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....

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