Monday, 25 July 2011

Scavenger Cells Accomplices to Viruses

ScienceDaily (July 25, 2011) — Mucosal epithelia are well-protected against pathogenic germs. However, individual viruses, such as the HI virus, still manage to enter the body via the mucous membrane somehow. Cell biologists from the University of Zurich have now identified a new infection mechanism, demonstrating that the viruses use the body's own scavenger cells for the infection. The new findings are important for cancer-gene therapy and the development of anti-viral medication.

Mucosal epithelia do not have any receptors on the outer membrane for the absorption of viruses like hepatitis C, herpes, the adenovirus or polio, and are thus well-protected against pathogenic germs. However, certain viruses, such as the human immunodeficiency virus HIV, still manage to enter the body via the mucous membrane. Just how this infiltration occurs on a molecular level has been a mystery. Three hypotheses were discussed: firstly, that it's caused by mechanical damage to the mucous membrane; secondly, the presence of previously unknown receptors on the mucous membrane cells; and, thirdly, that the viruses are smuggled in via a kind of Trojan horse. Now, for the first time, cell biologists from the University of Zurich have succeeded in identifying the infection mechanism for adenoviruses.

In the recently published online magazine Nature Communications, Verena Lütschg and cell biologists from the Institute of Molecular Biology headed by Urs Greber reveal how type-5 adenoviruses in the lung epithelia utilize an immune response triggered by the infection for the progression of the infection: Adenoviruses use scavenger cells and their subsequent production of antiviral cytokines as a door-opener for the infection of the lung epithelial cells.

Exposure of shielded receptors

Antiviral cytokines play a key role in immunological reactions and trigger inflammatory responses, for instance. They induce the epithelial cells to expose certain receptors that are shielded under normal conditions and thus activate immune cells in defense. For healthy people, an infection of the lung with type-5 adenoviruses is harmless as they merely cause a cold. Under very stressful situations or in the case of chronic respiratory diseases, however, adenoviruses can cause severe, acute infections that can sometimes be fatal.

The recently identified infection mechanism can serve as a model for how the pathogens penetrate the mucosal epithelial cells and enter the body. However, it is also crucial from a therapeutic point of view. Type-5 adenoviruses are already used very often as transport vehicles in cancer-gene therapy today. Knowing the transport route will help develop both this gene therapy and specifically acting cancer treatment further.

Jou

ScienceDaily (July 24, 2011) — Microbiologists have uncovered a sneaky trick by the bacteriumPseudomonas aeruginosa to oust rivals. It deploys a toxin delivery machine to breach cell walls of competitors without hurting itself. Its means of attack helps it survive in the outside environment and may even help it cause infection.

P. aeruginosa is a common bacterium that lives in soil, and also an opportunistic pathogen best known for infecting the lungs of cystic fibrosis patients.

The scientists discovered that P. aeruginosa injects toxins into rival bacteria with a needle-like puncturing device called the type VI secretion system (T6SS). The toxins degrade competitors' protective barricades -- their cell walls. The research report also delineates the complex defensive mechanisms by which P. aeruginosa protects itself from its own artillery.

The journal Nature will publish the findings July 21.

While generally harmless to healthy people, this versatile bacterium takes advantage of those with weakened immune defenses, explained lead author Alistair Russell, a National Science Foundation fellow in the laboratory of Joseph Mougous, assistant professor of microbiology at the University of Washington (UW) and the study's senior author.

P. aeruginosa's ability to thrive in the thick airway mucous of cystic fibrosis patients and in burned or otherwise severely damaged skin makes it a major public health concern. All of these environments have one thing in common: other bacteria.

According to Russell, "Competition among bacteria is brutal and fierce." By killing off competitors, P. aeruginosa widens its territory, leading to its overall success. Moreover, the better able it is to outlast other bacteria in the environment, the better chance it has of coming in contact with, and colonizing, people.

"Pseudomonas is never going to encounter an infection site if it can't survive in the outside world," Russell added.

The researchers have detailed the mechanism of the T6SS, which breaches a protective layer present in bacteria and delivers toxic proteins that degrade the cell wall. After the cell wall is compromised, the cell bursts like an overfilled water balloon.

