The Arkive
 
|| Year Gamma: London: Friday: July 13: 2018 ||
First Published: September 24: 2015
The Humanion

 

 

Microbial World

Spirulina: A microscope image of Arthrospira bacteria that are known as Spirulina.Spirulina has been harvested for food in South America and Africa for centuries. It turns carbon dioxide into oxygen, multiplies rapidly and can also be eaten as a delicious protein-rich astronaut meal. ESA astronaut Samantha Cristoforetti ate the first food containing spirulina in space. Image: ESA:NASA
 

 

 

 

 

 

 

 

 

 

 

 

 

Microbial World

The Humanion uses Machine Processed Programming:MPP for Machine or Artificial Intelligence and Programmed Algorithmic Machination:PAM for Machine Learning, refusing the very concepts that machines can have intelligence and that they are, therefore, capable to learn. Likewise, The Humanion does not use the terms, self-driven or self-driving or autonomous vehicles for machines are not and can not be deemed to be having 'self', that absolutely applies to humans and autonomy applies to humans as individuals and as groups, societies, peoples, nations etc and can not be applied to machines. Therefore, Auto-driven is the term we use for Self-driven or Self-driving or autonomous vehicles etc. This relates to profound, vital and fundamental issues and we must be careful as to how we use terminology, that, albeit, inadvertently, dehumanises humanity.

Eco-Friendly Water Treatment Works Best with Experienced Bacterial Flora

 

 

|| May 14: 2018: Lund University News || ά. Sustainable, biological filters, called, slow sand filters, have been used to filter drinking water since the 1800s. They don’t use any chemicals, create no waste and use very little energy. However, technologies, that meet modern requirements for control, monitoring and time-efficiency have become popular, while biological water treatment has been less favoured, since little has been understood about how it works. New research from Lund University in Sweden shows that not only are the older filters more efficient cleaners, they could be making a comeback soon with the help of new technology.

Older sand filters are more effective than new ones, a unique field study at a water treatment facility in southern Sweden shows. This is because the old filters have had the time to develop a specific ecosystem of hungry bacteria, that purify the water. The water is cleaned not only by mechanical filtering by the grains of sand, but by considerably smaller helpers as well. The fact that sand filters contain micro-organisms was, already, known. However, it was believed that sand filters helped to reduce the number of bacteria, which is not the case. “Sand filtration helps change the composition of the bacteria for the better. The bacteria deep in the sand filters can remove harmful bacteria, viruses, parasites and other unpleasant substances.

For example, the old sand beds, always,  filtered out unwanted E. coli bacteria, something, which the new sand filters were not, always, able to do.” says Ms Catherine Paul, Researcher in Water Resources Engineering and Applied Microbiology at Lund University. Not only do older filters appear to be more effective, the bacteria between different filters vary. The development of certain micro-organisms depends on the type of sand originally used as well as the 'food' they receive, that is, what kind of dirt is in the water. Consequently, the bacterial flora of the purified drinking water is a reflection of the bacteria in the specific sand filter it has passed through.

The study suggests that, much like a sourdough bread starter, new sand filters can benefit from the addition of sand 'starter', made of bacteria and sand from an older sand filter.

“Just as we increasingly talk about the importance of our intestinal flora for our well-being, we should, also, start talking about our 'sand flora'. The right flora keeps harmful substances out of our drinking water, so it is important to our health. It impacts the bacterial flora in our tap water and so far we know very little about how that can affect us.” says Ms Catherine Paul.

A technology for monitoring slow sand filters, flow cytometry, means we can now understand the micro-organisms in sand filters better. Like other drinking water technologies, we can now begin to fulfil certain criteria for slow sand filters, such as, short response times and alert systems better, the study shows.

This new understanding of microbiology could give the old method a boost and since it can, also, help newer technologies perform better, the sand filters can be a sustainable boost to drinking water treatment.

Key collaboration partners: Sydvatten and Sweden Water Research. The study was funded by the Swedish Research Council.

The Paper: Monitoring biofilm function in new and matured full-scale slow sand filters using flow cytometric histogram image comparison:CHIC: Science Direct
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It's a Virus-Life: You Know Not Where We Have Been and How We are Back: It's Full of Hazards and All Hailings and All Fallings That You Humans Can Not Understand

 

 

|| February 19: 2017: University of British Columbia News || ά.  An astonishing number of viruses are circulating around the Earth’s atmosphere and falling from it, according to new research from scientists in Canada, Spain and the U.S. But the question is how do they end up being up there in the first place? Well, the study will answer this question as it marks the first time scientists have quantified the viruses being swept up from the Earth’s surface into the free troposphere, that layer of atmosphere beyond Earth’s weather systems but below the stratosphere, where jet airplanes fly. The viruses can be carried thousands of kilometres there before being deposited back onto the Earth’s surface.

“Every day, more than 800 million viruses are deposited per square metre above the planetary boundary layer, that’s 25 viruses for each person in Canada.” said University of British Columbia Virologist Mr Curtis Suttle, one of the Senior Authors of a paper in the International Society for Microbial Ecology Journal. The findings, may, explain why genetically identical viruses are often found in very different environments around the globe. “Roughly 20 years ago we began finding genetically similar viruses occurring in very different environments around the globe.” says Mr Suttle. “This preponderance of long-residence viruses travelling the atmosphere likely explains why it’s quite conceivable to have a virus swept up into the atmosphere on one continent and deposited on another.”

Bacteria and viruses are swept up in the atmosphere in small particles from soil dust and sea spray. Mr Suttle and colleagues at the University of Granada and San Diego State University wanted to know how much of that material is carried up above the atmospheric boundary layer above 2,500 to 3,000 metres. At that altitude, particles are subject to long-range transport unlike particles lower in the atmosphere.

Using platform sites high in Spain’s Sierra Nevada Mountains, the researchers found billions of viruses and tens of millions of bacteria are being deposited per square metre per day. The deposition rates for viruses were nine to 461 times greater than the rates for bacteria.

“Bacteria and viruses are, typically, deposited back to Earth via rain events and Saharan dust intrusions. However, the rain was less efficient removing viruses from the atmosphere.” said Author and Microbial Ecologist Isabel Reche from the University of Granada.

The researchers, also, found the majority of the viruses carried signatures, indicating, they had been swept up into the air from sea spray. The viruses tend to hitch rides on smaller, lighter, organic particles suspended in air and gas, meaning they can stay aloft in the atmosphere longer.
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A Scientific Text on Bacterial Nepotism

 

|| October 29: 2017: University of Exeter News || ά. Natural selection quickly turns a melting pot of micro-organisms into a highly efficient community, new research shows. Scientists at the University of Exeter mixed together ten different methane-producing communities, populations of hundreds of microbial species, mainly, bacteria. Some of those communities were thriving, when grown on their own and some were performing poorly but when mixed together, samples containing all ten communities quickly started producing as much methane as the best of the ten.

Microbial communities, complex mixtures of species interacting with each other, are everywhere on and in our bodies, in soil and water, even, in clouds and volcanic hot-springs. The researchers focused on microbial communities producing methane because the amount of gas produced indicates how healthy the community is. This allowed a rare insight on the mechanisms, that govern the formation of such communities. The communities came from a variety of sources, including, biogas plants and cow dung.

The results, may have, implications beyond the biogas sector and if the same principle applies elsewhere it could be implemented in faecal transplants or soil probiotics, increasing crop yields. “The more communities we added to the mix, the higher the biogas yield.” said Dr Pawel Sierocinski, of the Environment and Sustainability Institute on the University of Exeter’s Penryn Campus in Cornwall.

“This shows that selection can operate on a whole community, rather than simply on single species or genes. We looked at the communities’ species composition after the experiment, by analysing their DNA and saw that the mixes were very similar to the healthiest single community not only in their methane production, but also, in terms of which microbes can be found in them.

Some organisms from weaker-performing communities, also, became part of the thriving mix. These bacterial immigrants made the mixes have a higher biodiversity, making such communities more efficient and stable. There are complex feeding chains within these communities, as some micro-organisms live off by-products of others.

Our research shows that microbes from well-performing communities are capable of pulling their fellow bacteria with them in something, we dubbed, ‘bacterial nepotism’. We were, also,  surprised how reproducible our findings were, our colleagues in France got the same results from totally independent tests, using a similar model.

For the public, there are many potential practical implications if future research confirms that the same rules stand for other types of communities. Learning such rules, that guide community behaviour allows us to harness them. For example, if our gut flora behaves in a similar way as methane-producing communities, we could use that to our benefit. We could mend the poor-performing communities by giving them a boost from the ones, that function well.”

The research, funded by the Biotechnology and Biological Sciences Research Council, was carried out by the universities of Exeter and Warwick, the Earlham Institute and the French National Institute for Agricultural Research. ω.

The Paper: Published in the journal Current Biology: A single community dominates structure and function of a mixture of multiple methanogenic communities

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Study Offers New Insights as to How Bacteria Form Flocks

 

|| September 19: 2017: University of Edinburgh News || ά. Scientists have shed light on how tiny organisms flock together, even, when they are present in very low numbers. The findings could provide fresh insights into how some infectious diseases are spread. It was previously known that certain swimming bacteria, including, E. coli and Salmonella, form flocks at high concentrations. In the new study, researchers found that it is only at extremely low concentrations, that bacteria do not ‘feel’ each other’s presence.

Flocking behaviour occurs among many living things, from bacteria to people. However, the process in micro-organisms is poorly understood and it remains unclear as to why they engage in such behaviour, researchers say. Such gatherings arise spontaneously in groups without a clear leader as a result of physical interactions among individuals, previous research suggests. Scientists at Edinburgh found that flocking behaviour in micro-organisms is more complex than was previously thought.

The research team created a computer model and analytic theory to study how single micro-organisms affect each other through backwashes, that each animal creates as it swims.

These flows enable bacteria to sense each other’s presence and interact at very low concentrations. The study, published in the journal Physical Review Letters, was supported by the Engineering and Physical Sciences Research Council, the Swedish Research Council and Intel. It was carried out in co-operation with scientists in France and Sweden.

''Up to now it was thought that the movements of swimming micro-organisms at low concentrations, are random and featureless. Surprisingly, our latest results show measurable signs, that the micro-organisms can interact, even, at very low densities, in a way, which, significantly, affects the physical properties of the environment.'' says Dr Alexander Morozov, School of Physics and Astronomy.
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How to Kill a Bacteria the Smart Way: Take the Electron Supply Away That Feeds It to Grow

Agneta Richter-Dahlfors. Image: Stefan Zimmerman

 

|| September 09: 2017: Karolinska Institutet News || ά. Conducting plastics found in smartphone screens can be used to trick the metabolism of pathogenic bacteria, report scientists at Karolinska Institutet in the scientific journal NPJ Biofilms and Microbiomes. By adding or removing electrons to and from the plastic surface, bacteria, may be, tricked into growing more or less. The method, may, find widespread use in preventing bacterial infections in hospitals or improve effectiveness in wastewater management.

When bacteria attach to a surface they grow quickly into a thick film, known as, a biofilm. These biofilms frequently occur in our surroundings but are, especially, dangerous in hospitals, where they can cause life threatening infections. Researchers have now aimed to address this problem by producing coatings for medical devices, made from a cheap conducting plastic, called, PEDOT, which is what makes smartphone screens respond to touch. By applying a small voltage, the PEDOT surface was either flooded with electrons or left almost empty, which in turn, affected the growth of Salmonella bacteria.

“When the bacteria land on a surface full of electrons, they cannot replicate.”, explains Principal Investigator Professor Agneta Richter-Dahlfors, at Karolinska Institutet’s Department of Neuroscience and Director of the Swedish Medical Nanoscience Centre. “They have nowhere to deposit their own electrons, which they need to do in order to respire.”

On the other hand, if the bacteria encountered an empty PEDOT surface, the opposite happened, as they grew to a thick biofilm. “With the electrons being continually sucked out of the surface, bacteria could continually deposit their own electrons, giving them the energy they needed to grow quickly.”, says Professor Richter-Dahlfors.

