannes Sikorski from DSMZ in Germany. "To find out, we definitely had to study the appearance of the bacteria, not only their genes."

The cell membrane is one of the most important and complex parts of a cell. Membranes contain different fatty acid molecules; the branching type can change depending on temperature to keep the cell alive. The researchers found significant differences in the fatty acids of several ecotypes that live on different slopes in Evolution Canyon.

"Bacteria respond to temperature by altering their fatty acid composition in a constitutive, long-term fashion," said Dr Sikorski. We found that 'African' ecotypes from the hot slopes had more heat-tolerant fatty acids and 'European' ecotypes from the cool slopes had more cold-tolerant fatty acids in their membranes."

In most modern evolutionary studies, scientists rely on genetic data alone. Dr Sikorski and his colleagues focused on the result of the genetic changes instead: what the bacteria look like. "It is not a 'sexy' technique like genomics or proteomics but it gives a more comprehensive insight into the result of adaptation of the cell membrane," said Dr Sikorski...

- Disarming a possible biological weapon

Date: 28/07/2008

Scientists hope a vaccine is on the horizon for tularemia, a fatal disease caused by the pathogen Francisella tularensis, an organism of concern as a potential biological warfare agent. Until recently we knew very little about this bacterium. However, according to the August issue of the Journal of Medical Microbiology, research on the bacterium has been reinvigorated and rapid progress has been made in understanding how it causes disease.Infection with F. tularensis can result in a variety of symptoms, depending on the route of infection. For example, infection via an insect bite can lead to a swollen ulcer or fever, chills, malaise, headaches and a sore throat. When infection occurs by eating contaminated food, symptoms can range from mild diarrhoea to an acute fatal disease. If inhaled, F. tularensis infections can have a 30% mortality rate if left untreated.

"Only very few bacteria are needed to cause serious disease," said Prof Petra Oyston from Dstl, Porton Down. "Because of this and the fact that tularemia can be contracted by inhalation, Francisella tularensis has been designated a potential biological weapon. Since the events of September 2001 and the subsequent anthrax attacks on the USA, concern about the potential misuse of dangerous pathogens including F. tularensis has increased. As a result, more funding has been made available for research on these organisms and has accelerated progress on developing medical countermeasures."

Tularemia circulates in rodents and animals like rabbits and hares. Outbreaks in humans often happen at the same time as outbreaks in these animals. The disease is probably transmitted by insects like mosquitoes, ticks and deer flies. People can also become infected by contact with contaminated food or water and by breathing in particles containing the bacteria. Farmers, hunters, walkers and forest workers are most at risk of contracting tularemia.

There is currently no vaccine against tularemia. Because there are few natural cases of tularemia, money was not spent on the development of a vaccine. However, various nations developed F. tularensis as a biological weapon, including the reported production of antibiotic-resistant strains, so research into its pathogenesis has become a biodefence issue...
- Fuel from cellulose

August 10, 2008 07:09 PM

Independence from fossil fuel exporting nations, a reduction in the release of greenhouse gases, conservation of dwindling resources: there are any number of reasons to stop the use of fossil fuels. Hydrogen technology and solar energy will very probably provide the solution to our global energy problem—in the long term. For an initial quick remedy we may look to bioenergy. Biomass can be used to generate alternative carbon-based liquid fuels, allowing the continued use of current automotive combustion engine technology and existing infrastructure. At the same time, the chemical industry would continue to be supplied with the carbon compounds it requires as raw materials for plastics, textiles, etc. Mark Mascal and Edward B. Nikitin at the University of California, Davis (USA) have now developed an interesting new method for the direct conversion of cellulose into furan-based biofuels. As they report in the journal Angewandte Chemie, their simple, inexpensive process delivers furanic compounds in yields never achieved before.

Atmospheric carbon dioxide is viewed as the ultimate carbon source of the future. It is most efficiently "harvested" by plants via photosynthesis. Currently, biofuel producers primarily use starch, which is broken down to form sugars that are then fermented to give ethanol. Cellulose is however the most common form of photosynthetically fixed carbon. The problem is that the degradation of cellulose into its individual sugar components, which could then be fermented, is a slow and expensive process. "Another problem is that the carbon economy of glucose fermentation is poor," explains Mascal, "for every 10 g of ethanol produced, you also release 9.6 g CO2."

Could we avoid the breakdown of cellulose and fermentation? Mascal and Nikitin demonstrate that we can indeed. They have developed a simple process for the conversion of cellulose directly into "furanics", which are furan-based organic liquids. Furans are molecules whose basic unit is an aromatic ring made of one oxygen and four carbon atoms. The main product the researchers obtain under the conditions they have been developing is 5-chloromethylfurfural (CMF).

Opinions – Suggestions - Remarks