The T6SS mechanism transports toxins so that they never enter P. aeruginosa's cell wall space. To thwart an attack from other members of its species, each P. aeruginosa cell also has specific immunity proteins that inactivate toxins injected by neighboring cells.

Bacterial species that lack these immunity proteins are susceptible.

The study also confirms previous observations of the evolutionary similarity between the T6SS needlelike delivery mechanism and bacteriophage -- viruses that infect bacteria.

Interestingly, in a technique called "phage therapy," scientists have long sought to exploit the antibacterial properties of these viruses in order to treat bacterial infections.

One limitation is that bacteriophage are relatively unstable and require a host bacterium to increase their numbers. Mougous and his colleagues are excited by the potential of the antibacterial properties of the T6SS to be used in an analogous way.

Russell explained, "We might be able to take helpful bacteria, give them this system genetically, and increase their ability to clear out professional pathogens -- those bacteria that make their living causing disease."

Knowledge of this complex bacterial antimicrobial mechanism also might help in the design of more sophisticated drugs.

"If scientists could inhibit this secretion system in Pseudomonas through a new type of antibiotic, this opportunistic pathogen would not be able to break through the normal, healthy barrier of bacteria in the human body," Russell said.

The study was supported by the National Institutes of Health, the European Commission within the DIVINOCELL program, and a graduate research fellowship from the National Science Foundation.

In addition to Russell and Mougous, the study researchers were Rachel D. Hood and Michele LeRoux of the UW Department of Microbiology, (who contributed to the writing of this news item), and Nhat Khai Bui and Waldemar Vollmer of the Center for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University,

Alistair Russell at work in a microbiology research lab at the University of Washington, where he studies how Psuedomonas out-competes rival

Newcastle upon Tyne, U.K

Diamonds Pinpoint Start of Colliding Continents

ScienceDaily (July 22, 2011) — Jewelers abhor diamond impurities, but they are a bonanza for scientists. Safely encased in the super-hard diamond, impurities are unaltered, ancient minerals that can tell the story of Earth's distant past. Researchers analyzed data from the literature of over 4,000 of these mineral inclusions to find that continents started the cycle of breaking apart, drifting, and colliding about 3 billion years ago. The research, published in the July 22, 2011, issue ofScience, pinpoints when this so-called Wilson cycle began.

Lead author Steven Shirey at the Carnegie Institution's Department of Terrestrial Magnetism explained: "The Wilson cycle is responsible for the growth of the Earth's continental crust, the continental structures we see today, the opening and closing of ocean basins through time, mountain building, and the distribution of ores and other materials in the crust. But when it all began has remained elusive until now. We used the impurities, or inclusions, contained in diamonds, because they are perfect time capsules from great depth beneath the continents. They provide age and chemical information for a span of more than 3.5 billion years that includes the evolution of the atmosphere, the growth of the continental crust, and the beginning of plate tectonics."

Coauthor and longtime colleague Stephen Richardson of the University of Cape Town added: "It is astonishing that we can use the smallest mineral grains that can be analyzed to reveal the origin of some of Earth's largest geological features."

The largest diamonds come from cratons, the most ancient formations within continental interiors that have deep mantle roots or keels around which younger continental material gathered. Cratons contain the oldest rocks on the planet, and their keels extend into the mantle more than 125 miles (200 km) where pressures are sufficiently high, but temperatures sufficiently low, for diamonds to form and be stored for billions of years. The diamonds arrived at the surface as accidental passengers during volcanic eruptions of deep magma that solidified into rocks called kimberlites. The inclusions in diamonds come in two major varieties: peridotitic and eclogitic. Peridotite is the most abundant rock type in the upper mantle, whereas eclogite is generally thought to be the remnant of oceanic crust recycled into the mantle by the subduction or sinking of tectonic plates.