This left the research team in a position where, at the flick of a switch, they could either abolish bacterial growth or let it continue more effectively. This has many implications for both health and industry.

“To begin with, we can coat medical devices with this material to make them more resistant to colonisation by bacteria.” says Professor Richter-Dahlfors. “However, if we look to industries like wastewater management, that need a lot of beneficial biofilms to create clean water, we can produce surfaces, that will promote biofilm production.” she continues.

In the future the research team will work to integrate this technology into devices, that could, one day, be implanted into patients to keep them safe, when undergoing medical procedures or having devices implanted.

The study was financed by the Swedish Research Council, Vinnova, Carl Bennet AB, and the Swedish Medical Nanoscience Centre. ω.

The Paper: Redox-active conducting polymers modulate Salmonella biofilm formation by controlling availability of electron acceptor: Salvador Gomez-Carretero, Ben Libberton, Mikael Rhen, and Agneta Richter-Dahlfors: NPJ Biofilms and Microbiomes, online 4 September 04, 2017 doi:10.1038/s41522-017-0027-0

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The First Snapshots of Molecular Propeller of Archaea Pyrococcus Furiosus That Can Run at 100 Degrees Celsius

 

The 3D view of a Pyrococcus furiosus cell obtained by electron cryo-tomograpy next to the structural model depicting the position of every atom in the archaellum. Image: University of Exeter

 

|| September 05: 2017: University of Exeter News || ά. Scientists have made a crucial new discovery into how a group of ancient microbes, that can survive in some of the world’s harshest environments, propel themselves forward. An international team of experts, led by Dr Bertram Daum of the University of Exeter’s Living System Institute, have showed the structure of the unique whip-like appendage, found on archaea, which rotates like a propeller to enable these cells to swim.

The structure, called, the archaellum, is used for movement and to allow the microbes to adhere themselves to surfaces, helping them flourish in their current environments and to colonise new ones. The researchers studied a particular type of archaea, Pyrococcus furiosus, which thrive without needing oxygen and at a temperature of 100° C, the boiling point of water. Using advanced electron cryo-microscopy at the Max Planck Institute of Biophysics in Frankfurt, Germany, the research team have visualised this vital, yet, previously, poorly understood propelling motor in three-D and at so far unachieved resolution.

The researchers say that the new research will pave the way for a deeper, molecular understanding of the swimming motion of the archaea. The study is published in scientific journal eLife. Dr Daum, a Research Fellow from the University of Exeter’s College of Engineering, Mathematics and Physical Sciences, said, “The machinery, that drives these micro-organisms can appear strikingly simple but it is extremely difficult to study in depth. This new research has allowed us to create, for the first time, a detailed model of the structure, that propels the archaea, and as such, helps them to thrive and survive in places, that so much of life would perish.

More than that, this could have an incredible impact on synthetic biology and by understanding how archaea move, we are able to provide a new idea for future medical practices. Understanding the molecular propeller in detail could help scientists create motors for minute artificial capsules, small enough to explore inside the human body and help combat infectious diseases or cancer.”

As well as thriving in diverse and often harsh habitats across the world, such as, boiling hot springs, salt lakes or deep sea vents, archaea are, also, found in the human digestive system and have been implicated as playing a role in obesity.

We are really excited about our structure of the archaellum machinery because it has many downstream implications. Not only does it teach us about how life can exist at extreme conditions here on earth, and potentially, elsewhere in the universe, but it, also, provides us with a powerful and versatile tool to create revolutionary technology, that works at the level of molecules.” ω.

 

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What Have You Found in the Lake Jyväsjärvi: Something Stranded But Singly

 

|| July 23: 2017: University of Jyväskylä News || ά.  Viruses are the most numerous biological entities, where is life there are viruses. Still, only a small fraction of them have been structurally and biochemically characterised. A few years ago, during a laboratory course in University of Jyväskylä a new bacterial virus infecting a Flavobacterium host was isolated from a water sample taken from Lake Jyväsjärvi in Finland.

A more detailed analysis done in collaboration with scientists from Universities of Jyväskylä, Helsinki and Oxford showed the unique characteristics of this virus. The virus, named FLiP, was found to be the first described virus with an icosahedral capsid, internal lipid membrane and a single stranded DNA genome. Without the detailed near-atomic resolution structural analysis the exceptional characteristics of FLiP could have remained unnoticed.

Whereas the virus genome showed limited sequence. similarity to other known viruses, the structure of the viral major capsid protein was strikingly similar to that observed in double stranded DNA viruses of the PRD1–adenovirus lineage.

FLiP is the first ssDNA virus assigned in this lineage. These results suggest that the capsid protein structure could be used to complement the sequence data, when classifying viruses and in detecting their deep evolutionary relationships.

Furthermore, the finding of FLiP exemplifies the importance of detailed characterisation of novel viruses from diverse environments in detail to understand the diversity of the microbial world.

The study was publisher in Proceedings of National Academy of Sciences of the United States of America. ω.

Further information:  Academy Researcher Lotta-Riina Sundberg, tel. 358 40 805 3931, lotta-riina.sundberg at jyu.fi

The Paper: Laanto, E., Mäntynen, S., De Colibus, L., Marjakangas, J., Gillum, A., Stuart, D.I., Ravantti, J.J., Huiskonen, J.T., ja Sundberg, L.-R., 2017. Virus found from a boreal lake links ssDNA and dsDNA viruses. Proceedings of National Academy of Sciences of the United States of America. Doi: 10.1073/pnas.1703834114

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New Research in New Zealand Shows Potential for the First Gonorrhoea Vaccine

 

|| July 19: 2017: University of Auckland News || ά. New Zealand-led research has shown a link between the meningococcal group B vaccine:MeNZB, used here between 2004 and 2008 and a reduction in cases of gonorrhoea. The research, led by Dr Helen Petousis-Harris of the University’s Faculty of Medical and Health Sciences, has found exposure to the meningococcal group B vaccine during a New Zealand mass vaccination campaign was associated with a reduced likelihood of contracting gonorrhoea, compared with unvaccinated people.

It is significant because so far efforts to develop a vaccine against gonorrhoea have been unsuccessful despite more than a century of research. But population data suggests there is a decline in gonorrhoea immediately after the use of the outer membrane vesicle:OMV meningococcal group B vaccine in New Zealand, as well as, Cuba and Norway. The need for a gonorrhoea vaccine is now desperate as gonorrhoea has recently developed into a ‘superbug’ with some strains now resistant to all available treatments.

Due to a devastating epidemic of meningococcal disease in New Zealand, approximately, one  million individuals, 81 percent of the population under 20 years, received the MeNZB vaccine, during a mass immunisation programme in 2004-2006. The vaccine was made from the outer membrane:OMV of the meningococcal group B bacteria that was causing the epidemic.

The researchers used data for all people aged 15-30, who had been diagnosed with gonorrhoea or chlamydia or both, at 11 sexual health clinics across New Zealand, and who, were eligible to receive the MeNZB vaccine during the 2004-2006 vaccination programme. The study was a case-control study, that compared people with gonorrhoea to those with a similar disease, Chlamydia, to see if vaccination exposure differed between them.

A total of 14,730 cases and controls were included in the analysis, 1,241 cases of gonorrhoea, 12,487 cases of chlamydia, 1,002 cases of co-infection. Vaccinated individuals were significantly less likely to have gonorrhoea than controls. Taking into account all other factors, such as, ethnicity, deprivation, geographical area and gender, the researchers conclude that having previously received the MeNZB vaccine reduced the incidence of gonorrhoea by approximately 31 percent.

The study has just been published in prestigious journal the Lancet. Dr Petousis-Harris, says, “Our findings provide experimental evidence and a proof of principle that an OMV meningococcal group B vaccine could offer moderate cross-protection against gonorrhoea.

This is the first time a vaccine has shown any protection against gonorrhoea. At the moment, the mechanism behind this immunity is unknown, but our findings could inform future vaccine development for both the meningococcal and gonorrhoea vaccines. It, also, aises the question as to the effect currently available similar vaccines, may have.”

MeNZB was developed to control a meningococcal disease epidemic and is no longer available, but the OMV antigens thought to provoke the immune response to gonorrhoea have been included in the more recently developed 4CMenB vaccine, available in many countries. New Zealand, may, see the availability of this vaccine in the near future, too. It will be important to elucidate the mechanism behind this protection, and also, prove that other OMV vaccines have a similar effect.
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Bacteria: Micro-Flocking

 

 

|| July 17: 2017: Lund University News || ά. Many animal species display flocking behaviour, but the fact that micro-organisms do it, too, is not as well known. Researchers, at Lund University in Sweden, have now shown that algae and bacteria form flocks at very low concentrations of individuals, a finding that could increase our future understanding of how the organisms infect their host animals. Flocking behaviour in animals seemingly arises spontaneously in a group of independent individuals without a clear leader.

This behaviour occurs among all types of organisms, from bacteria to people. One hypothesis, therefore, is that there are fundamental principles for flock building, that are not dependent on single individuals. Researchers at Lund University, in co-operation with colleagues from the UK and France, have now found that flocking behaviour among micro-organisms is more advanced than we previously thought.

“Our research is a physical explanatory model of how micro-organisms move. From a biological perspective, it is useful to examine the evolutionary basis for flocking behaviour among bacteria, as the connections can increase our understanding of the course of infectious diseases.” says Joakim Stenhammar, chemistry researcher at Lund University.

When a person or animal swims, they create backwashes or wakes, that others can sense. The researchers have now created a theoretical model, that describes how single micro-organisms communicate with each other via the backwashes, that each organism creates.

The physical principle differs from ordinary backwashes, but these flows enable the bacteria to sense each other’s presence and affect each other at very low concentrations. In light of this, micro-organisms cannot be described as isolated individuals.

It was previously known that certain swimming bacteria, such as E. coli and Salmonella, form flocks at high concentrations. In the new study, Stenhammar and his colleagues have shown that it is only at extremely low concentrations, less than ten per cent of what was previously thought, that bacteria, can be, considered as individuals.

“In contrast to an individual bacterium, flocks can move in a synchronised way over long length scales and several times faster than a single bacterium.” says Joakim Stenhammar.

“Our research adds another piece of the puzzle to our understanding of how flocking behaviour works in biological systems and the model, can be, applied to a large number of swimming micro-organisms.” says Joakim Stenhammar.
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Publication: Role of Correlations in the Collective Behavior of Microswimmer Suspensions

Contact: Joakim Stenhammar: Associate Senior Lecturer: Department of Chemistry, Lund University: Tel. +46:0:707 22 61 12: Email: joakim.stenhammar at fkem1.lu.se

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The Verticillium-Specific Protein VdSCP7 Localises to the Plant Nucleus and Modulates Immunity to Fungal Infections

Figure: A. GFP-tagged VdSCP7 is secreted by V. dahliae and accumulates in the plant nucleus,
B. VdSCP7 gene knockout mutant, ∆vdscp7-1 showed enhanced virulence in
cotton host, C. Hypothesis of VdSCP7 activating plant immunity by translocation
from apoplastic space to the nucleus. Image: Professor Guo's group
 

 

|| April 18: 2017: Chinese Academy of Sciences News || ά. Verticillium dahliae:V. dahliae is a soil borne fungal pathogen, that infects a broad range of hosts. It is now becoming a major threat to many economically important crops, such as cotton and sunflower. Similar to most filamentous pathogens, V. dahliae secretes effector proteins to overcome plant basal defense for successful host colonisation.

Resistance plants can recognise effector by cognate R proteins to induce a second layer of immunity, known as effector-triggered immunity, ETI, against pathogen infection. However, very few R proteins were found to recognise V. dahliae effectors and trigger ETI. The research group, led by Professor Guo Huishan at State Key Lab of Plant Genomics, Institute of Microbiology, Chinese Academy of Sciences:IMCAS, has been working on V. dahliae pathogenesis and crop resistance against wilt diseases for over ten years.

Recently, they discovered a Verticillium-specific protein, namely VdSCP7, that functions as an effector and alters plant susceptibility to fungal and oomycete infection. The study was published in New Phytologist.

