Tuesday, 28 February 2017
Vaccines are meant to pre-emptively protect the body from infection, and while it is possible to produce such protective immunity against the early liver stage of malaria infection, that has been a difficult goal to reach in places that are plagued by high rates of malaria infection. Publishing their work in Cell Reports, investigators at the University of Washington (UW) School of Medicine may have found an explanation. Malaria have a very complex life cycle, and the investigators found that the latter blood stage of malaria infection can inhibit the formation of protective immune cells, and their antibodies, that would otherwise prevent the early liver stage infection. "The blood stage of malaria infection has a very profound impact on the liver stage immune response, and that impact had never been dissected and visualized at this level," said one author of the work, Marion Pepper, a researcher at UW Medicine and Assistant Professor of Immunology at the UW School of Medicine. "These studies really suggest that you need a vaccine that is protective against both stages of infection to effectively prevent malaria."
To track how the blood stage of malaria infection overpowers the liver stage immune response, Pepper’s research team studied how malaria infection at the blood stage can overpower the immune response to the liver stage with a mouse model. Two groups of mice were infected with different forms of the malaria parasite, one of which was created by study collaborators in the lab of Stefan Kappe, UW Affiliate Professor of Global Health and investigator. This form arrested when it reaches the liver infection stage; the other form continues to develop into the blood infection stage. The researchers determined that six days following infection, mice with the blood stage infection had significantly lower antibodies levels compared to mice infected with the liver-stage parasite. The team wanted to know what was underlying that difference, so they observed Plasmodium liver stage-specific B cells differentiating - becoming a more mature or specialized cell type. B cells are able to differentiate into early effector cells, which secrete antibodies or long-lived memory cells, which can both confer protection against malaria. It was found that 14 days following infection, B cells in mice infected with blood stage malaria parasites did not follow through on the changes required for making rapidly responsive memory cells. But in mice that received the engineered, liver-stage parasite type, B cells could still differentiate, making the necessary memory cells and the antibodies that mount an effective immune response.
"This work really highlights the importance of looking at antigen-specific B cells," said Pepper. "These data also suggest that if you're getting a vaccine while you have an ongoing blood stage infection, there is a chance that the vaccine will not generate good memory cells because the blood stage disrupts all the processes that are involved in making that immunological memory."
The researchers are hopeful that this problem is solvable with the right drugs since they demonstrated that show that if the second stage of the infection is treated with a drug, B cells are then able to make responsive, effective memory cells. While that could still be some time off, this work may help answer questions about malaria vaccine efficacy in areas with high infection rates.
"Malaria has evolved with us throughout human existence and therefore has some potent immune evasion strategies. We really tried to tease apart some of the factors that could be driving the loss of protective immunity during natural infection and with current vaccine strategies in areas of high malaria transmission," explained Pepper. "Our next step is to compare malaria-specific B cells after vaccination or natural infection in humans so we can translate these findings and start to determine how to solve this problem."
Thursday, 9 February 2017
Antioxidants are believed to prevent some chronic illnesses - such as cardiovascular disease and cancer - due to their ability to protect against cell damage. New research suggests that a common antioxidant may also protect against non-alcoholic fatty liver disease.
Antioxidants are commonly found in fruits and vegetables, and they are thought to prevent cell damage. Vitamins C and E, selenium and carotenoids are all examples of antioxidants. Studies have shown that a diet rich in fruits and vegetables can help to prevent chronic diseases. However, it is not certain whether the antioxidants themselves protect against these diseases, or whether other substances in fruits and vegetables do. New research links one antioxidant in particular - commonly found in breast milk and foods such as kiwi, soy, and celery - to the risk of developing non-alcoholic fatty liver disease (NAFLD).
NAFLD is becoming increasingly widespread. In the United States, the disorder is the most common cause of liver disease, accounting for 75% of all chronic liver diseases.
Researchers from the University of Colorado Anschutz Medical Campus set out to examine whether an increased dose of pyrroloquinoline quinone (PQQ) administered prenatally in obese mice could halt the progression of NAFLD. The findings were published in the . Led by Karen Jonscher, Ph.D. - associate professor of anaesthesiology and a physicist at CU Anschutz - the team fed a high-fat, high-sugar Western diet to pregnant mice in order to induce obesity. Another group of pregnant mice was fed a healthful diet. Additionally, a subgroup from each of the two groups received PQQ in their drinking water.
The mice's offspring were also fed the two diets for 20 weeks, as well as having received PQQ through their mothers' breast milk, according to the group they were a part of.
As expected, the mice fed a Western diet gained more weight than those fed a healthful one. Supplemental PQQ, whether administered pre- or postnatally, had no impact on the weight gain. stress and pro-inflammatory genes in obese mice that had been given PQQ. This suggests that the antioxidant also reduced liver inflammation. Interestingly, these positive effects persevered in the offspring after the PQQ was withdrawn as part of the weaning process. "When given to obese mouse mothers during pregnancy and lactation, we found it protected their offspring from developing symptoms of liver fat and damage that leads to NAFLD in early adulthood," says Karen Jonscher. The researchers found decreased indicators of oxidative
PQQ is naturally found in soil, interstellar dust, and human breast milk. The antioxidant is critical for development in mammals, and it can also be found in a variety of plant foods, such as soy, parsley, celery, kiwi, and papaya. Jonscher also emphasizes the benefits of early PQQ diet supplementation for the prevention of liver disease. "Perhaps supplementing the diet of obese pregnant mothers with PQQ, which has proven safe in several human studies, will be a therapeutic target worthy of more study in the battle to reduce the risk of NAFLD in babies."
