- 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...
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...
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...
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...
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).
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