VdSCP7 was selected by proteomic analysis of the cultural filtrate from a cotton-isolated V. dahliae strain, V592. The protein contains N-terminal signal peptide and a nuclear localisation signal, that is secreted by V. dahliae and accumulates in the plant nucleus, Figure A. Expression of VdSCP7 in Nicotiana benthamiana induced immune responses such as ROS accumulation, callose deposition and HR.

Interestingly, VdSCP7-expressing N. benthamiana leaves showed resistance to the fungal pathogen Botrytis cinerea but enhanced susceptibility to the oomycete pathogen Phytophthoracapsici.

VdSCP7 gene knockout mutants showed enhanced virulence in cotton host, suggesting that there is a cognate R-gene in cotton that has triggered immunity against Verticillium infection, Figure B.

Researchers proposed a model that VdSCP7 could activate plant immunity by translocation from apoplastic space to the nucleus, Figure C. VdSCP7 is the first discovered nuclear effector in Verticillium species.
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Virologists Show How the Interplay Between CMV and HIV Infection and Seek to Develop Strategies to Eradicate the Latent Viruses

The study was led by led by Professor Chen Zhiwei, Director of the AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of
Medicine and Dr Allen Cheung Ka-loon, Post-doctoral Fellow of the AIDS Institute, Department of Microbiology,
Li Ka Shing Faculty of Medicine at HKU. Images: University of Hong Kong

 

|| February 22: 2017: University of Hong Kong News || ά. In recent years, breakthroughs in medical treatment of HIV:AIDS greatly extended the survival of infected patients, however, it remains an incurable disease. Previous studies have focused on the depletion of CD4 lymphocytes by human immunodeficiency virus type one:HIV-1 infection but little is known about the infection of CD34 stem cells. The AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong:HKU shows mechanistic interplay of two viruses, human cytomegalovirus:CMV and human immunodeficiency virus in co-infecting:CD34+ stem cells to establish latent reservoirs.

The findings, which show added difficulty in curing HIV-1, have been published recently in Blood Advances of American Society of Hematology. HIV-1 is the causing virus for AIDS. It destroys the white blood cells and impairs the body's immune system, making one susceptible to various opportunistic infections and cancers, which rarely affect healthy individuals. As of September 2016, there are 8,243 cumulative reported HIV cases, where more than 80% are men transmitted mainly through sexual contact. The incidence rate has risen from about 300 cases to more than 700 per year in the last ten years. CMV is a ubiquitous virus that has infected 60-100% of the world’s population.

Although, it remains asymptomatic in healthy individuals, it poses a fatal threat in congenital infection, organ transplant recipients and AIDS patients. CMV undergoes life-long latent infection in CD34 stem cells where HIV-1 can also infect them. Past studies have shown that progression to AIDS is faster in those HIV patients already infected with CMV, suggesting that CMV influences HIV-1. But there has been no research to study the interplay of these two viruses in CD34 stem cells.

The research team of the AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, HKU has initiated this study since 2013. They established a cell culture model using and expanding CD34 stem cells from blood and successfully revealed that HIV-1 and CMV can infect the same cell. These CD34 cells naturally reside in the bone marrow where they can hide from the immune system and antiviral drugs.

In addition, the research team found that pre-existing latent CMV assists HIV-1 infection of CD34 stem cells by 'opening a wider door' for the virus. CMV does this by increasing the co-receptors used by HIV-1 to gain entry into the cell as well as decreasing restriction factors. On the other hand, HIV-1 assists CMV by reverting the CD34 stem cell to a more primitive state to achieve a state of quiescent to ensure long-term survival.

Professor Chen Zhiwei, Director of the AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, HKU says, “The HKU research team is the first group to show in detail how HIV-1 and CMV co-operate in co-infecting CD34+ progenitor cells. The breakthrough findings highlight the importance to understand how both viruses interplay and what we need to consider to develop strategy to eradicate the latent viruses. With recent international focus to purge HIV-1 out of latency in patients, reservoirs of other viruses and niche cell types must be considered.”

About the research team: This research was conducted by the team led by Professor Chen Zhiwei, Director of the AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, HKU; and Dr Allen Cheung Ka-loon, Post-doctoral Fellow of the AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, HKU. ω.

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Research Teams Hone in on Zika Vaccines: But Challenges Remain

In Recife, Brazil, a 15-year-old mother holds her four-month-old baby born with microcephaly, caused by the Zika virus. Photo: UNICEF/Ueslei Marcelino


|| February 21: 2017: Beth Israel Deaconess Medical Centre News || ά. In less than one year, researchers have developed multiple vaccine platforms that provide robust protection against Zika virus challenge in animal models. Multiple phase one clinical trials have been initiated by government, industry and academic research institutions, including Beth Israel Deaconess Medical Centre. Research challenges remain, including the high bar for safety and efficacy needed to protect pregnant women and their fetuses from congenital Zika syndrome, which can cause devastating neurological defects in babies of infected mothers.

As public health officials warn that spring’s warmer temperatures may herald another increase of Zika virus infections in the Caribbean and North and South America, researchers around the world are racing to develop safe and effective measures to prevent the disease. In a review paper published today in the journal Immunity, a group of leading vaccine scientists, including Dan H. Barouch, MD, PhD, of Beth Israel Deaconess Medical Centre:BIDMC, outline advances in the hunt for a Zika vaccine and the challenges that still lie ahead.

“The pace of preclinical and early clinical development for Zika vaccines is unprecedented.” said Barouch, corresponding Author and Director of the Centre for Virology and Vaccine Research at BIDMC. “In less than a year, our group and others have demonstrated that multiple vaccine platforms can provide robust protection against Zika virus challenge in animal models. However, unique challenges will need to be addressed in the clinical development of a Zika vaccine. ”

The recent outbreak of the Zika virus in the Americas began in Brazil nearly two years ago. By February 2016, the World Health Organisation had declared the epidemic a global public health emergency, based largely on the virus’ newly-established link to microcephaly and other major birth defects in babies born to infected mothers. The virus has also been associated with the neurologic disorder Guillain-Barré syndrome in adults.

In a previously published paper, Barouch and colleagues, including Colonel Nelson L. Michael, MD, PhD, Director of the Military HIV Research Programme at the Walter Reed Army Institute of Research:WRAIR and Stephen Thomas, MD, Upstate Medical University, State University of New York, demonstrated that three different vaccine candidates provided robust protection against Zika virus in both mice and rhesus monkeys. Several human clinical trials began last fall at test sites including BIDMC, WRAIR and National Institute of Allergy and Infectious Diseases affiliated clinical trial sites.

“The rapid advancement of Zika vaccine candidates into clinical trials reflects the uniquely focused and effective collaboration among scientists in the field to address this important global problem.” said Barouch. Despite the accelerated pace of research, much remains unknown about the virus, raising unique challenges in developing a vaccine. Safety considerations are especially critical, given that the target population for a Zika vaccine would likely include men and women of childbearing age.

Zika is a member of the flavivirus family of viruses, which includes West Nile virus, yellow fever virus, and dengue viruses, for which successful vaccines have been developed. Studies suggest that Zika-induced antibody responses may also cross-react with other flaviviruses, particularly dengue virus. Whether or not this antibody cross-reactivity may have clinical consequences is another consideration for Zika vaccines and requires further study.

Co-authors include: Stephen J. Thomas, MD, Upstate Medical University, State University of New York, Syracuse; and Colonel Nelson L. Michael, MD, PhD, Director, Military HIV Research Program, at Walter Reed Army Institute of Research:WRAIR.

The review’s authors acknowledge support from the U.S. Military Research and Material Command and the U.S. Military HIV Research Program; the National Institutes of Health; and the Ragon Institute of MGH, MIT, and Harvard.

About Beth Israel Deaconess Medical Centre: Beth Israel Deaconess Medical Centre is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Centre, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Centre and Hebrew Rehabilitation Centre and is a research partner of Dana-Farber:Harvard Cancer Centre and the Jackson Laboratory. ω.

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Marine Bacteria Produce Molecule with Links to the Climate

Microscope images showing two species of algae which swim using tiny appendages known
as flagella. Image: Kirsty Y. Wan:Raymond E. Goldstein
 

|| February 19: 2017: University of East Anglia News || ά. Scientists from the University of East Anglia and Ocean University China have discovered that tiny marine bacteria can synthesise one of the Earth’s most abundant sulfur molecules, which affects atmospheric chemistry and potentially climate. This molecule, dimethylsulfoniopropionate:DMSP is an important nutrient for marine microorganisms and is the major precursor for the climate-cooling gas, dimethyl sulfide:DMS.

DMS, produced when microorganisms break down DMSP, is thought to have a role in regulating the climate by increasing cloud droplets that in turn reduce the amount of sunlight reaching the ocean’s surface. These same clouds are vital in the movement of large amounts of sulfur from oceans to land, making the production of DMSP and DMS a critical step in the global sulfur cycle. It was previously widely thought that only eukaryotes, ‘higher’ organisms with complex cells, such as seaweeds and phytoplankton, produced DMSP.

However, researchers have discovered that many marine bacteria also produce this sulfur compound and have identified the key gene in the process. “Our finding that DMSP is produced by many marine bacteria could mean that scientists have been significantly underestimating both the production of this molecule and the effects it is having in the environment.” said Dr Jonathan Todd from UEA’s School of Biological Sciences.

“Since these bacteria do not require sunlight for growth, the production of DMSP need not be confined to the surface ocean waters which receive the most light energy, as was thought to be the case.”

Dr Andrew Curson from UEA’s School of Biological Sciences said, “The identification of the key gene for DMSP synthesis in these bacteria will allow scientists to predict which bacteria are producing DMSP and assess their contribution to global production of this environmentally important molecule.”

Ana Bermejo Martinez, a UEA PhD student involved in this research, said, “Using DMSP-producing marine bacteria as model organisms will also help us to understand how and why the synthesis of this key molecule is regulated in different environments.”

Dr Zhang from OUC’s College of Marine Life Sciences said, “These bacteria, isolated during a research cruise in the East China Sea, have led to a ground-breaking discovery in the field. This work shows that marine bacteria are likely very important contributors to global DMSP and DMS production.”

This work was carried out as part of a collaboration between the University of East Anglia, and Ocean University China and work at UEA was funded by the UK Natural Environment Research Council. ω.

The paper ‘Dimethylsulfoniopropionate biosynthesis in marine bacteria and identification of the key gene in this process’ is published in the scientific journal Nature Microbiology.

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A Microscopic Fungus or Yeast Known as Pichia Found in Babies’ Guts Increases Risk of Asthma

Faculty of Medicine University of British Columbia: Image:UBC

|| February 17: 2017: University of British Columbia News || ά. University of British Columbia microbiologists have found a yeast in the gut of new babies in Ecuador that appears to be a strong predictor that they will develop asthma in childhood. The new research furthers our understanding of the role microscopic organisms play in our overall health. “Children with this type of yeast called Pichia were much more at risk of asthma.” said Brett Finlay, a Microbiologist at UBC. “This is the first time anyone has shown any kind of association between yeast and asthma.”

In previous research, Finlay and his colleagues identified four gut bacteria in Canadian children that, if present in the first 100 days of life, seem to prevent asthma. In a followup to this study, Finlay and his colleagues repeated the experiment using fecal samples and health information from 100 children in a rural village in Ecuador. Canada and Ecuador both have high rates of asthma with about 10 per cent of the population suffering from the disease. They found that while gut bacteria play a role in preventing asthma in Ecuador, it was the presence of a microscopic fungus or yeast known as Pichia that was more strongly linked to asthma.

Instead of helping to prevent asthma, however, the presence of Pichia in those early days puts children at risk. Finlay also suggests that there could be a link between the risk of asthma and the cleanliness of the environment for Ecuadorian children. As part of the study, the researchers noted whether children had access to clean water.

“Those that had access to good, clean water had much higher asthma rates and we think it is because they were deprived of the beneficial microbes.” said Finlay. “That was a surprise because we tend to think that clean is good but we realise that we actually need some dirt in the world to help protect you.”