Shirey and Richardson, using their own work with other coinvestigators published in more than 20 papers over a 25-year period, reviewed the data from more than 4,000 inclusions of silicate -- Earth's most abundant material -- and more than 100 inclusions of sulfide from five ancient continents. The most crucial aspects were to look at when the inclusions were encapsulated and the associated compositional trends. Compositions vary and depend on the geochemical processing that precursor components underwent before they were encapsulated.

Two systems used to date inclusions -- the rhenium-osmium and samarium-neodymium techniques -- were compared. Both rely on natural isotopes that decay at exceedingly slow but predictable rates -- around one disintegration every ten years on the scale of an inclusion -- making them excellent atomic clocks for determining absolute ages.

The researchers found that before 3.2 billion years ago, only diamonds with peridotitic compositions formed -- whereas subsequent to 3 billion years ago, eclogitic diamonds dominated. "The simplest explanation is that this change came from the initial subduction of one tectonic plate under the deep mantle keel of another as continents began to collide on a scale similar to that of the supercontinent cycle today. The sequence of underthrusting and collision led to the capture of eclogite in the subcontinental mantle keel along with the fluids that are needed to make diamonds." remarked Shirey. "This transition marks the onset of the Wilson cycle of plate tectonics," concluded Richardson.

.

Tuesday, 5 July 2011

Attention cheaters: bacterial police are coming

At least some bacteria can “police” cheaters in their midst, a study has found, although how they do so is unclear.

“Even simple organisms such as bacteria can evolve to suppress social cheaters,” said Indiana University Bloomington biologist Gregory Velicer, co-author of a report on the findings in the May 17 issue of the journal Proceedings of the National Academy of Sciences.

When environmental conditions are hospitable, Myxococcus xanthus takes a rod-shaped form (yellow), swarming, dividing, and competing with other cells for nutrients. When stressed, the bacterium becomes more social, collaborating with other cells to produce round spores (green) that can withstand stress. Image courtesy of Juergen Berger and Supriya Kadam

Velicer, with Ph.D. student Pauline Manhes, studiedMyxococcus xanthus, a predatory bacterium that swarms through soil, killing and eating other microbes by releasing toxic and digestive compounds.

Like many cooperative creatures, M. xanthus also comes together in hard times. When famine hits, a colony will gather itself together in an orchestrated process aimed at hunkering down in a state that can wait out the hard times, or moving its members to greener pastures. The catch: many members will have to die helping the others through this transition. The microbial equivalent of a lottery determines who dies, and who gets a new lease on life.

And there are cheaters—whole strains of bacteria that game the system of chemical signals governing the live-or-die process to boost their chances at a winning ticket, so to speak. Their gain, of course, comes at the expense of the “good citizens.”

Velicer and Manhes exposed an “honest” strain of M. xanthus to a “cheating” strain over many cycles of this process, called fruiting body development. They found that over time, the freeloaders became less and less successful—as long as they were prevented from improving their arsenal in an arms race that seems to go on continually between competing strains. The cheaters gradually found themselves with fewer and fewer of their members inducted into the surviving group, while more upstanding strains increasingly dominated that privileged order.

The scientists prevented the cheaters from adapting, or evolving, by killing them all at the end of each cycle using a targeted antibiotic. They would then re-intro-duce members from their original strain in the next cycle.

The experiment revealed that “honest” strains continually act and adapt to keep their unsavory kin in check, though their exact strategies for doing so remain a mystery, Velicer said. The honest individuals might produce some chemical that cripples the cheaters, he speculated.

The researchers also tried pitting two “honest” strains against each other, the only known difference between them being that one had evolved to handle the cheaters, and the other hadn’t. They found that the first group outcompeted the second, but only when cheaters were around—a confirmation that their new adaptations were specifically cheater-oriented, Velicer contends.

“Mechanisms that prevent, mitigate or eliminate social conflict among interacting individuals are required for cooperation or multicellularity to succeed,” Velicer said. “Policing is one such mechanism. This study shows that bacteria have the potential to evolve behaviors that eliminate fitness advantages derived from cheating within social groups.”

In an intriguing twist, he added, some populations descended from the “honest” ancestors became cheaters themselves, but of a new kind that could sometimes exploit both the cooperative ancestor and the non-evolving cheater.