The author cautions, however, that pregnant women should always check with their physician before taking any supplements.
Monday, 6 February 2017
Scientists at the University of York have harnessed the therapeutic effects of carbon monoxide-releasing molecules to develop a new antibiotic which could be used to treat the sexually transmitted infection gonorrhoea. The infection, which is caused by the bacteria Neisseria gonorrhoeae, has developed a highly drug-resistant strain in recent years with new cases reported in the north of England and Japan. There are concerns that gonorrhoea, which is the second most common sexually transmitted infection in England, is becoming untreatable. Almost 35,000 cases were reported in England during 2014, with most cases affecting young men and women under the age of 25.
The interdisciplinary team, from the University of York's Departments of Biology and Chemistry, targeted the "engine room" of the bacteria using carbon monoxide-releasing molecules (CO-RMs). CO is produced naturally in the body, but there is increasing evidence that carbon monoxide enhances antibiotic action with huge potential for treating bacterial infections. The scientists found that Neisseria gonorrhoeae is more sensitive to CO-based toxicity than other model bacterial pathogens, and may serve as a viable candidate for antimicrobial therapy using CO-RMs. The CO molecule works by binding to the bacteria, preventing them from producing energy.
Scientists believe the breakthrough, published in the journal , could pave the way for new treatments. Professor Ian Fairlamb, from the University's Department of Chemistry, said: "The carbon monoxide molecule targets the engine room, stopping the bacteria from respiring. Gonorrhoea only has one enzyme that needs inhibiting and then it can't respire oxygen and it dies. "People will be well aware that CO is a toxic molecule but that is at high concentrations. Here we are using very low concentrations which we know the bacteria are sensitive to. "We are looking at a molecule that can be released in a safe and controlled way to where it is needed."
The team said the next stage is to develop a drug, either in the form of a pill or cream, so that the fundamental research findings can be translated on to future clinical trials. Professor Fairlamb added: "We think our study is an important breakthrough. It isn't the final drug yet but it is pretty close to it. People might perceive gonorrhoea as a trivial bacterial infection, but the disease is becoming more dangerous and resistant to antibiotics." He added: "Antimicrobial resistance is a massive global problem which isn't going away. We need to use many different approaches, and the development of new drugs using bioinorganic chemistry which is one crucial way we can tackle this problem, to control important bacterial pathogens before the current therapies stop working."
An international research team, led by the University of Bristol, has provided the first clues to understand how the mcr-1 gene protects bacteria from colistin - a 'last resort' antibiotic used to treat life-threatening bacterial infections that do not respond to other treatment options. Last year, members of the team, led by Dr Jim Spencer from the School of Cellular and Molecular Medicine, in collaboration with colleagues from Oxford, Cardiff, Diamond Light Source, Thailand and China, identified mcr-1 as the first colistin-resistance gene that could be passed between bacteria, enabling resistance to spread rapidly within a bacterial population.
Since then, the mcr-1 gene has been detected in common bacteria, such as E. coli, in China, the United States and across Europe first in farm animals and recently - worryingly - in human patients. The spread of mcr-1 has been linked to agricultural use of colistin, indicating that transmission between animals and humans may take place. In response to these findings the Chinese government has now banned use of colistin in animal feed. Colistin acts by binding to, and disrupting, the outer surface of bacteria. Bacteria carrying the mcr-1 gene make a protein that modifies the bacterial surface to reduce colistin binding, making the organism resistant.
In their work the team used X-rays produced at Diamond's crystallography beamlines to generate detailed pictures of the portion of this protein responsible for this modification, and with this information identified key features that are necessary for it to function. They also constructed computer models of the chemical reaction that leads to resistance. This provides the first clues as to how mcr-1 acts within the bacterial cell, as well as information essential to efforts to identify ways of blocking MCR-1 function that could restore the activity of colistin against bacteria carrying mcr-1. Professor Adrian Mulholland, co-author of the study and Principal Investigator for the Bristol Bridge initiative, based in the School of Chemistry, said: "The importance of understanding colistin resistance can hardly be overstated: it is rapidly emerging threat to public health. "Our results illuminate the structural and (for the first time) mechanistic basis of transferable colistin resistance conferred by mcr-1, thanks to the combination of biological, chemical and computational expertise brought to bear on this project.We are confident that our findings will drive efforts to understand mcr-1-mediated resistance and ultimately help identify routes towards overcoming MCR-1 activity in harmful bacteria."
A. Mulholland and J. Spencer et al, , doi:10.1038/srep39392
Wednesday, 25 January 2017
|The Red Plant "Mars" (Image: Pixabay)|
Microbes that rank among the best and most ancient organisms on Earth that may survive the extraordinarily nothingness of Mars, a new research study came front.