Now Finlay’s colleagues will re-examine the Canadian samples and look for the presence of yeast in the gut of infants. This technology was not available to the researchers when they conducted their initial study.

This research was a collaboration with Marie-Claire Arrieta, a former UBC Postdoctoral Fellow and now an Assistant Professor at the University of Calgary, and Philip Cooper, a Professor at the Liverpool School of Tropical Medicine. This research was presented today at the 2017 annual meeting for Association for the Advancement of Science. ω.

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Ebola Super-Spreaders Were a Driving Force of West Africa Epidemic



 

|| February 15: 2017: London School of Hygiene and Tropical Medicine News || ά. The majority of cases during the 2014-15 West African Ebola outbreak were down to a small percentage of patients or ‘super-spreaders’, according to new research published in Proceedings of the National Academy of Sciences. Co-authored by the London School of Hygiene and Tropical Medicine and led by Princeton University, the research found that 61% of cases were caused by 03% of infected people. The authors noted that their findings were a conservative estimate, since they focussed on people who had been buried safely, whereas it is known that unsafe funerals can be a major source of onwards transmission of Ebola.

The study highlights the significance of super-spreading and the need to better identify the social or biological factors behind it. It might then be possible to improve measures designed to control the spread of infectious disease during epidemics. Focusing on cases in and around Freetown, Sierra Leone, the researchers concluded that children under 15 years old and adults over 45 were more likely to infect a large number of others. Although the authors did not have access to information, which would have allowed them to investigate further, it’s possible a combination of factors could be behind this effect.

Biologically, those who experienced more severe disease may have shed more infectious material and therefore, been more infectious than others. Socially, the groups found to be causing more onwards transmission may have been cared for or visited by, more people than others when they were ill and at their most infectious.

Dr Sebastian Funk, Director of the Centre for the Mathematical Modelling of Infectious Diseases at the London School of Hygiene and Tropical Medicine and study Co-author, said, “Our best chance of preventing widespread outbreaks is to clamp down on them as soon as they begin.

Studies such as this one provide vital clues on how best to do that, including which groups of people are the most infectious but we also need to know what occasions or events are catalysts for transmission. The scale of the recent Ebola epidemic in West Africa was unprecedented and early control measures failed. Targeting measures at the individuals and social contexts most likely to cause further cases may have helped end it more quickly.”

The concept of super-spreaders is not new and there is a greater appreciation that not all individuals play an equal role in spreading an infectious disease. Super-spreaders have also been implicated in other outbreaks, including severe acute respiratory syndrome:SARS in 2003; and the more recent Middle East respiratory syndrome:MERS in 2012.

This study showed how super-spreading changed over time, as the epidemic progressed and as control measures were implemented. ω.

Publication: Max S. Y. Lau, Benjamin Douglas Dalziel, Sebastian Funk, Amanda McClelland, Amanda Tiffany, Steven Riley, C. Jessica E. Metcalf, Bryan T. Grenfell. Spatial and temporal dynamics of superspreading events in the 2014–2015 West Africa Ebola epidemic. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1614595114

The Humanion Calls on the Word Universities to Unite  Into a Universal United Nations of Universities: For Acting as the Universal Human Bank of Learning, Knowledge, Research, Innovations and Investments: To Begin with to Advance Non-Profit Drug Development


|| February 14: 2017: The Institute of Cancer Research London: England: United Kingdom News || ά. As we report this news from The Institute of Cancer Research London, England, United Kingdom, The Humanion calls on the word universities to unite into a Universal United Nations of Universities or for short, UUNU: One for Many Many as One for the Light: for acting as the Universal Human Bank of Learning, Knowledge, Research, Innovations and Investments. To begin with to advance non-profit drug development. This is not envisioned as anything that exists at the moment. This, if constituted properly and with proper commitment, can become the 'richest' universal body because it will receive, in addition to an opening fund and through all existing means and modes of fund generation, philanthropic direct donations from across the globe, which it will raise every day through all possible existing channels, and added, all the world universities' individual assets together, which is going to be 'colossal' if added together, can work as the largest guarantee to raise as much funding from 'financial bodies' for anything it would like to invest in. And it will have an opening investment from all the participating universities of the world and every single university must must must be inspired to join in. This can and will be the 'Revolution' of this Century if we can inspire the visionaries of the world to put their thinking caps on.

And here is the news. Universities should work with new forms of commercial partner to take their own cancer drugs to market and drive down the ‘spiralling’ cost of new medicines, leading experts propose. A high-profile commentary warns that the price of cancer drugs is now rising so fast it threatens the whole financial viability of cancer treatment, particularly as the increased use of drug combinations multiplies costs. The authors propose that expert drug discovery teams in academia could develop cancer drugs more cheaply by working with new forms of private enterprise as an alternative to the traditional pharmaceutical industry model. The commentary, How much longer will we put up with $100,000 cancer drugs?, puts forward a series of radical solutions to disrupt the drug discovery and development system and provide real competition for the conventional pharmaceutical industry approach. Readmore

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Salmonella Typhimurium: Well, We Act for Our Own Good: Not Yours: But You May Learn From Us So That You Can Help Yourselves

A Salk Institute study shows how Salmonella blocks the appetite loss response in hosts
to both make the host healthier and promote the bacteria’s survival and transmission.


|| February 06: 2017: The Salk Institute News: La Jolla: San Diego: California: US || ά. The last time you had a stomach bug, you probably didn’t feel much like eating. This loss of appetite is part of your body’s normal response to an illness but is not well understood. Sometimes eating less during illness promotes a faster recovery, but other times, such as when cancer patients experience wasting, the loss of appetite can be deadly. Now, research from the Salk Institute shows how bacteria block the appetite loss response in their host to both make the host healthier and also promote the bacteria’s transmission to other hosts.

This surprising discovery, published in the journal Cell on January 26, 2017, reveals a link between appetite and infection and could have implications in treating infectious diseases, infection transmission and appetite loss associated with illness, aging, inflammation or medical interventions, like chemotherapy. “It’s long been known that infections cause loss of appetite but the function of that, if any, is only beginning to be understood.” says Janelle Ayres, Assistant Professor at Salk Institute’s Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis. Mice orally infected with the bacteria Salmonella Typhimurium typically experience appetite loss and eventually become much sicker as the bacteria become more virulent, spreading from the intestines to other tissues in the body.

Ayres’ team tested different conditions in the infected mice and found that sick mice that consumed extra calories despite their appetite loss actually survived longer. It turns out this survival wasn’t due to a more active immune response by well-fed animals, as measured by levels of the bacteria in the host. Instead, it was because the Salmonella weren’t spreading outside of the intestines and throughout the body when the mice ate more, which enabled the animals to stay healthy despite infection. Even more surprising, the Salmonella were acting on the intestine to try to suppress the appetite loss in the host.

Janelle Ayres and Sheila Rao: Salk Institute


The finding was initially puzzling: why would the bacteria become less virulent and not spread to other areas in the body when nutrients were more plentiful? And why would Salmonella actively promote this condition? It turns out the bacteria were making a trade off between virulence, which is the ability of a microbe to cause disease within one host, and transmission, which is its ability to spread and establish infections between multiple hosts.

“What we found was that appetite loss makes the Salmonella more virulent, perhaps because it needs to go beyond the intestines to find nutrients for itself. This increased virulence kills its host too fast, which compromises the bacteria’s ability to spread to new hosts.” explains Sheila Rao, a Salk research associate and the first author on the study. “The trade off between transmission and virulence has not been appreciated before, it was previously thought that virulence and transmission were coupled.”

When the host ate more and survived longer during infection, the Salmonella benefitted: bacteria in those mice were able to spread via faeces to other animals and increase its transmission between hosts, as compared to bacteria in mice who didn’t eat and died sooner due to heightened bacterial virulence. The researchers discovered that, to halt the appetite-loss response and boost transmission between hosts, Salmonella produces a molecule called SlrP, which blocks activation of an immune protein, cytokine, in the intestines. This cytokine typically communicates with the brain’s appetite centre, called the hypothalamus, to prompt the host to lose its appetite during infection. The team found that mice infected with Salmonella that couldn’t make SlrP ate less food while infected, lost more weight and died faster than control mice.

Though the same gut-brain pathway tied to appetite loss exists in the human as in mice, Ayres cautions that infection responses are dependent on many factors and that whether eating or fasting, during illness can improve one’s health will depend in large part on what the causative agent of the infection is. Her team is planning to search the human microbiome, the collection of bacteria that live in people’s bodies, to find other microbes that might have a similar effect on this pathway and explore those for new therapies tied to appetite loss and treating disease. The lab also wants to investigate whether drugs could be used to turn up or down the sickness-induced appetite-loss pathway that SlrP targets.

“Now that we’d identified this mechanism that regulates appetite, we want to turn it on the flip side and see if we can decrease appetite via this mechanism to help in cases of metabolic disease.” says Ayres.

The discovery also points to the further ground-breaking possibility of treating infectious diseases with approaches other than antibiotics, such as nutritional intervention. “Finding alternatives to antibiotics is incredibly important as these drugs have already encouraged the evolution of deadly antibiotic-resistant strains.” says Ayres. In the United States alone, two million people annually become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections, according to the U.S. Centres for Disease Control.

Other researchers on the study were Alexandria M. Palaferri Schieber, Carolyn P. O’Connor, Mathias Leblanc and Daniela Michel of the Salk Institute.

The work and the researchers involved were supported by grants from the National Institutes of Health, the Nomis Foundation, the Searle Scholar Foundation and the Ray Thomas Edward Foundation. ω.

Images: Salk Institute

The Humanion Invites Those of You in Large National and Multinational Organisations with Large Charitable Budgets and Those Philanthropic Minds Seeking to Support Causes for Great Benefits to Humanity to Support The Salk Institute's Salk and Women Programme to Create Opportunities for Diverse Range of Women to Enter the Fields of Science: This is Not Just a Donation But the Most Visionary Kind of Investment That Can Be Made: Here are Some of the Salk Women and to Show Our Support We Have Added The Humanion's Equality-Liberty-Soul That One Day the Universe Painted in the Sky

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New Approach to Deliver Polio Vaccines

The image above is an electron micrograph of live poliovirus particles, left and empty particles, potential VLP vaccine, right.
The VLPs contain no infectious viral RNA and so the stain used fills the empty space making them appear black.
Image: University of Leeds

 

|| February 05: 2017: University of Leeds News || ά. Scientists have identified new ways to provide vaccines against polio, which do not require the growth of live virus for their manufacture. Despite the success of vaccines produced from 'virus-like particles':VLPs for hepatitis B and human papilloma viruses, poliovirus VLPs have proved to be too unstable to make practical vaccines. Now, a research team at the University of Leeds has found a new way to modify these VLPs, also known as 'empty capsids', by identifying mutations which make their structures sufficiently stable to act as vaccines.

The empty capsids change shape when warmed and become unusable as vaccines but the mutations identified in this research prevent these damaging changes. Polio is on the verge of being eradicated world-wide but even when it has been officially declared as extinct as a disease, governments will need to continue to vaccinate to ensure it does not recur. Using current technology, the production of vaccine requires the growth of enormous quantities of live virus, which is then chemically killed, thus presenting a dangerous security risk of virus escaping into the environment.

These stabilised VLPs are suitable as replacements for the killed poliovirus vaccines and can be produced in ways that do not require the growth of live virus. The Leeds team and collaborators say that this form of vaccine, using the newly developed stabilised VLPs, would be best used after the virus has been eradicated.

David Rowlands, Professor of Molecular Virology and Co-Leader of the study at the University, said, “Continuing to vaccinate after polio has been eradicated is essential to ensure against the disease recurring but there are significant biosafety concerns about current production methods. Our new method of creating the vaccine has been proven to work in lab conditions and on top of that we’ve proved it’s actually more stable than existing vaccines.

The improved stability of these modified VLPs means that they can be produced using bioengineering techniques without involving the growth of live virus.” This study was a lab experiment, which showed stabilised VLPs to be effective in a controlled environment. Further research using animals, rats and mice, is planned, as part of the essential process of making sure the new VLPs are safe and effective for use in humans.