The study may cast a shadow on recent proposals that cheaters might be used to thwart infections of bacteria that cooperate with each other to cause disease in humans, Velicer said. The basic idea of such proposals is to introduce cheaters that will disrupt the social cohesion of infecting bacterial populations. But just as bacteria readily evolve resistance to antibiotics, cooperative bacteria that infect humans or animals may evolve to beat the cheats, he warned.

Mostly-male book images may reduce girls’ science scores

cience

Part of the reason boys tend to outscore girls in science classes may be that most textbooks show predominantly male scientists’ images, a small exploratory study has found.

The study, on 81 young high-school students, saw the “gender gap” apparently reversed when youths were tested based on a text containing only female scientist images, investigators said. The gap returned in its usual form when male-only images were used—and vanished when the photos showed equal numbers of men and women scientists, researchers said.

Part of the reason boys tend to outscore girls in science classes may be that most textbooks show predominantly male scientists’ images, a small exploratory study has found. (Image courtesy Virginia Dept. of Ed.)

The investigators cautioned, based on the small sample size and other factors, that it’s unrealistic to expect it would be so easy to erase the gender gap in real life.

Nonetheless, the findings hint that “providing students with diverse role models within textbook images” may be an important step, the researchers wrote in reporting their results. The study, by Jessica J. Good of Rutgers University in New Jersey and colleagues, is published in the March-April issue of theJournal of Social Psychology.

Other researchers have proposed that society can wipe out the performance gap—which has already shrunken in recent years—by making stronger efforts to give both sexes similar resources and opportunities. A 2004 report by the U.S. Center for Education Statistics noted that the previous year, science scores for eighth-grade boys exceeded those for eighth-grade girls in 28 out of 34 countries surveyed.

In the study on textbook images, ninth- and tenth-grade students, 29 male and 52 female, were asked to read a three-page chemistry text with one photo per page. Students were randomly assigned one of three versions of the reading: one whose pictures showed all male scientists, another with only female scientists and one with equal numbers of scientists of both sexes. The text itself was the same in all cases.

The students, who had no prior formal chemistry training, were next directed to take a short test on the reading.

Girls did significantly better when using the text with women-only images, the investigators reported. Boys did better with the men-only images, though the difference here didn’t reach a statistically significant level. Overall, average scores were higher for girls than boys among all students who got the women-only version.

The common predominance of male-scientist images in textbooks is a case of what some readers would perceive as “stereotype threat,” a phenomenon first described by researchers at Stanford University in California in the mid-1990s, according to Good and colleagues.

Stereotype threat occurs when a test-taker is presented with, or freshly reminded of, a stereotype that reflects negatively on his or her abilities in the subject matter at hand. Studies have found that stereotype threats push down the test-taker’s score, in the same direction the stereotype would predict.

Thus a predominance of male-scientist images in the majority of science textbooks may reinforce popular notions that girls are worse at science, and then lead to results in line with those ideas, said Good and colleagues.

Stereotype threats have been found to affect minorities as well as females. And the new findings suggest stereotype threat might work both ways—hurting not only those disfavored by a common stereotype, but those favored as well. In particular, although the popular stereotype is that boys are the top performers in science, Good’s results hinted that boys’ scores, too, might suffer if they saw pictures that cut against the flattering stereotype.

A simple solution that presents itself, though it requires more research, would be “mixed-gender textbook images,” the researchers wrote. These “may represent a simple and cost-effective way to remedy the negative effects of stereotypic textbook images.”

They cautioned that notwithstanding the latest results, other studies have found that removing stereotype threats doesn’t completely eliminate performance gaps among different groups, though it helps.

How exactly stereotype-threat effects work is unknown, Good and colleagues said, although there is evidence that they operate largely subconsciously. Possible reasons may include anxiety or intrusive thoughts caused by the stereotype threat, they wrote. Another explanation may be that there is a subconscious tendency to conform to societal expectations.

