Ebola whole virus vaccine shown effective, safe in primates

 

An Ebola whole virus vaccine, constructed using a novel experimental platform, has been shown to effectively protect monkeys exposed to the often fatal virus.

The vaccine, described today (March 26, 2015) in the journal Science, was developed by a group led by Yoshihiro Kawaoka, a University of Wisconsin-Madison expert on avian influenza, Ebola and other viruses of medical importance. It differs from other Ebola vaccines because as an inactivated whole virus vaccine, it primes the host immune system with the full complement of Ebola viral proteins and genes, potentially conferring greater protection.
"In terms of efficacy, this affords excellent protection," explains Kawaoka, a professor of pathobiological sciences in the UW-Madison School of Veterinary Medicine and who also holds a faculty appointment at the University of Tokyo. "It is also a very safe vaccine."
The vaccine was constructed on an experimental platform first devised in 2008 by Peter Halfmann, a research scientist in Kawaoka's lab. The system allows researchers to safely work with the virus thanks to the deletion of a key gene known as VP30, which the Ebola virus uses to make a protein required for it to reproduce in host cells. Ebola virus has only eight genes and, like most viruses, depends on the molecular machinery of host cells to grow and become infectious.
By engineering monkey kidney cells to express the VP30 protein, the virus can be safely studied in the lab and be used as a basis for devising countermeasures like a whole virus vaccine. The vaccine reported by Kawaoka and his colleagues was additionally chemically inactivated using hydrogen peroxide, according to the new Science report.
Ebola first emerged in 1976 in Sudan and Zaire. The current outbreak in West Africa has so far claimed more than 10,000 lives. There are no proven treatments or vaccines, although several vaccine platforms have been devised in recent years, four of which recently advanced to the clinical trial stage in humans.
The new vaccine reported by Kawaoka has not been tested in people. However, the successful tests in nonhuman primates conducted at the National Institutes of Health (NIH) Rocky Mountain Laboratories, a biosafety level 4 facility in Hamilton, Montana, may prompt further tests and possibly clinical trials of the new vaccine. The work at Rocky Mountain Laboratories was conducted in collaboration with a group led by Heinz Feldmann of NIH.
Those studies were conducted with cynomolgus macaques, which are very susceptible to Ebola. "It's the best model," Kawaoka says. "If you get protection with this model, it's working."
Ebola vaccines currently in trials include:
-- A DNA-based plasmid vaccine that primes host cells with some of the Ebola proteins.
-- A vaccine based on a replication incompetent chimpanzee respiratory virus engineered to express a key Ebola protein.
-- A live attenuated virus from the same family of viruses that causes rabies, also engineered to express a critical Ebola protein.
-- A vaccine based on a vaccinia virus and engineered to express a critical Ebola protein.
Each of those strategies, Kawaoka notes, has drawbacks in terms of safety and delivery.
Whole virus vaccines have long been used to successfully prevent serious human diseases, including polio, influenza, hepatitis and human papillomavirus-mediated cervical cancer.
The advantage conferred by inactivated whole virus vaccines such as the one devised by Halfmann, Kawaoka and their colleagues is that they present the complete range of proteins and genetic material to the host immune system, which is then more likely to trigger a broader and more robust immune response.
Early attempts to devise an inactivated whole virus Ebola vaccine through irradiation and the preservative formalin failed to protect monkeys exposed to the Ebola virus and were abandoned.
Although the new vaccine has surpassed that hurdle, human trials are expensive and complex, costing millions of dollars.
The Ebola vaccine study conducted by Kawaoka was supported by the National Institutes of Health and by the Japanese Health and Labour Sciences Research Grants.

:The Source

http://www.sciencedaily.com 

Two degree Celsius climate change target 'utterly inadequate', expert argues

 

The official global target of a 2°C temperature rise is 'utterly inadequate' for protecting those at most risk from climate change, says a lead author on the Intergovernmental Panel on Climate Change (IPCC), writing a commentary in the open access journal Climate Change Responses.