Professor Nicola Stonehouse, co-leader of the study, from the University of Leeds, said: “The international drive to eradicate polio using existing vaccines continues, but methods need to be found to maintain vaccination safely as insurance after it appears to have been eradicated. This is when our approach will come into its own.

Further research is needed to refine them more but we are confident they will work for all three forms of polio. After that we need to find a way to manufacture them cost effectively on a large scale.” The research has been funded through a $01.5 million World Health Organisation grant to a consortium led by Leeds and including the National Institute for Biological Standards and Control:NIBSC, John Innes Centre:JIC in Norwich, the University of Oxford, University of Reading, and the Pirbright Institute.

Further information: The research paper Increasing Type One Poliovirus Capsid Stability by Thermal Selection, by Oluwapelumi O. Adeyemi, Clare Nicol, Nicola J. Stonehouse, and David J. Rowlands was published on January 31  in the February 2017 edition of the Journal of Virology.

The results come in the same month as other members of the Leeds-led consortium:NIBSC also published a related paper in the PloS Pathogens journal describing a slightly different approach to the development of stable polio VLP vaccines. ω.

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Certain Anti-Influenza Compounds Also Inhibit Zika Virus Infection



This is a female Aedes aegypti mosquito, carrier of Zika: Image: UN Photo

|| January 18: 2017: University of Helsinki News: Mari Kaunisto Writing || ά. Researchers at the University of Helsinki have shown that three anti-influenza compounds effectively inhibit Zika virus infection in human cells. The results provide the foundation for development of the broad-spectrum cell-directed antivirals or their combinations for treatment of Zika and other emerging viral diseases. Globalisation, environmental changes, population growth and urbanisation make emerging virus diseases a major threat to public health. An example of such epidemics is the Zika outbreak which is ongoing in the Americas after emerging in the Pacific region.

Zika infection associated with congenital brain abnormalities is one of the eleven virus diseases that, according to World Health Organisation, needs urgent research and drug development attention. At the moment, there are no approved therapies for Zika infection. Several host cell targets are needed for replication of influenza and many other viruses. In contrast to viral proteins, the host targets are less prone to mutations and thus drugs targeting them could be more effective against viruses, which mutate easily.

A team led by Dr. Denis Kainov from the Institute for Molecular Medicine Finland:FIMM and Professor Olli Vapalahti from the Departments of Virology and Veterinary Biosciences, from the University of Helsinki, decided to adopt this approach to test cell-directed compounds for treatment of Zika. In their recent study, published online in the Antiviral Research journal, the researchers showed that antivirals which block influenza virus by targeting host cell factors are also able to inhibit Zika virus infection.

The multinational research group utilised a model system where human retinal pigment epithelial cells were infected with Zika virus strain they isolated earlier from foetal brain. They were able to show that treatment of the cells with three drugs, called obatoclax, saliphenylhalamide and gemcitabine, prevented synthesis of viral building blocks and production of new viruses at concentrations that are not toxic to cells.

''Our results show that these antiviral drugs and their combinations are potent inhibitors of Zika virus-host cell interaction. Furthermore, the results broaden the spectrum of antiviral activity of these compounds and shed new light on their mechanisms of action.'' said Dr. Kainov.

''Importantly, the findings of the study demonstrate that re-purposing commercially available, approved drugs or drug candidates may accelerate development of treatment against Zika and can provide a toolbox to target also other emerging viral diseases.'' Prof. Vapalahti added.

Kuivanen S, Bespalov MM, Nandania J, Ianevski A, Velagapudi V, De Brabander, JK, Kainov DE, Vapalahti O. Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism. Antiviral Res. 2017; 139: 117-128. doi:10.1016/j.antiviral.2016.12.022.

For further cotanct: Professor Olli Vapalahti: Departments of Virology and Veterinary Biosciences: olli.vapalahti at helsinki.fi: Tel. +358294126380
Group Leader Denis Kainov: Institute for Molecular Medicine Finland:FIMM: denis.kainov at helsinki.fi. ω.

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Malaria Infection Depends on Number of Parasites, Not Number of Mosquito Bites



This is a female Aedes aegypti mosquito: Not Aedes albopicturs: Image: UN Photo

|| January 14: 2017: Imperial College News: Hayley Dunning Writing || ά.  For the first time, researchers have shown that the number of parasites each mosquito carries influences the chance of successful malaria infection. The finding has implications for vaccine development and studies into how the disease spreads in the field. The findings, from scientists at Imperial College London, may also explain why the only registered malaria vaccine, RTS,S, has had only partial efficacy in recent trials. Malaria is spread when mosquitoes bite humans and release microscopic parasites, which live in the salivary glands of the mosquitoes, into the person’s bloodstream.

The parasites then travel to the liver, where they mature and multiply for 08-30 days before spreading throughout the bloodstream and causing the symptoms of malaria. Not every infectious mosquito bite will result in malaria. To determine the intensity of malaria transmission, researchers and international organisations like the World Health Organisation currently rely on a measure called the entomological inoculation rate:EIR: the average number of potentially infectious mosquito bites per person per year. However, this does not take into account how infectious each of those bites may be, each bite is considered equally infectious.

Previous studies using needle-injected parasites have suggested this may not be the case, but there have been no comprehensive studies using biting mosquitoes, which more accurately reflect real-world scenarios. Now, in a study funded by the PATH Malaria Vaccine Initiative and the Medical Research Council, published in the journal PLoS Pathogens, researchers have determined that the number of parasites each individual mosquito carries influences whether a person will develop malaria. Some mosquitoes can be ‘hyperinfected’, making them particularly likely to pass on the disease.

In studies in mice, the researchers determined that the more parasites present in a mosquito’s salivary glands, the more likely it was to be infectious, and also the faster any infection would develop. Study co-author Dr Andrew Blagborough, from the Department of Life Sciences at Imperial, said, “These findings could have significant implications for public health. We have shown that the concept of relying on the number of bites alone to predict malarial burden is flawed, and has probably hampered the successful use of control measures and the development of effective vaccines.

It is surprising that the relationship between parasite density and infectiousness has not been properly investigated before, but the studies are quite complex to carry out.” The team set up repeated cycles of infection, so that groups of infected mosquitoes containing variable numbers of parasites repeatedly bit sedated mice, transmitting malaria to them under a range of transmission settings. This allowed them to track how many individual parasites different mosquitoes harboured, how many mice were infected as a result of exposure to them, and how long it took the mice to develop malaria.

By conducting further studies with mice and human volunteers, the team were also able to explain why the malaria vaccine RTS,S is effective only around 50 percent of the time, and why any protection rapidly drops off after three years. The vaccine was less effective when mice or humans were bitten by mosquitoes carrying a greater number of parasites. The researchers think this is because the vaccine can only kill a certain proportion of the parasites, and is overwhelmed when the parasite population is too large.

All malaria-affected regions will have a mix of mosquitoes carrying different parasite amounts. Dr Blagborough said, “The majority of mosquitoes in the wild are either uninfected or infected at quite low levels, but some individual mosquitoes are regularly very highly infected. As the levels of malaria drop in an area due to the successful use of interventions, the number of these hyperinfected mosquitoes is expected to drop, but they’re not totally prevented unless the intervention is very powerful.”

Study co-author Dr Thomas Churcher, from the MRC Centre for Outbreak Analysis and Modelling at Imperial, said, “Vaccine development has come a long way, and this new insight should help future vaccine studies to be tested more rigorously. However, in the end, it is unlikely that one magic bullet will eradicate malaria, and we should continue to seek and apply combinations of strategies for reducing the burden of this disease.”

Dr Morvern Roberts, Programme Manager for global infections at the Medical Research Council who funded the research, said, “Researchers have long wondered whether the more malaria parasites in a mosquito’s mouthparts, the more likely they are to infect a host with the disease. No one has been able to demonstrate this until now but the authors of this paper have shown that this is the case in both mouse models and in humans. As they suggest, this knowledge is extremely important to take into account when trying to develop vaccines for malaria and other vector-borne diseases.”

Publication: Probability of Transmission of Malaria from Mosquito to Human is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts by Thomas S. Churcher et al, is published in PLoS Pathogens.

Hayley Dunning: Research Media Officer: Central Faculty, Communications and Public Affairs Imperial College

: This Article text is published under an Attribution-NonCommercial-ShareAlike Creative Commons license. The Humanion has no connection with the Author or the Licensor: ω.

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Link Between Stomach Acid Medications and Gastrointestinal Infections

Arthrospira Bacteria Or Spirulina


|| January 11: 2017: London School of Hygiene and Tropical Medicine News || ά. A type of medication widely used to treat indigestion is associated with an increased risk of bacterial gastroenteritis, as according to new research published in the British Journal of Clinical Pharmacology. The research, led by University College London found that people taking acid suppression medications, such as protein pump inhibitors:PPIs, were nearly four times at risk of suffering infection from Campylobacter jejuni, one of the most common causes of food poisoning.

The study found a higher associated risk of severe intestinal infection from other pathogens including C. difficile and E. coli. PPIs are drugs that act on the cells that line the stomach to reduce the production of acid. These are different from common indigestion and heartburn treatments, which neutralise rather than reduce excess stomach acid. Are these findings a surprise and what are the reasons behind them?

Brendan Wren, Professor of Microbial Pathogenesis at the London School of Hygiene and Tropical Medicine, said, “The study clearly shows that patients on proton pump inhibitors:PPIs are more at risk of developing diarrheal disease.

A likely explanation for this is that PPIs reduce acid in the stomach which is a mechanism to reduce ingested bacteria reaching our intestines. It is therefore not surprising that these drugs alter patient’s susceptibility to food poisoning organisms, such as Campylobacter jejuni, and alter a balanced microflora in the intestines that is required to prevent the colonisation of Clostridium difficile. An outcome of the study is that patients on PPIs should practise healthy hygiene.” ω.

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Gut Micro-organisms Affect the Physiology

Well, this should for now


|| January 08: 2017: University of Exeter News || ά. Researchers have found evidence that could shed new light on the complex community of trillions of micro-organisms living in all our guts, and how they interact with our bodies. Scientists at the University of Exeter Medical School and University of Zaragoza in Spain studied a protein known as TLR2, a critical detector of the microbiota found in the intestine. They found that it regulates levels of serotonin, a neurotransmitter which carries messages to the brain, and is also found in the gut, where it regulates our bowel routines.

The research, carried out in cell cultures and verified in mice, provides strong evidence that microbiota can interfere with human physiology by modulating the serotonin transporter activity. Serotonin transporter is a target for numerous diseases and it seems that microbiota living in our guts is able to interfere with this transporter, controlling our serotonin levels. The finding, published in PLOS ONE, comes as scientists across the world are working to understand the complicated interactions between the 'invisible world' of the microbiota in our bodies and the impact they have on our health and even our moods. Recently, scientists in California found evidence that the bacteria in the gut play a role in causing Parkinson’s Disease.

It may also help explain how the microbiota in our guts affect our physiology. Inflammatory bowel disease is thought to be triggered when TLR2 is not functioning properly, but so far, the mechanisms behind this have not been fully understood. This study aimed to further this understanding, and was supported the Foundation for the Study of Inflammatory Bowel Diseases in Aragón:ARAINF, in Spain.

Dr Eva Latorre, a postdoctoral researcher at the University of Exeter Medical School, said that the new finding helped to further understanding in a fast-growing research area. She said, “This paper has concluded that the protein TLR2 alters the availability of serotonin, which is important in a range of conditions from depression to inflammatory bowel disease. It is early days in this research though. We need to understand much more about the relationship between the microbiota in our guts and how they interact, before we can hope to harness effective new treatments.”

The research team examined human cells in a model of the intestine in the laboratory, looking at how they express proteins and RNA – activities which regulate how they behave. They found that TLR2 controls serotonin transporter, obtaining the same result in studies on mice.

