An international team of academics, including Professor Marco Oggioni from the University of Leicester’s Department of Genetics, has studied how localized infections can turn into the dangerous systematic disease sepsis — and has identified for the first time through genetic evidence that a single bacteria could be the cause.The study, which has been published in the academic journal PLOS Pathogens, examined the events that lead to sepsis by Streptococcus pneumoniae (pneumococcus), a major human pathogen, in mice. They found that in most cases the bacteria causing sepsis was started by a single pneumococcal cell.The study was an interdisciplinary collaboration between the Departments of Genetics, Infection Immunity and Inflammation and Mathematics at the University of Leicester, Professor Richard Moxon at the University of Oxford and scientists from overseas including the University of Siena.Professor Oggioni said: “Our data in experimental infection models indicate that we do not need only strategies which target many bacteria when it is too late, but that early intervention schemes which prevent the one-single cell that starts the disease process might provide substantial benefit to the patient.”In this work we have for the first time provided genetic evidence for a single cell origin of bacterial invasive infection. The scenario was hypothesized over 50 years ago, but so far only phenotypic and statistical evidence could be obtained for this event.”Under normal circumstances, when different bacteria are used in models of experimental infection of hosts who have not previously encountered the same pathogen, the vast majority is destroyed rapidly by the host’s innate immune system.In the researcher’s model, a dose of one million bacteria is needed to induce systemic disease in about half of the hosts in the study.This is in stark contrast to a much lower number of bacteria thought to make up the starting “seed” that leads to the development of systemic infection — and the assumption is that there must be one or more “bottlenecks” in the development of the disease.To investigate these bottlenecks, the researchers injected mice with a mix of three different variants of S. pneumoniae. About half of the mice developed sepsis and in almost all cases the bacteria causing sepsis were derived from only one of the three variants used in the initial challenge.Using statistical analysis as well as direct DNA sequencing, the researchers could show that in most cases the bacterial population causing sepsis was started by a single pneumococcal cell.When the researchers looked closer at how the immune system resists most injected bacteria, they found that macrophages, a type of immune cell that can gobble up bacteria, and specifically macrophages in the spleen, are the main contributors to an efficient immune response to this pathogen.Their findings suggest that if bacteria survive this initial counter-attack, a single ‘founder’ bacterium multiplies and re-enters the bloodstream, where its descendants come under strong selective pressure that dynamically shapes the subsequent bacterial population — resulting in the sepsis.The data also suggests that the single bacterium leading to sepsis has no obvious characteristics that give it an advantage over the 999,999 others, but that random events determine which of the injected bacteria survives and multiplies to cause disease.It is believed that the findings, suggesting that the development of sepsis starting from a single founding cell which survives the immune system’s initial counter-attack in mice, could also potentially apply to human systemic infections.This information could prove vital to understanding sepsis, as the causes of the disease are still largely unknown to the scientific community.Dr Oggioni added: “Knowing that there is a moment when a single bacterial cell escapes “normal” immune surveillance at the beginning of each invasive infection is an important paradigm and essential information which, in our opinion, should lead to changes in therapeutic protocols in order to maximise success of treatment outcome.”Story Source:The above story is based on materials provided by University of Leicester. Note: Materials may be edited for content and length.Read more
Aug. 13, 2013 — Soaring numbers of honey bees died last winter, University of Strathclyde research has revealed.A survey, run by Strathclyde academics on behalf of the Scottish Beekeepers’ Association, indicated 31.3 per cent of managed honey bee colonies in Scotland failed to survive last winter — almost double the previous year’s loss rate of 15.9 per cent.Dr Alison Gray and Magnus Peterson, of Strathclyde’s Department of Mathematics and Statistics, warn the figures ought to be of major concern because bees play a pivotal role in crop pollination, agricultural yields and, therefore, food supply and prices.Last winter’s figures represent 156 colonies lost during the winter of 2012-13, out of a total of 498 colonies being managed by beekeepers taking part in the survey. Furthermore, 67 of the 117 beekeepers who provided useable data reported losing at least some of their colonies between 1 October 2012 and 1 April 2013.Dr Gray said: “This is an extremely high loss rate.”In fact, the loss rate last winter is the highest we have found since these surveys began in 2006 — and is similar to that over the winter of 2009-10, when we estimate that 30.9 per cent of colonies were lost.”Results from European colleagues conducting similar surveys show that the loss rate in Scotland is amongst the highest in Europe this year, while similarly high losses have been reported recently from England and Wales.”The results were based on responses to online and postal questionnaires from a random sample of 300 members of the Scottish Beekeepers’ Association, which is thought to represent most of the country’s estimated 1,300 beekeepers.Since the spring of 