“Research should investigate the influence of diverse role models presented in textbooks as a way of improving performance of multiple stereotyped groups, not just women,” the investigators concluded. “Although eliminating gender bias in textbooks will most likely not eradicate the gender gap in science interest and achievement, it will begin to chip away at an ever crumbling foundation.”
* * *

A step forward for space power

27 June 2011

US scientists have gained insights into how to improve polymer solar cells' stability in space to power shuttles.

Inorganic solar cells have been investigated as power sources for spacecraft, and they are efficient, but they are heavy, so are costly to launch. Because of this, the power gains are marginal.

Organic polymer solar cells are light and flexible, making them attractive for use in satellites. But, these cells would degrade when exposed to the x-ray radiation present in space, making them inefficient. The x-rays pass through the relatively transparent polymer layer, causing a loss in voltage in the device.

Yang Yang from the University of California, Los Angeles, and Roderick Devine from the Air Force Research Laboratory at Kirtland Air Force Base, New Mexico, have discovered that the interface between the photoactive polymer layer and the electrode of the cell is the key to the cell's reaction to x-rays.

Polymer solar cells are lightweight so can be transported to space at a fraction of the cost of inorganic cells that are being investigated as power sources for spacecraft

The team saw that a charge accumulating at the interface after radiation exposure was causing the loss of voltage and that by modifying the interface, they could lessen this accumulation and improve the cell's stability. They tested different electrode interfaces - Ca/Al, Al and LiF/Al compared to TiO₂:Cs/Al and ZnO/Al interfaces - and found that the metal-oxide/metal interfaces were less susceptible to radiation.

Jianyong Ouyang from the National University of Singapore, an expert in polymeric electronic materials and devices, is impressed by Yang's research. 'The work is practically significant in that it provides guidance for improving polymer solar cells,' he says.

'In the immediate future, we will continue to focus our efforts on the interface to gain a greater understanding and control of its properties,' concludes Yang.

Catherine Bacon

Mystery of how plutonium enters cells solved

27 June 2011

It's been known for years that once plutonium is ingested it remains in the body for a long time, but what no one knew was how the plutonium is absorbed. Now, US scientists have found a cellular uptake pathway for plutonium, confirming a previous hypothesis but with a caveat.

Mark Jensen at Argonne National Laboratory and colleagues showed that plutonium hijacks the machinery used to deliver iron to mammalian cells - the transport protein transferrin.

That's maybe not so surprising, says Sarah Heath, a chemist at the University of Manchester, UK, who moved on to working with plutonium after first working with iron. She says that the two metals can often react in the same way.

'The charge density of the two ions is very similar,' says Heath, and this means the ions behave similarly.

Jensen and colleagues were interested in separating plutonium ions and decided to investigate how living organisms differentiate between metal ions in such different ways to chemists. To do that they tried to trick transferrin receptor protein to bind plutonium containing transferrin, but though plutonium can replace iron in the complex, only one form of plutonium containing transferrin binds with the receptor.

Plutonium hitches a ride into cells on an iron transporting protein

'At this point we realized that our fundamental studies of metal ion recognition by this pair of proteins had important implications for the cellular uptake of plutonium,' says Jensen.

Usually transferrin (Tf) forms a complex with two iron ions, one sit at the N-terminal end of the protein and one at the C-terminal end. If both of these irons are replaced by plutonium, the transferrin is too distorted to be recognised by the transferrin receptor protein. Using synchrotron X-ray fluorescence microscopy, the team showed that this means the plutonium cannot be absorbed by cells.

It turns out that only transferrin with plutonium bound to the C-terminal end and iron bound to the N-terminal end is a good enough match to be carried into cells. So although plutonium can use an iron uptake system to infiltrate cells, it can only do so with the help of iron.

There are probably other pathways for plutonium uptake Jensen says. 'However,' he adds 'the great majority of plutonium that gets into the blood stream is bound to transferrin, and the largest fraction of iron-transferrin in human blood (Fe_NTf) is the precursor to the form of iron-plutonium-transferrin that can be taken up by cells. This suggests that the transferrin pathway is important even if it is not the only way plutonium can infiltrate cells.'

The team have shown various targets to block plutonium uptake, which could prevent the metal getting into cells and causing damage.

Laura Howes