Principal investigator of this study, Professor José E Mesonero, at the University of Zaragoza, said: “This paper opens our minds about the complex universe of this forgotten organ: the microbiome. We have concluded that TLR2 not only can detect microbiota, but also modulate serotonin transport, one of the crucial mechanism in neurological and inflammatory diseases. Much has to be yet studied, but this work can improve our understanding about the connection between gut and brain thought microbiota.”

The paper, called ‘Intestinal serotonin transporter inhibition by Toll-like receptor 2 activation. A feedback modulation’, is published in PLOS ONE, by Eva Latorre, Elena Layunta, Laura Grasa, Marta Castro, Julián Pardo, Fernando Gomollón, Ana I. Alcalde and José E. Mesonero. ω.

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Final Trial Results Confirm Ebola Vaccine Provides High Protection Against the Disease

Image: MSF:Sophia Apostolia


|| December 23: 2016 || ά. An experimental Ebola vaccine was highly protective against the deadly virus in a major trial in Guinea, according to results published yesterday in The Lancet. The vaccine is the first to prevent infection from one of the most lethal known pathogens and the findings add weight to early trial results published last year. The vaccine, called rVSV-ZEBOV, was studied in a trial involving 11,841 people in Guinea during 2015. Among the 5,837 people who received the vaccine, no Ebola cases were recorded 10 days or more after vaccination. In comparison, there were 23 cases 10 days or more after vaccination among those who did not receive the vaccine.

The trial was led by the World Health Organisation, together with Guinea’s Ministry of Health, Medecins Sans Frontieres and the Norwegian Institute of Public Health, in collaboration with other international partners. “While these compelling results come too late for those who lost their lives during West Africa’s Ebola epidemic, they show that when the next Ebola outbreak hits, we will not be defenceless.” said Dr Marie-Paule Kieny, WHO’s Assistant Director-General for Health Systems and Innovation, and the study’s lead author. The vaccine’s manufacturer, Merck, Sharpe and Dohme, this year received Breakthrough Therapy Designation from the United States Food and Drug Administration and PRIME status from the European Medicines Agency, enabling faster regulatory review of the vaccine once it is submitted.

Since Ebola virus was first identified in 1976, sporadic outbreaks have been reported in Africa. But the 2013-2016 West African Ebola outbreak, which resulted in more than 11,300 deaths, highlighted the need for a vaccine. The trial took place in the coastal region of Basse-Guinée, the area of Guinea still experiencing new Ebola cases when the trial started in 2015. The trial used an innovative design, a so-called 'ring vaccination' approach, the same method used to eradicate small pox.

When a new Ebola case was diagnosed, the research team traced all people who may have been in contact with that case within the previous three weeks, such as people who lived in the same household, were visited by the patient, or were in close contact with the patient, their clothes or linen, as well as certain “contacts of contacts'. A total of 117 clusters or 'rings' were identified, each made up of an average of 80 people.

Initially, rings were randomised to receive the vaccine either immediately or after a three-week delay, and only adults over 18 years were offered the vaccine. After interim results were published showing the vaccine’s efficacy, all rings were offered the vaccine immediately and the trial was also opened to children older than six years.

In addition to showing high efficacy among those vaccinated, the trial also shows that unvaccinated people in the rings were indirectly protected from Ebola virus through the ring vaccination approach, so called 'herd immunity'. However, the authors note that the trial was not designed to measure this effect, so more research will be needed.

“Ebola left a devastating legacy in our country. We are proud that we have been able to contribute to developing a vaccine that will prevent other nations from enduring what we endured.” said Dr KeÏta Sakoba, Co-ordinator of the Ebola Response and Director of the National Agency for Health Security in Guinea.

To assess safety, people who received the vaccine were observed for 30 minutes after vaccination, and at repeated home visits up to 12 weeks later. Approximately half reported mild symptoms soon after vaccination, including headache, fatigue and muscle pain but recovered within days without long-term effects. Two serious adverse events were judged to be related to vaccination, a febrile reaction and one anaphylaxis, and one was judged to be possibly related, influenza-like illness. All three recovered without any long term effects.

It was not possible to collect biological samples from people who received the vaccine in order to analyse their immune response. Other studies are looking at the immune response to the vaccine including one conducted in parallel to the ring trial among frontline Ebola workers in Guinea. “This both historical and innovative trial was made possible thanks to exemplary international collaboration and coordination, the contribution of many experts worldwide, and strong local involvement.” said Dr John-Arne Røttingen, specialist director at the Norwegian Institute of Public Health, and the chairman of the study steering group.

In January, GAVI, the Vaccine Alliance provided US$05 million to Merck towards the future procurement of the vaccine once it is approved, prequalified and recommended by WHO. As part of this agreement, Merck committed to ensure that 300,000 doses of the vaccine are available for emergency use in the interim, and to submit the vaccine for licensure by the end of 2017. Merck has also submitted the vaccine to WHO’s Emergency Use and Assessment Listing procedure, a mechanism through which experimental vaccines, medicines and diagnostics can be made available for use prior to formal licensure.

Additional studies are ongoing to provide more data on the safety of the vaccine in children and other vulnerable populations such as people with HIV. In case of Ebola flare-ups prior to approval, access to the vaccine is being made available through a procedure called “compassionate use” that enables use of the vaccine after informed consent. Merck and WHO’s partners are working to compile data to support license applications.

The rapid development of rVSV-ZEBOV contributed to the development of WHO’s R&D Blueprint, a global strategy to fast-track the development of effective tests, vaccines and medicines during epidemics.

The rVSV-ZEBOV trial is funded by WHO, with support from the Wellcome Trust; the United Kingdom Department for International Development; the Norwegian Ministry of Foreign Affairs; the Norwegian Institute of Public Health through the Research Council of Norway; the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, the International Development Research Centre and the Department of Foreign Affairs, Trade and Development; and Médecins Sans Frontières.

The trial team includes experts from The University of Bern, the University of Florida, the London School of Hygiene and Tropical Medicine, Public Health England, the European Mobile Laboratories among others. The trial was designed by a group of experts including the late Professor Donald A. Henderson of John Hopkins University, who led the WHO smallpox eradication effort by using the ring vaccination strategy. VSV-EBOV was developed by the Public Health Agency of Canada. The vaccine was licensed to NewLink Genetics, who in turn licensed it to Merck & Co. The vaccine works by replacing a gene from a harmless virus known as vesicular stomatitis virus:VSV with a gene encoding an Ebola virus surface protein. The vaccine does not contain any live Ebola virus. Earlier trials have shown the vaccine to be protective in animals, and be safe and produce an immune response in humans. Analysis only included cases occurring 10 days after receiving the vaccine to account for the incubation period of the Ebola virus.

Reference: Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial: Ana Maria Henao-Restrepo, MD; Prof Ira M Longini, PhD; Prof Matthias Egger, MD; Natalie E Dean, PhD; Prof W John Edmunds, PhD; Anton Camacho, PhD; Miles W Carroll, PhD; Moussa Doumbia, MD; Bertrand Draguez, MD; Sophie Duraffour, PhD; Godwin Enwere, FWACP; Rebecca Grais, PhD; Stephan Gunther, MD; Stefanie Hossmann, MSc; Prof Mandy Kader Kondé, PhD; Souleymane Kone, MSc; Eeva Kuisma, PhD; Prof Myron M Levine, MD; Sema Mandal, MD; Gunnstein Norheim, PhD; Ximena Riveros, BSc; Aboubacar Soumah, MD; Sven Trelle, MD; Andrea S Vicari, PhD; Conall H Watson, MFPH; Sakoba Kéïta, MD; Dr Marie Paule Kieny, PhD; Prof John-Arne Røttingen, MD: ω.

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Microbial Signatures in Child's Intestinal Microbiota Development May Link to Celiac Disease

Image of fecal bacteria community seen from microscopy and the bacterial DNA is stained by fluorescent:  Kuva: Pia Rasinkangas

|| December 09: 2016:  University of Helsinki: Jing Cheng and Eeva Karmitsa Writing || ά.   The interactions between a host and his:her microbiota have co-evolved over time and they exert profound effects on each other. Intestinal microbiota has been linked with a number of diseases, such as irritable bowel syndrome. However, the role of intestinal microbiota is unclear in celiac disease. In her doctoral thesis PhD Jing Cheng aimed to characterise the development and stability of intestinal microbiota in healthy young children and to compare the microbial features between children and adults. Furthermore, she investigated host-microbe interactions in celiac disease in healthy children and their counterparts with celiac disease.

To date, most efforts for detecting potential microbial changes affected by celiac disease have focused on adult individuals and have examined fecal materials, although it is known that early life is the critical period for the microbiota to colonize and establish their niche in the human intestine. At this time in healthy individuals, there is continuing cross-talk with the host e.g. via the immune system, leading to the establishment of homeostasis in both metabolic and immunological programming. Since the intestinal epithelium is the main interface for host, microbe interactions, the role of mucosa-associated microbiota may be distinct from that of fecal microbiota, but both the normal fluctuations in intestinal microbiota and the composition of duodenal mucosa-associated microbiota are still not fully clarified, explains Cheng.

The main findings of Cheng’s research showed that the intestinal microbiota of western children is not 'matured' until 5 years of age. The specific symbiotic microbial signatures called keystone species are developing towards adult-like microbial composition and abundance.

Moreover, Cheng observed differences between healthy and celiac disease associated microbial signatures. The differences may reflect changes in epithelial integrity associated with the celiac disease. She found out that specific symbiotic microbial signatures, keystone species, including important functional bacteria, may provide functional diagnostic or therapeutic targets for promoting healthy microbiota development.

Disturbed microbial signatures might contribute to the immunological balance in pediatric Celiac disease. Long term studies in a controlled environment with an adequate number of participants will be necessary to decode the disturbed microbial signature, concludes Cheng.

Researcher Jing Cheng, Ph.D, Doc. Reetta Satokari research group, Department of Veterinary Bioscience, University of Helsinki. Tel. 0452740616, Email: jing.cheng at helsinki.fi: E-thesis: https://helda.helsinki.fi/handle/10138/169508:ω.

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How Single-Celled Organisms Navigate to Oxygen

Colonies of choannaflagellates: Image: Raymond Goldstein

|| December 05: 2016: University of Cambridge News || ά. A team of researchers has discovered that tiny clusters of single-celled organisms that inhabit the world’s oceans and lakes, are capable of navigating their way to oxygen. Writing in e-Life scientists at the University of Cambridge describe how choanaflagellates, the closest relatives of animals, form small colonies that can sense a large range of concentrations of oxygen in the water. The research offers clues as to how these organisms evolved into multi-cellular ones.

Although the single-celled ancestors of animals are extinct, the choanoflagellates, which evolved from a common ancestor and which have remained single-celled since the Cambrian period around 500 million years ago, are common in the Earth’s oceans and lakes. Certain choanoflagellate species form small swimming colonies and these colonies are thought to resemble the early multicellular organisms that later evolved into animals. Oxygen levels on the planet started rising in the pre-Cambrian period and it’s likely this played a major influence on the emergence of these multicellular life forms.

The researchers observed choanoflagellate colonies swimming under controlled conditions and varied the oxygen concentration in the water over time. They found the colonies navigate based on the logarithm of the oxygen concentration, similar to the way humans sense sound and light. This increases their sensing capabilities in low-oxygen environments where navigation becomes crucial for survival.

One of the authors on the paper, Professor Raymond E. Goldstein, of the University’s Department of Applied Mathematics and Theoretical Physics, says, "Our work provides the first evidence that choanoflagellates can sense, and move towards, oxygen. Since choanoflagellates are now understood to be the closest relatives of animals, this discovery may shed light on the properties of the last common ancestor of the two groups, and in particular its response to the changing oxygen levels in the Precambrian era. Perhaps more importantly, the work raises fascinating questions about how the simplest multicellular organisms, lacking any type of central nervous system, sense and respond to their environment."

Many organisms find their way to favourable areas by using different strategies. Bacteria bias their tumbling to navigate towards food and algae can turn and move directly towards light. While choanaflagellates require oxygen, it wasn’t known if they could successfully navigate towards it. But the research showed both single cells and swimming colonies were able to find it.