2008, Mr Peterson has also been collecting data twice a year, from a network of volunteers across Scotland, on wild honey bees — those not managed by beekeepers and which instead live in habitats such as hollow trees and the roofs of old buildings. Last winter, 11 out of 20 wild honey bee colonies known to be alive last September — and reported on this spring — are known to have died.Mr Peterson said: “The latest results indicate a low survival rate, of just 45 per cent, amongst feral colonies over this last winter. This is the worst winter survival rate amongst the feral colonies known to the volunteers since they started monitoring them five years ago.”Dr Gray told how bees face many challenges internationally. She said: “Honey bees worldwide are having to contend with habitat loss and reduction in variety of forage sources due to pressures of intensifying land use, increasing spread of new and old pests — caused by globalisation of trade in bees and bee products — as well as possible adverse effects of agricultural pesticides.”For bees in northern Europe, poor weather conditions — combined with these various other factors which impact adversely on bees — are certainly making beekeeping a challenge and survival difficult for honey bees generally.”The difficult weather conditions are a particular problem in Scotland, with severe winters followed by long cold wet springs being a problem, especially if it comes after a poor wet summer as in this last year.”In April, Rural Affairs Secretary Richard Lochhead announced the Scottish Government was making £200,000 available to help commercial bee farmers to restock and rebuild their colonies, which were devastated by prolonged winter weather conditions.Read more
June 9, 2013 — Blood vessels within a sensory area of the mammalian brain loop and connect in unexpected ways, a new map has revealed.The study, published June 9 in the early online edition of Nature Neuroscience, describes vascular architecture within a well-known region of the cerebral cortex and explores what that structure means for functional imaging of the brain and the onset of a kind of dementia.David Kleinfeld, professor of physics and neurobiology at the University of California, San Diego, and colleagues mapped blood vessels in an area of the mouse brain that receives sensory signals from the whiskers.The organization of neural cells in this brain region is well-understood, as was a pattern of blood vessels that plunge from the surface of the brain and return from the depths, but the network in between was uncharted. Yet these tiny arterioles and venules deliver oxygen and nutrients to energy-hungry brain cells and carry away wastes.The team traced this fine network by filling the vessels with a fluorescent gel. Then, using an automated system, developed by co-author Philbert Tsai, that removes thin layers of tissue with a laser while capturing a series of images to reconstructed the three-dimensional network of tiny vessels.The project focused on a region of the cerebral cortex in which the nerve cells are so well known that they can be traced to individual whiskers. These neurons cluster in “barrels,” one per whisker, a pattern of organization seen in other sensory areas as well.The scientists expected each whisker barrel to match up with its own blood supply, but that was not the case. The blood vessels don’t line up with the functional structure of the neurons they feed.”This was a surprise, because the blood vessels develop in tandem with neural tissue,” Kleinfeld said. Instead, microvessels beneath the surface loop and connect in patterns that don’t obviously correspond to the barrels.To search for patterns, they turned to a branch of mathematics called graph theory, which describes systems as interconnected nodes. Using this approach, no hidden subunits emerged, demonstrating that the mesh indeed forms a continous network they call the “angiome.”The vascular maps traced in this study raise a question of what we’re actually seeing in a widely used kind of brain imaging called functional MRI, which in one form measures brain activity by recording changes in oxygen levels in the blood. The idea is that activity will locally deplete oxygen. So they wiggled whiskers on individual mice and found that optical signals associated with depleted oxygen centered on the barrels, where electrical recordings confirmed neural activity. Thus brain mapping does not depend on a modular arrangement of blood vessels.The researchers also went a step further to calculate patterns of blood flow based on the diameters and connections of the vessels and asked how this would change if a feeder arteriole were blocked. …Read more
Apr. 30, 2013 — Cooperative behaviour is widely observed in nature, but there remains the possibility that so-called ‘cheaters’ can exploit the system, taking without giving, with uncertain consequences for the social unit as a whole. A new study has found that a yeast colony dominated by non-producers (‘cheaters’) is more likely to face extinction than one consisting entirely of producers (‘co-operators’).
The findings, published April 30 in the open access journal PLOS Biology by Alvaro Sanchez and Jeff Gore from the Massachusetts Institute of Technology, are the results of the first laboratory demonstration of a full evolutionary-ecological feedback loop in a social microbial population.
The researchers found that while a cooperative yeast colony that survives by breaking down sucrose into a communal supply of simple sugars can support a surprisingly high ratio of freeloaders — upwards of 90 per cent — a sudden shock to its environment is highly likely to result in catastrophe.
“One of the main things we were interested in was the idea that natural selection can have an effect on the ecology of a population, so that as a population is evolving, natural selection affects the ecological properties,” said Dr Sanchez.