The commentary presents a rare inside-view of a two-day discussion at the Lima Conference of the Parties (COP) on the likely consequences of accepting an average global warming target of 2°C versus 1.5°C (measured from pre-industrial times until 2100).
The discussions were part of the United Nations Framework Convention on Climate Change (UNFCCC) 'structured expert dialogue' in December 2014. They reveal unevenly distributed risks and political power differentials between high-income countries insisting on a 2°C target and low- and many middle-income countries pushing for 1.5°C or lower.
The 2°C target has been said to carry an increased risk of sea level rise, shifting rainfall patters and extreme weather events such as floods, droughts, and heat waves, particularly targeting the Polar Regions, high mountain areas, and the Tropics.
The author Petra Tschakert from The Pennsylvania State University and a coordinating lead author of the IPCC's Fifth Assessment Report says: "The consensus that transpired during this session was that a 2°C danger level seemed utterly inadequate given the already observed impacts on ecosystems, food, livelihoods, and sustainable development.
"A low temperature target is the best bet to prevent severe, pervasive, and potentially irreversible impacts while allowing ecosystems to adapt naturally, ensuring food production and security, and enabling economic development to proceed in a sustainable manner."
In her commentary, Tschakert explains that the target of keeping the global average temperature rise to below 2°C originates from early studies in the 1970s. This target became anchored in policy debates over the decades, and was officially sanctioned as the long-term global goal for greenhouse gas emission reductions at the COP15 in Copenhagen in 2009.
Despite support from high and upper middle-income countries with high emissions, the 2°C target has been subject to repeated criticism from climate scientists, economists, and political and social scientists.
Alliances representing over 70% of the parties around the table, including over 100 low- and middle-income countries and small island states, have repeatedly said that a 2°C rise is unsafe for their communities, and insist on a long-term goal to keep global average temperatures below 1.5°C. These states include the Pacific nation of Tuvalu that was recently hit by Cyclone Pam.
While the 2°C target is now being re-evaluated, no reference to an explicit 1.5°C target is included in the 2014 Lima Call for Climate Action, despite specific remarks on the lower temperature limit being made throughout the negotiations.
Having taken part in the latest structured expert dialogue in Lima, Peru, with country delegates to the COP, fellow IPCC authors and representatives from UN agencies and intergovernmental organizations, Tschakert now shares new insights into the ongoing debate on the adequacy of the long-term goal.
A representative of the World Health Organization at the session stressed that there was no 'safe limit' for health, as current impacts and risks from climate change were already unacceptable, impacting people's health significantly and inequitably. This includes a rise in undernutrition, food- and water-borne infections, and excess deaths during heat waves, of which 10,000 have already been attributed to the 2010 Russian heat wave.
In addition to heat waves, science participants in the dialogue said that extreme events such as floods and hurricanes were expected to cause high risk in a 2°C warmer world. These events would put at significant danger disadvantaged populations in megacities like Lagos, Mexico City or Shanghai, people whose livelihoods are dependent on natural resources, and those at risk from conflicts over scarce resources.
Tschakert says: "Using a figure for average global warming may indeed be the most convenient and compelling means to discuss the severity of climate change impacts, but not only does it inadequately capture the complexity of the climate system, it poorly reflects locally experienced temperature increases and the extreme and large variation across regions -- no single person or any species faces a global average."
Singapore highlighted that certain risks were already catastrophic for people and ecosystems in their region while only moderate in the aggregate. Along the same lines, Ethiopia re-emphasized the uneven distribution of risks for the African continent. Trinidad and St. Lucia stressed regional differences in risk from ice sheet loss and coral bleaching. Botswana raised the subject of costs for mitigation, adaptation, 'loss and damage' and technology transfer associated with both temperature targets.
In terms of ecosystems, it was said that limiting warming at 1.5°C could keep sea level rise below 1m, saving half of the world's corals, and leave some of the Arctic summer ice intact.
Tschakert says: "These implications emphasize what is truly at stake -- not a scientific bickering of what the most appropriate temperature target ought to be, but a commitment to protect the most vulnerable and at risk populations and ecosystems, as well as the willingness to pay for abatement and compensation. This should happen now, and not only when climate change hits the rich world."
The findings are timely as the long-term goal to stay below 2°C warming is currently undergoing a 2013-15 Review, the results of which are expected this June and could be adopted in Paris at COP21 in December 2015.
Tschakert concludes in her commentary: "The crux of the matter is no longer about the scientific validity of one temperature target over another... It is first and foremost about overcoming deeply entrenched divisions on value judgments, responsibility, and finance... It is about acknowledging that negative impacts of climate change under a 0.8°C temperature increase are already widespread, across the globe, and that danger, risk, and harm would be utterly unacceptable in a 2°C warmer world, largely for 'them' -- the mollusks, and coral reefs, and the poor and marginalized populations... even if this danger hasn't quite hit home yet for 'us'."

 :Story Source

http://www.sciencedaily.com

Sexual selection isn't the last word on bird plumage

 

In the world of bird fashion, the guys seem to have all the fun: brighter feathers, sharper accessories, more pizzazz.