While animals require enormous amounts of coordination between their cells in order to navigate, this research reveals such coordination isn’t needed for simple multicellular life forms. In addition, microorganisms’ search for food is rendered more difficult by the presence of thermal noise. Being so small, microorganisms are constantly being buffeted by vibrations in the waters that surround them, and their search strategy needs to be robust to counter this.

The team, based in the Department of Applied Mathematics and Theoretical Physics, included PhD student Julius B. Kirkegaard, visiting student Ambre Bouillant, postdoctoral fellow Dr. Alan O. Marron, Senior Research Associate Dr. Kyriacos C. Leptos, and Professor Raymond E. Goldstein.

This work was supported by the European Research Council, the Engineering and Physical Sciences Research Council, and the Wellcome Trust.

Reference: Kirkegaard, JB et al. Aerotaxis in the closest relatives of animals. e-Life; 24 Nov 2016; DOI: 10.7554/eLife.18109
 

:Creative Commons License: The text in this work of the University of Cambridge, is licensed under a Creative Commons Attribution 4.0 International License: ω.

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Giving Older Children Preventive Malaria Drugs Significantly Reduces Cases and Transmission

|| November 28: 2016: London School of Hygiene and Tropical Medicine News || ά.  Giving preventive antimalarial drugs to children up to age 10 during the high malaria season in Senegal more than halved cases of malaria in that age group, according to new research published in PLOS Medicine. The large randomised study of 200,000 children was led by the London School of Hygiene & Tropical Medicine and Université Cheikh Anta Diop, Senegal. It found Seasonal Malaria Chemoprevention:SMC also reduced cases in those above 10 years of age by a quarter, demonstrating that the intervention had contributed to reducing transmission of the disease.

SMC provides a high degree of personal protection but until now it was assumed that it would not contribute to community-wide reduction in the transmission of malaria. There were approximately 214 million malaria cases and an estimated 438,000 malaria deaths in 2015, 89% of cases and 91% of deaths occurred in Sub Saharan Africa. SMC is a relatively new tool in the fight against malaria. It involves treating children with antimalarial drugs sulfadoxine-pyrimethamine and amodiaquine once a month during the rainy season, to prevent malaria where the disease is highly seasonal.

Following a series of successful studies by the School and its partners in West Africa, the World Health Organisation recommended that children under five years of age living in the African Sahel and sub-Sahel should receive SMC. National malaria control programmes have been quick to respond and SMC has now been rolled out to 11 countries, reaching about 15 million children in 2016.

However, with the relative number of malaria cases in the region’s older children increasing, this new study was undertaken to examine the effectiveness of SMC extended to include children up to age 10. Between 2008 and 2011, 54 local health centres in central Senegal were randomised to provide SMC to children up to age 10, or act as controls. Over three years 780,000 SMC treatments were given to children. Malaria cases in each community were then monitored at outpatient clinics and hospitals, and deaths were recorded through surveys.

Dr Paul Milligan, lead investigator from the London School of Hygiene & Tropical Medicine, said: “Although progress is being made to tackle malaria, it remains one of the biggest killers of children in sub Saharan Africa. Seasonal Malaria Chemoprevention is designed specifically for situations where the malaria is intense but confined to a short period each year. We wanted to know if it was practical to include older children in SMC programmes, and discover what the subsequent effect on their health and malaria transmission would be.

“We found that SMC delivered by district health teams using community health workers reduced the incidence of malaria in the under 10s by 60% and the incidence of severe malaria by 45%. The intervention also led to a 26% decrease in cases of malaria in those above 10 years of age, showing that SMC could contribute to reducing malaria transmission. Although this effect was modest it is essential to winning the long-term fight against the disease. It is important now to strengthen national surveillance systems so we can define the regions where expanding the age range for SMC would have the greatest benefit.”

Importantly, the team found that including older children did not greatly increase the time needed to deliver the intervention each month. The treatments also provided a high degree of protection for an average cost of $0.50 per child each month and no severe side effects were recorded.

Dr Badara Cisse, lead investigator from the Université Cheikh Anta Diop, said: “The SMC intervention in Senegal is an example of a locally-adapted approach to malaria control that could be a blueprint for an effective strategy to tackle malaria in this part of Africa. The development of the SMC intervention illustrates the value of partnerships between researchers in endemic countries, malaria control programmes, and the London School of Hygiene & Tropical Medicine.”

The authors acknowledge limitations of the study, including the need to better understand the effect of SMC on antimalarial drug resistance and the fact that they weren’t able to demonstrate an effect on mortality.

However, since the study was completed, Senegal has started to introduce SMC for children up to 10 years of age as part of its national malaria control strategy. The monitoring and evaluation of this new programme includes assessments of drug safety and efficacy, and measuring the impact on malaria and child survival. The study was funded by the Bill & Melinda Gates Foundation.

Publication: Badara Cisse, El Hadj Ba, Cheikh Sokhna, Jean Louis NDiaye, Jules F. Gomis, Yankhoba Dial, Catherine Pitt, Mouhamed NDiaye, Matthew Cairns, Ernest Faye Magatte NDiaye, Aminata Lo, Roger Tine, Sylvain Faye, Babacar Faye, Ousmane Sy, Lansana Konate, Ekoue Kouevijdin, Clare Flach, Ousmane Faye, Jean-Francois Trape, Colin Sutherland, Fatou Ba Fall, Pape M. Thior, Oumar K. Faye, Brian Greenwood, Oumar Gaye, Paul Milligan. Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial. PLOS Medicine. DOI:10.1371/journal.pmed.1002175: ω.

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The Oncolytic Virus: A New Addition to the Weapons in the Fight Against Cancer

Metastatic hepatocellular carcinoma: Image: Yale Rosen

|| November 20: 2016: The Institute of Cancer Research London News || ά A virus that causes childhood coughs and colds could help in the fight against primary liver cancer, according to a new study. Reovirus stimulates the body’s own immune system to kill off the cancerous cells, the researchers based at the University of Leeds and The Institute of Cancer Research, London, found. In addition, Reovirus is able to kill off the hepatitis C virus, a common cause of primary liver cancer, at the same time, the team discovered.

These early-stage findings are important because primary liver cancer is the third highest cause of cancer deaths worldwide and, if surgery is not an option, the prognosis is poor. Study co-leader Dr Stephen Griffin, Associate Professor of Viral Oncology at the University of Leeds, said: “Ultimately we hope that by simultaneously treating the tumour, and the hepatitis virus that is driving the growth of the tumour, we may provide a more effective therapy and improve the outcomes for patients.

“Current treatments for liver cancer that can’t be removed by surgery are mainly palliative, with chemotherapy only tending to prolong life, rather than cure, and it can have significant side effects.” Reovirus can cause respiratory illnesses and stomach upsets in children but by adulthood most people have been exposed to it and therefore, it does not cause illness.

The team who conducted the research at the University of Leeds found that reovirus was successful in treating both liver cancer cells grown in the laboratory and those taken directly from patients undergoing surgery. Their study is published in the journal Gut. When introduced into the body, reovirus stimulates an immune system factor known as interferon, which in turn causes the activation of a specific white blood cell called a natural killer cell. These natural killer cells then kill both the tumour, and cells infected with the hepatitis C virus.

Stimulating the immune system to kill cancer cells is known as immunotherapy. It differs from chemotherapy, in which the actual drugs kill the cancer cells. The researchers are now hoping to start the first in-human clinical trials. Study co-leader Professor Alan Melcher, now Professor of Translational Immunotherapy at the Institute of Cancer Research, London, said: “Our study establishes a completely new type of viral immunotherapy for the most common primary liver cancer type, hepatocellular carcinoma, which has a very poor prognosis in its advanced form.

“Using a mixture of experiments in human cancer samples and mice, our research showed that the reovirus therapy switches on the host immune system to attack cancer cells, as well as suppressing the replication of hepatitis C virus, which is linked to many hepatocellular cancers. “We also showed that reovirus therapy could be used to treat a range of other cancer types associated with viral infection, including Epstein Barr Virus-associated lymphoma.”

Primary liver cancer is cancer that starts in the liver. It is a separate condition from secondary liver cancer, where the cancer originally developed in another part of the body and then spread to the liver. Most cases of primary liver cancer are associated with damage and scarring of the liver, most commonly from having a hepatitis B or hepatitis C viral infection. Less commonly it is caused by drinking excessive amounts of alcohol over many years.

At least 130 million people globally have chronic hepatitis C infection, according to the World Health Organisation, and a significant proportion of these will develop liver cancer. Co-researcher Dr Adel Samson from the University of Leeds said: “It is becoming increasingly clear that one of the most powerful weapons available to treat cancer is our own immune system.

However, as cancers are formed from our own cells, the immune system frequently struggles to identify the subtle differences that differentiate cancerous cells from normal cells, without help. Immunotherapy involves various strategies, such as a virus, as in our study, to kick-start our immune system to better identify and fight cancer. These ‘oncolytic’ viruses show great promise in clinical trials, and the first such virus has recently been licensed as a medicine for the treatment of skin cancer.”

Dr Justine Alford, Cancer Research UK’s senior science information officer, said: “This study in cells and mice suggests the possibility of using a harmless oncolytic virus as an immune-boosting one-two punch against liver cancer and the cancer-causing hepatitis C virus. “These early results also suggest this oncolytic virus could be used more widely in the treatment of virus-driven cancers.

In these cancers, the viruses can represent a major hurdle for treatment, so we urgently need new and effective ways to tackle the root of the problem. The next step will be to see if this technique will work in patients.” ω.

Enlighten Universana The Humanion Beacon Organisations: The Institute of Cancer Research London

Whatever Your Field of Work and Wherever in the World You are, Please, Make a Choice to Do All You Can to Seek and Demand the End of Death Penalty For It is Your Business What is Done in Your Name. The Law That Makes Humans Take Part in Taking Human Lives and That Permits and Kills Human Lives is No Law. It is the Rule of the Jungle Where Law Does Not Exist. The Humanion

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It's Time to Call in the Phage-Therapists

A lawn of bacteria into which bacteriophages have eaten holes by killing the bacteria they have infected. Kuva: M Skurnik Lab

 

|| November 19: 2016: University of Helsinki News: Päivi Lehtinen Writing || ά.  Phage therapy may be a solution to treating infections caused by antibiotic-resistant bacteria. Since 2013, researchers at the University of Helsinki in Finland have collected bacteriophages to combat antibiotic-resistant bacterial strains, and hope to start clinical phage therapy trials in the near future. “The first targets in the clinical trials of phage therapy could be, for example, wound infections or the eradication of antibiotic-resistant Escherichia coli bacteria from the intestine. Also acne could be considered as a target.” says Mikael Skurnik, from the University of Helsinki.

Bacteriophages or phages are viruses that kill bacteria. The most common organisms on the planet, they control the number of bacteria and maintain ecological balances in nature. Each bacteriophage infects only a few bacterial species or types, potentially making them real precision-guided ‘smart weapons’ in the battle against bacterial infections. “Unlike antibiotics, phages do not disturb the normal microbiota. And importantly, they can be used against antibiotic-resistant bacteria.” Skurnik adds. The first double-blind controlled clinical trials with phage therapy have recently been carried out in the United States, the United Kingdom and Belgium.

The trials have concentrated mainly on establishing the safety of the therapy. No adverse effects have been observed in these trials. The EU has also funded the PhagoBurn project where the efficacy of phage therapy using phage cocktails to treat burn wounds is being investigated. Phage therapy has not been used in patient care in Finland. Now, however, a new phage therapy project directed by Dr. Skurnik has received an €850,000 grant from the Jane and Aatos Erkko Foundation which will propel phage therapy towards its first clinical trials in Finland. The trials could focus on such antibioticresistant bacteria as Escherichia coli in the gut or MRSA on the skin. Acne could also be targeted.

The isolation and characterisation of phages takes place in the phage therapy laboratory at the University of Helsinki, where patient isolates will also be tested for phage sensitivity in order to identify appropriate phages for therapy. Clinical trials will be carried out at the Helsinki University Hospital, and a preparation line of phage therapy products will be set up in the Hospital pharmacy.