The Martian surface is presently cold and dry, however there's lots of proof suggesting that rivers, lakes and seas coated the terrestrial planet billions of years agone. Since there's life just about where there's liquid water on Earth, scientists have steered that life may need evolved on Mars once it absolutely was wet, eventually life might be there even currently.
“In all the environments we find here on Earth, there is some sort of microorganism in almost all of them,” said Rebecca Mickol, an astrobiologist at the Arkansas Center for Space and Planetary Sciences at the University of Arkansas in Fayetteville, and she is also the lead author of the study. “It’s hard to believe there aren’t other organisms out there on other planets or moons as well.”
The research was published in the journal Origins of Life and Evolution of Biospheres.
In this recent set of experiment which made them work for an year where microbes are grown in test tubes within liquids as creating an environment like liquids potentially flowing underground Martian aquifiers. Microbes were fed hydrogen gas, and also the liquids were lined with cotton swabs, that successively were lined with dirt simulating what may well be found on the Martian surface. The insides of every tube were then subjected to low pressures.
“Oxygen kills these methanogens (methane producing bacteria), and maintaining a low-pressure, oxygen-free environment was a difficult task,” Mickol said. “Moreover, water evaporates quickly at low pressure, which can limit how long the experiments can last and can also clog the vacuum system with water.”
Despite these issues, the researchers found that these methanogens all survived exposure of lengths variable from three to twenty one days at pressures all the way down to roughly six-thousandths of Earth’s surface pressure. These experiments show that for a few species, lower air mass might not extremely have any impact on the survival of the organism.
The scientists also measuring methane to envision whether or not methanogens are actively growing at lower preassure and manufacturing methane. Since methanogens grow mostly everywhere from guts of cattle to dead decaying organic matter. Previously most of the old and present microorganisms on Earth produced methane.
“The next step is to also include temperature,” Mickol said. “Mars is very, very cold, often getting down to -100ºC (-212ºF) at night, and sometimes, on the warmest day of the year, at noon, the temperature can rise above freezing. We’d run our experiments just above freezing, but the cold temperature would limit evaporation of the liquid media and it would create a more Mars-like environment.”
Source: Astro Biology
Tuesday, 24 January 2017
|Salty Martian waters (NASA/University of Arizona)|
Biofilms area unit everyplace on Earth, from plaque and chlorophyte to systems we have a tendency to use to scrub up oil spills. Here, biofilms will shield their inhabitants from radiation, antibiotics, temperature changes and different extreme environments that may otherwise kill them presently.
The behavior of biofilms on Earth is fairly well studied, however we have a tendency to are barely commencing to find out however they’d react to alien environments – that is crucial if we area unit to avoid contaminating different worlds.
Now, a research shows that storage away on a ballistic capsule may very well facilitate the microbes survive.
Although Mars is usually dry, we all know its ice caps contain water, and therefore the planet could even have seasonal streams to look at, however biofilms would possibly react to those Martian waters, Adam Stevens at the University of Edinburgh and his colleagues soused them in seven Mars-like brines with a variety of chemical compositions and strengths.
All of the biofilms did well within the weakest brines, lasting well past the 5-hour observation time. Because the brines got harsher, though, a divide began to appear: biofilms that were dried out before dunking did far better than regular biofilms with their water content intact.
Any biofilms that created it from Earth to Mars would in all probability be desiccated from the trip through the vacuum of house. It seems that this arduous ride may truly prepare them to thrive on Mars.
After a fleeting shock within the most intense brines, desiccated biofilms began to grow, presumptively protective themselves from their harsh atmosphere. This could be a consequence of communication throughout the biofilm: a cell on the skin fringe of the film, exposed to Mars’s viciously salty brines, may send an alert to the insulated cells deeper down. Those cells may either type a lot of gunk or reproduce a lot of quickly to create the barrier.
After five hours within the most intense brines, that were up to seventy times saltier than the weakest one, all the microbes within the desiccated biofilms were dead. The regular, hydrous biofilms did abundant worse: within the harsher brines, their cells died inside an hour. Some hydrous biofilms were finished in 0.5 an hour or less.
Microbes on Mars
On Mars, areas with water (even salty, briny water) are selected as “special regions” by the international Committee on space analysis. They’re the foremost possible spots to seek out Martian life, however conjointly the most effective places for Earth-based contaminants to thrive. As a result of any contamination might build it not possible to accurately study the regions, it is important to be very careful regarding causation any space vehicle or rovers to those regions.
Biofilms might facilitate Martian microorganisms survive, in order that they could be one thing to appear for in Mars’ briny continual slope lineage or within the salty seas of icy moons any go in our scheme. However the danger is that they may conjointly facilitate microbes from Earth thrive, reordering any previous life and polluting the science.
“This research gives us some information about what we could possibly look for if we do go and investigate these brines – which, on the flip side, we’re saying maybe we shouldn’t,” says Stevens.
“To me, this is a kind of a call to pick up the baton of this area that we really need to understand as we launch into an era of space travel,” says Jennifer Macalady at Penn State University in University Park.
Source: New Scientist
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