Researchers going back to Charles Darwin have focused on the contrast between the sexes, attributing the males' brighter colors to their need to attract mates.
A group of researchers at University of Wisconsin-Milwaukee took a different approach, testing a hypothesis that evolution has actually resulted in similarities among the sexes as much as differences.
Looking at nearly 1,000 species of birds, they found that while males often have brighter feathers than females, the two sexes have come closer together in color over time to blend into their surroundings and hide from predators. Natural selection -- during migration, breeding in subtropical locales and care of young -- is as powerful as sexual selection.
"Although most studies of bird plumage focus on dichromatism, evolutionary change has most often led to similar, rather than different, plumage in males and females," the authors write.
Peter Dunn and Linda Whittingham, professors of behavioral ecology at UW-Milwaukee, wrote the paper with Jessica Armenta, a former UW-Milwaukee graduate student who now teaches at Austin Community College in Texas.
"Our study shows that ecology and behavior are driving the color of both sexes, and it is not due to sexual selection," they write.
The paper, "Natural and sexual selection act on different axes of variation in avian plumage color," is being published in Science Advances.
Armenta spent four years collecting data from 977 species of birds from six museums in the U.S. and Australia. She looked at six birds of each species, three males and three females.
Dunn and Whittingham analyzed the data, assigning each bird a color score based on scales of brightness and hue. They examined plumage color in relation to 10 measures of natural and sexual selection.
"Researchers have called for separate analyses of each sex for over a decade, but this is the first large-scale study to examine the color of each sex in relation to indices of both natural and sexual selection," they write.
When the sexes became more similar in color, they did so for reasons of natural selection. When the color gap increased, it had more to do with sexual selection, they found.
Dunn hopes the findings will send future research in new directions.
"A lot of research has focused on how plumage color is related to mating success, especially in males," he says, "so this should hopefully get researchers to think more about how color affects survival, especially predation and foraging success, in both sexes."
Within the larger findings is another surprise: male birds with multiple mates actually tend to be duller in color than their female counterparts.
Male red-winged blackbirds, for example, can have up to a dozen mates but are less colorful than their consorts.
"The reason for this is that males in these species often have a lot of black plumage," Dunn says.
 

:Story Source

 http://www.sciencedaily.com

High-fat diet alters behavior and produces signs of brain inflammation

High-fat diets have long been known to increase the risk for medical problems, including heart disease and stroke, but there is growing concern that diets high in fat might also increase the risk for depression and other psychiatric disorders.

A new study published in the current issue ofBiological Psychiatry raises the possibility that a high-fat diet produces changes in health and behavior, in part, by changing the mix of bacteria in the gut, also known as the gut microbiome.

The human microbiome consists of trillions of microorganisms, many of which reside in the intestinal tract. These microbiota are essential for normal physiological functioning. However, research has suggested that alterations in the microbiome may underlie the host's susceptibility to illness, including neuropsychiatric impairment.

This led researchers at Louisiana State University to test whether an obesity-related microbiome alters behavior and cognition even in the absence of obesity.

Non-obese adult mice were conventionally housed and maintained on a normal diet, but received a transplant of gut microbiota from donor mice that had been fed either a high-fat diet or control diet. The recipient mice were then evaluated for changes in behavior and cognition.

The animals who received the microbiota shaped by a high-fat diet showed multiple disruptions in behavior, including increased anxiety, impaired memory, and repetitive behaviors. Further, they showed many detrimental effects in the body, including increased intestinal permeability and markers of inflammation. Signs of inflammation in the brain were also evident and may have contributed to the behavioral changes.

"This paper suggests that high-fat diets impair brain health, in part, by disrupting the symbiotic relationship between humans and the microorganisms that occupy our gastrointestinal tracks," commented Dr. John Krystal, Editor of Biological Psychiatry.

Indeed, these findings provide evidence that diet-induced changes to the gut microbiome are sufficient to alter brain function even in the absence of obesity. This is consistent with prior research, which has established an association between numerous psychiatric conditions and gastrointestinal symptoms, but unfortunately, the mechanisms by which gut microbiota affect behavior are still not well understood.

Further research is necessary, but these findings suggest that the gut microbiome has the eventual potential to serve as a therapeutic target for neuropsychiatric disorders.

Story Source:

http://www.sciencedaily.com

Dark matter even darker than once thought

Astronomers using observations from the NASA/ESA Hubble Space Telescope and NASA's Chandra X-ray Observatory have studied how dark matter in clusters of galaxies behaves when the clusters collide. The results, published in the journal Science on 27 March 2015, show that dark matter interacts with itself even less than previously thought, and narrows down the options for what this mysterious substance might be.