“The phage therapy products need to fulfil the drug quality requirements similar to other drugs.” professor Skurnik reminds. Phages for use against clinically relevant bacteria have been collected at both the University of Helsinki and University of Jyväskylä, and presently comprise close to 200 different phages.

“We are also discussing with other European phage scientists how to distribute phages between different laboratories in Europe. It could be possible if Europe had two or three central repositories for phages. These would receive phages from researchers, store and characterise them, and phage therapy laboratories in different countries could then order phages from the repositories.” says Skurnik.

Bacteriophages, bacteria eaters, were identified already in 1896 and were studied closely in the 1920s. At that time, phage therapy was used to treat both animal and human infections, such as cholera and bubonic plague, in India, often with good results.

In Western countries the invention of antibiotics ended scientists’ interest in phage therapy for several decades; however, this was not the case in Eastern Europe, especially in the former Soviet Union. The Eliava Institute in Tbilisi, Georgia, is still one of the most renowned phage therapy centres in the world. In the new millennium Western countries have realised the increasing threat of antibiotic resistance and a new interest in the potential use of phage therapy has emerged.

For further information: Professor Mikael Skurnik, University of Helsinki: Phone: +358 50 336 0981: E-mail: mikael.skurnik at helsinki.fi: ω.

Whatever Your Field of Work and Wherever in the World You are, Please, Make a Choice to Do All You Can to Seek and Demand the End of Death Penalty For It is Your Business What is Done in Your Name. The Law That Makes Humans Take Part in Taking Human Lives and That Permits and Kills Human Lives is No Law. It is the Rule of the Jungle Where Law Does Not Exist. The Humanion

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And What a Bacterium to Do: Help Humanity Keep Hold of the Carbon Dioxide That Wants to Escape

Bacteria could detect leaks at carbon capture sites: Unni Vik and Kjetill S. Jakobsen, at the University of Oslo, were part of the international team of researchers behind the new idea. Image: Bjarne Røsjø and University of Oslo


|| October 30: 2016: University of Oslo News || ά. Bacteria and archaea could be used to monitor stored carbon dioxide:CO2 and convert it into useful products, such as ethanol and acetate, say researchers at the Scottish Association for Marine Science:SAMS and the University of Oslo. In piece, published in Trends in Biotechnology, in early October they discuss how new bioinformatics tools would enable researchers to read shifts in microbial community genetics, making it possible to, for example, detect potential CO2 leaks, and how such analyses could contribute to making large-scale capture and storage of CO2 feasible.

Rising CO2 levels contribute to both global warming and ocean acidification. Capturing this CO2 from large point sources and storing it in underground geological formations, a process called carbon capture and storage:CCS, is considered one promising way to keep it out of the atmosphere and reduce its effects. The CO2 is buried in porous and permeable rock that is blanketed with at least one layer of impermeable rock. But this potential solution comes with risks.'' says Dr Natalie Hicks, a biogeochemist at SAMS. She continues, “One of the biggest concerns with carbon capture storage is the environmental impacts if there is a leak, …how would we know about it, how would we detect it, and what would the environmental implications be.”

Hicks and her co-authors, who include Kjetill S. Jakobsen and Unni Vik from the University of Oslo in a multidisciplinary team of geneticists and engineers, say that in addition to physical methods of monitoring CCS sites, such as measuring CO2 levels, which currently lack clear protocols and can be difficult at remote sites, it should be possible to monitor the bacteria and archaea living in sediment overlying these sites to detect potential leaks. They point to a simulated CO2 leak experiment previously conducted in a sub-seabed reservoir off the west coast of Scotland that detected changes in the microbial communities around the reservoir, before other organisms were visibly affected.

The researchers note that this approach will require more information on microbial communities and how they respond to fluctuations in CO2. It will also depend on the development of tools to sequence and analyse the genomic and metagenomics data in microbial communities, relate it to environmental conditions, and allow for the detection of small-scale changes in microbial response, such as a CO2 leak.

While there is a lot of work to be done to turn this microbial monitoring and utilisation of CO2 storage sites into a reality, the researchers believe it will be worth it. As Kjetill S. Jakobsen of the University of Oslo says, “There is a trade-off between risks and the necessity to control and to mediate CO2 and if you really have a huge problem like ocean acidification, you might have to use these techniques to get rid of it.”

Funding was provided by the COVERALL project, the Research Council of Norway, and the UK Engineering and Physical Sciences Research Council.

Author Contact: Dr Natalie Hicks: Natalie.Hicks at sams.ac.uk, +44 (0) 1631 559 440:office

Kjetill S Jakobsen, k.s.jakobsen at ibv.uio.no, +47-22854602:office: +47-90741779

Unni Vik: unni.vik at ibv.uio.no, +47-22854588

Trends in Biotechnology, published by Cell Press, is a monthly review journal of applied biosciences. It addresses what is new, significant, and practicable in the integrated use of many biological technologies from molecular genetics to biochemical engineering. ω.

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New Insight Into Course and Transmission of Zika Infection



This is a female Aedes aegypti mosquito: Not Aedes albopicturs: Image: UN Photo

|| October 24: 2016: BIDMC News: Boston: USA || ά. Though first documented 70 years ago, the Zika virus was poorly understood when it burst onto the scene in the Americas in 2015. In one of the first and largest studies of its kind, a research team lead by virologists at Beth Israel Deaconess Medical Centre:BIDMC has characterised the progression of two strains of the viral infection. The study, published online this week in Nature Medicine, revealed Zika’s rapid infection of the brain and nervous tissues, and provided evidence of risk for person-to-person transmission.

“We found, initially, that the virus replicated very rapidly and was cleared from the blood in most animals within ten days,” said corresponding author James B. Whitney, PhD, a principal investigator at the Centre for Virology and Vaccine Research:CVVR at BIDMC. “Nevertheless, we observed viral shedding in other bodily fluids such as spinal fluid, saliva, urine and semen, up to three weeks after the initial infection was already cleared.”

Whitney and colleagues infected 36 rhesus and cynomolgus macaques with strains of the Zika virus derived from Puerto Rico and Thailand. Over the next four weeks, the scientists tested blood, tissues, cerebrospinal fluid:CSF and mucosal secretions for the presence of Zika virus, as well as monitored the immune response during early infection. Their data shed new light on the previously little-studied virus, and might help explain how Zika causes the devastating neurological complications seen in adults and unborn babies.

“Of particular concern, we saw extraordinarily high levels of Zika virus in the brain of some of the animals, the cerebellum, specifically, soon after infection.” said Whitney, who is also assistant professor of medicine at Harvard Medical School and an associate member of the Ragon Institute of MGH, MIT, and Harvard. “Only one in five adults has noticeable symptoms of infection. However, if our data translate to humans, there may be need for enhanced clinical vigilance for any persons presenting with unusual neurological symptoms, and they should be tested for Zika infection.”

Like in humans, Zika infection in the experimental primates appeared relatively mild, producing fever and an increase in blood cells associated with the immune response. All recovered without intervention. But while the virus was cleared from the blood stream within ten days, the researchers observed Zika virus in urine as soon as two days after infection in some subjects. By the third day after infection, Zika was detectable in the saliva of up to half of the subjects, where it remained until the study ended at 28 days after infection.

“This underscores the need to understand what’s happening in anatomic reservoirs where the virus may hide for a long time.” said Whitney. Early in infection, the researchers found high levels of Zika in the genital tracts of both sexes. Zika remained detectable in semen and in uterine tissues until the end of the study. The first sexually transmitted case of Zika in humans was documented in 2007, but these new findings suggest transmission may occur long after Zika symptoms, if they ever appeared, resolve. Because the researchers found high levels of the virus in semen and uterus, but little in vaginal secretions, the findings may also illuminate sexual transmission of Zika.

“We found that male-to-female transmission may be easier, while female-to-male may be less likely.” said Whitney. “Nonetheless, the high levels of Zika we observed in the uterus underscore the danger to a developing fetus.”

The new study also highlights the need for the rapid development of vaccines and therapies against the virus. Zika infection in pregnant women has been shown to lead to fetal microcephaly and other major birth defects. The World Health Organisation declared the virus epidemic a global public health emergency on February 01, 2016.

Study coauthors include: co-first authors: Christa E. Osuna and So-Yun Lim, both of the CVVR at BIDMC; Claire Deleage of Leidos Biomedical Research at Frederick National Laboratory for Cancer Research,; Bryan D. Griffin, Derek Stein, Lukas T. Schroeder, Robert Omage, Ma Luo and co-first author, David Safronetz of the National Microbiology Laboratory, Canada; Katharine Best, Peter T. Hraber, Erwing Fabian Cardozo Ojeda and Alan S. Perelson of Los Alamos National Laboratory; Hanne Andersen-Elyard and co-first author Mark G. Lewis of Bioqual; Scott Huang, Dana L. Vanlandingham and Stephen Higgs of Biosecurity Research Institute, Kansas State University.

About Beth Israel Deaconess Medical Centre:BIDMC: Beth Israel Deaconess Medical Centre is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Centre and Hebrew Rehabilitation Centre and is a research partner of Dana-Farber:Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. ω.

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The Secret War of Staphylococcus Aureus Revealed

Professor Tracy Palmer: Image: University of Dundee

|| October 16: 2016: University of Dundee News || ά. Staphylococcus aureus, a bacterium that colonises approximately 30% of the human population at any one time, has now been shown to attack other bacteria, according to ground-breaking research from the University of Dundee. The bacterium which often inhabits the skin of humans and animals can cause a wide range of illnesses including minor skin infections to pneumonia, sepsis and toxic shock syndrome. Staphylococcus aureus is also one of the world’s most common causes of hospital-acquired infections.

The research, led by Professor Tracy Palmer, Head of the Division of Molecular Microbiology in the School of Life Sciences at the University, suggests that whilst Staphylococcus can live commensally on their human hosts, it possesses a dark side, secreting the toxin EsaD through its type VII secretion system to target competing strains. Victorious strains of Staphylococcus have been shown to contain both multiple variants of EsaD toxins as well as EsaG-like proteins which neutralise EasD and protect them from the toxic activity of competitors.

Professor Palmer said, “During our work we found that Staphylococcus secretes a large toxin which we think doesn’t target human cells but rather targets and kills other strains of Staphylococcus. This is exciting because it means they purposefully use their secretion system to compete with other strains, most likely for dominance in the human host.

“Colonising our bodies is the first step in the ability of Staphylococcus to cause disease. We believe this finding is just the tip of the iceberg, and we are now looking to find the entire toxin armoury and ultimately how it uses these toxins to colonise the body.” Recent analysis of over a thousand strains of Staphylococcus suggests that the toxins used in this ‘germ’ warfare were only present in half of them, yet all of those sequenced proved to contain the antitoxin, EsaG, which has now been shown to neutralise the aggressive toxin, EsaD.

This suggests that the strains are actively producing these proteins to target their rivals whilst also producing antitoxins to try and protect themselves. One strain had recently gained 11 copies of the antitoxin, suggesting that Staphylococcus is in a molecular arms race, probably to get a foothold on our bodies.

The research was funded by the Wellcome Trust, the Medical Research Council:MRC and the Biotechnology and Biological Sciences Research Council:BBSRC and has been published by the journal Nature Microbiology.

The study is part of wider research developed to help contribute to the fight against antimicrobial resistance, one of the major health problems facing the world today. 

The University of Dundee is the top ranked University in the UK for biological sciences, according to the 2014 Research Excellence Framework, the major survey of research quality in the UK.
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New Research Sheds Light on the Role of HPV in Head and Neck Cancers

Human Papillomavirus or HPV: Image: a work of the National Institutes of Health, part of the United States Department
of Health and Human Services. As a work of the U.S. federal government, the image is in the public domain

 

|| October 08: 2016: UCL News || ά. Human Papillomavirus:HPV drives a greater number of head and neck cancers than previously thought, finds new research from UCL and the University of Southampton. The findings, published in the Journal of Clinical Oncology, offer valuable insight into the role of HPV in