The researchers studied a cooperative species, Saccharomyces cerevisiae or ‘baker’s yeast’, focusing on two strains: one which had the SUC2 gene that produces the enzyme invertase (the co-operators), and one lacking SUC2 (the cheaters) making it unable to produce this enzyme. Invertase breaks down sucrose in the environment to liberate glucose and fructose that can be used by all yeast cells in the colony.
“We were very surprised by the fact that the total population size for the mixed group (consisting of both co-operators and cheaters) was about the same at equilibrium as the total population size in the absence of cheaters (i.e. purely co-operators). We didn’t expect that,” Dr Sanchez explained. “If it weren’t for the fact that the co-operators and cheaters were labelled with different colours, it would have been very hard to tell whether the population contained any cheaters or not.”
This was the case when the environment was benign. But when those stable populations were suddenly exposed to a harsh environment, all of the pure co-operator populations survived, while just one of six mixed populations adapted to the fast deterioration in conditions, the researchers found.
Benjamin Allen, Assistant Professor of Mathematics at Emmanuel College and Martin A. Nowak, director of the Program for Evolutionary Dynamics at Harvard University, co-authored an accompanying Primer in PLOS Biology, “Cooperation and the Fate of Microbial Societies.”
“The experiments of Sanchez and Gore beautifully illustrate the central dilemma in the evolution of cooperation. The yeast society depends on cooperation, but if cooperation is plentiful, ‘cheaters’ can exploit the generosity of others. This leads to cycles of cooperation and exploitation,” said Dr Allen.
The researchers found that an eco-evolutionary feedback loop links changes in population size, and their effects, with changes in the frequency of specific genetic types in the population. During the competition for survival between co-operators and cheaters, they showed that if the population starts off with sufficient co-operators then the social properties of the yeast spiral towards a final equilibrium position that comprises a stable mixture of co-operators and cheaters. However, if the initial population density, or the initial proportion of co-operators, is too low, then not enough simple sugars are produced, and the colony dies out.Read more
May 30, 2013 — Researchers at the University of Southampton have taken a significant step in a project to unravel the secrets of the structure of our Universe.
Professor Kostas Skenderis, Chair in Mathematical Physics at the University, comments: “One of the main recent advances in theoretical physics is the holographic principle. According to this idea, our Universe may be thought of as a hologram and we would like to understand how to formulate the laws of physics for such a holographic Universe.”
A new paper released by Professor Skenderis and Dr Marco Caldarelli from the University of Southampton, Dr Joan Camps from the University of Cambridge and Dr Blaise Goutéraux from the Nordic Institute for Theoretical Physics, Sweden published in the Rapid Communication section of ‘Physical Review D’, makes connections between negatively curved space-time and flat space-time.
Space-time is usually understood to describe space existing in three dimensions, with time playing the role of a fourth dimension and all four coming together to form a continuum, or a state in which the four elements can’t be distinguished from each other.
Flat space-time and negative space-time describe an environment in which the Universe is non-compact, with space extending infinitely, forever in time, in any direction. The gravitational forces, such as the ones produced by a star, are best described by flat-space time. Negatively curved space-time describes a Universe filled with negative vacuum energy. The mathematics of holography is best understood for negatively curved space-times.
Professor Skenderis has developed a mathematic model which finds striking similarities between flat space-time and negatively curved space-time, with the latter however formulated in a negative number of dimensions, beyond our realm of physical perception.
He comments: “According to holography, at a fundamental level the universe has one less dimension than we perceive in everyday life and is governed by laws similar to electromagnetism. The idea is similar to that of ordinary holograms where a three-dimensional image is encoded in a two-dimensional surface, such as in the hologram on a credit card, but now it is the entire Universe that is encoded in such a fashion.
“Our research is ongoing, and we hope to find more connections between flat space-time, negatively curved space-time and holography. Traditional theories about how the Universe operates go some way individually to describing its very nature, but each fall short in different areas. It is our ultimate goal to find a new combined understanding of the Universe, which works across the board.”
The paper AdS/Ricci-flat correspondence and the Gregory-Laflamme instability specifically explains what is known as the Gregory Laflamme instability, where certain types of black hole break up into smaller black holes when disturbed — rather like a thin stream of water breaking into little droplets when you touch it with your finger. This black hole phenomenon has previously been shown to exist through computer simulations and this work provides a deeper theoretical explanation.
In October 2012, Professor Skenderis was named among 20 other prominent scientists around the world to receive an award from the New Frontiers in Astronomy and Cosmology international grant competition. He received $175,000 to explore the question, ‘Was there a beginning of time and space?”.
The detailed paper AdS/Ricci-flat correspondence and the Gregory-Laflamme instability can be found here:Read more