Dark matter is a giant question mark looming over our knowledge of the Universe. There is more dark matter in the Universe than visible matter, but it is extremely elusive; it does not reflect, absorb or emit light, making it invisible. Because of this, it is only known to exist via its gravitational effects on the visible Universe (see e.g. heic1215a).

To learn more about this mysterious substance, researchers can study it in a way similar to experiments on visible matter -- by watching what happens when it bumps into things [1]. For this reason, researchers look at vast collections of galaxies, called galaxy clusters, where collisions involving dark matter happen naturally and where it exists in vast enough quantities to see the effects of collisions [2].

Galaxies are made of three main ingredients: stars, clouds of gas and dark matter. During collisions, the clouds of gas spread throughout the galaxies crash into each other and slow down or stop. The stars are much less affected by the drag from the gas [3] and, because of the huge gaps between them, do not have a slowing effect on each other -- though if two stars did collide the frictional forces would be huge.

"We know how gas and stars react to these cosmic crashes and where they emerge from the wreckage. Comparing how dark matter behaves can help us to narrow down what it actually is," explains David Harvey of the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, lead author of a new study.

Harvey and his team used data from the NASA/ESA Hubble Space Telescope and NASA's Chandra X-ray Observatory to study 72 large cluster collisions. The collisions happened at different times, and are seen from different angles -- some from the side, and others head-on [4].

The team found that, like the stars, the dark matter continued straight through the violent collisions without slowing down. However, unlike in the case of the stars, this is not because the dark matter is far away from other dark matter during the collisions. The leading theory is that dark matter is spread evenly throughout the galaxy clusters so dark matter particles frequently get very close to each other. The reason the dark matter doesn't slow down is because not only does it not interact with visible particles, it also interacts even less with other dark matter than previously thought.

"A previous study had seen similar behaviour in the Bullet Cluster," says team member Richard Massey of Durham University, UK. "But it's difficult to interpret what you're seeing if you have just one example. Each collision takes hundreds of millions of years, so in a human lifetime we only get to see one freeze-frame from a single camera angle. Now that we have studied so many more collisions, we can start to piece together the full movie and better understand what is going on."

By finding that dark matter interacts with itself even less than previously thought, the team have successfully narrowed down the properties of dark matter. Particle physics theorists have to keep looking, but they now have a smaller set of unknowns to work with when building their models[5].

Dark matter could potentially have rich and complex properties, and there are still several other types of interaction to study. These latest results rule out interactions that create a strong frictional force, causing dark matter to slow down during collisions. Other possible interactions could make dark matter particles bounce off each other like billiard balls, causing dark matter to be thrown out of collisions or for dark matter blobs to change shape. The team will be studying these next.

To further increase the number of collisions that can be studied, the team are also looking to study collisions involving individual galaxies, which are much more common.

"There are still several viable candidates for dark matter, so the game is not over, but we are getting nearer to an answer," concludes Harvey. "These 'Astronomically Large' particle colliders are finally letting us glimpse the dark world all around us but just out of reach."

Notes

[1] On Earth scientists use particle accelerators to find out more about the properties of different particles. Physicists can investigate what substances are made of by accelerating particles into a collision, and examining the properties and trajectory of the resulting debris.

[2] Clusters of galaxies are a swarm of galaxies permeated by a sea of hot X-ray emitting ionised hydrogen gas that is all embedded in a massive cloud of dark matter. It is the interactions of these, the most massive structures in the Universe that are observed to test dark matter's properties.

[3] The gas-gas interaction in cluster collisions is very strong, while the gas-star drag is weak. In a similar way to a soap bubble and a bullet in the wind where the bubble would interact a great deal more with the wind than the bullet.

[4] To find out where the dark matter was located in the cluster the researchers studied the light from galaxies behind the cluster whose light had been magnified and distorted by the mass in the cluster. Because they have a good idea of the visible mass in the cluster, the amount the light is distorted tells them how much dark matter there is in a region.

[5] A favoured theory is that dark matter might be constituted of "supersymmetric" particles. Supersymmetry is a theory in which all particles in our Standard Model -- electrons, protons, neutrons, and so on -- have a more massive "supersymmetric" partner. While there has been no experimental confirmation for supersymmetry as yet, the theory would solve a few of the gaps in our current thinking. One of supersymmetry's proposed particles would be stable, electrically neutral, and only interact weakly with the common particles of the Standard Model -- all the properties required to explain dark matter.

Story Source:

http://www.sciencedaily.com/