Shrink-wrapping spacesuits: Spacesuits of the future may resemble a streamlined second skin

For future astronauts, the process of suiting up may go something like this: Instead of climbing into a conventional, bulky, gas-pressurized suit, an astronaut may don a lightweight, stretchy garment, lined with tiny, musclelike coils. She would then plug in to a spacecraft's power supply, triggering the coils to contract and essentially shrink-wrap the garment around her body.

 The MIT BioSuit, a skintight spacesuit that offers improved mobility and reduced mass compared to modern gas-pressurized spacesuits.

The skintight, pressurized suit would not only support the astronaut, but would give her much more freedom to move during planetary exploration. To take the suit off, she would only have to apply modest force, returning the suit to its looser form.
Now MIT researchers are one step closer to engineering such an active, "second-skin" spacesuit: Dava Newman, a professor of aeronautics and astronautics and engineering systems at MIT, and her colleagues have engineered active compression garments that incorporate small, springlike coils that contract in response to heat. The coils are made from a shape-memory alloy (SMA) -- a type of material that "remembers" an engineered shape and, when bent or deformed, can spring back to this shape when heated.
The team incorporated the coils in a tourniquet-like cuff, and applied a current to generate heat. At a certain trigger temperature, the coils contract to their "remembered" form, such as a fully coiled spring, tightening the cuff in the process. In subsequent tests, the group found that the pressure produced by the coils equaled that required to fully support an astronaut in space.
"With conventional spacesuits, you're essentially in a balloon of gas that's providing you with the necessary one-third of an atmosphere [of pressure,] to keep you alive in the vacuum of space," says Newman, who has worked for the past decade to design a form-fitting, flexible spacesuit of the future. "We want to achieve that same pressurization, but through mechanical counterpressure -- applying the pressure directly to the skin, thus avoiding the gas pressure altogether. We combine passive elastics with active materials. … Ultimately, the big advantage is mobility, and a very lightweight suit for planetary exploration."
The coil design was conceived by Bradley Holschuh, a postdoc in Newman's lab. Holschuh and Newman, along with graduate student Edward Obropta, detail the design in the journal IEEE/ASME: Transactions on Mechatronics.
How to train a spacesuit
While skintight spacesuits have been proposed in the past, there's been one persistent design hurdle: how to squeeze in and out of a pressurized suit that's engineered to be extremely tight. That's where shape-memory alloys may provide a solution. Such materials only contract when heated, and can easily be stretched back to a looser shape when cool.
To find an active material that would be most suitable for use in space, Holschuh considered 14 types of shape-changing materials -- ranging from dielectric elastomers to shape-memory polymers -- before settling on nickel-titanium shape-memory alloys. When trained as tightly packed, small-diameter springs, this material contracts when heated to produce a significant amount of force, given its slight mass -- ideal for use in a lightweight compression garment.
The material is commonly produced in reels of very thin, straight fiber. To transform the fiber into coils, Holschuh borrowed a technique from another MIT group that previously used coiled nickel-titanium to engineer a heat-activated robotic worm.
Shape-memory alloys like nickel-titanium can essentially be "trained" to return to an original shape in response to a certain temperature. To train the material, Holschuh first wound raw SMA fiber into extremely tight, millimeter-diameter coils then heated the coils to 450 degrees Celsius to set them into an original, or "trained" shape. At room temperature, the coils may be stretched or bent, much like a paper clip. However, at a certain "trigger" temperature (in this case, as low as 60 C), the fiber will begin to spring back to its trained, tightly coiled state.
The researchers rigged an array of coils to an elastic cuff, attaching each coil to a small thread linked to the cuff. They then attached leads to the coils' opposite ends and applied a voltage, generating heat. Between 60 and 160 C, the coils contracted, pulling the attached threads, and tightening the cuff.
"These are basically self-closing buckles," Holschuh says. "Once you put the suit on, you can run a current through all these little features, and the suit will shrink-wrap you, and pull closed."
Keeping it tight
The group's next challenge is finding a way to keep the suit tight. To do this, Holschuh says there are only two options: either maintaining a constant, toasty temperature, or incorporating a locking mechanism to keep the coils from loosening. The first option would overheat an astronaut and require heavy battery packs -- a design that would significantly impede mobility, and is likely infeasible given the limited power resources available to astronauts in space. Holschuh and Newman are currently exploring the second option, looking into potential mechanisms to lock or clip the coils in place.
As for where the coils may be threaded within a spacesuit, Holschuh is contemplating several designs. For instance, an array of coils may be incorporated into the center of a suit, with each coil attached to a thread that radiates to the suit's extremities. As the coils activate, they could pull on the attached threads -- much like the strings of a puppet -- to tighten and pressurize the suit. Or, smaller arrays of coils could be placed in strategic locations within a spacesuit to produce localized tension and pressure, depending on where they are needed to maintain full body compression.
While the researchers are concentrating mostly on applications in space, Holschuh says the group's designs and active materials may be used for other purposes, such as in athletic wear or military uniforms.
"You could use this as a tourniquet system if someone is bleeding out on the battlefield," Holschuh says. "If your suit happens to have sensors, it could tourniquet you in the event of injury without you even having to think about it."
"An integrated suit is exciting to think about to enhance human performance," Newman adds. "We're trying to keep our astronauts alive, safe, and mobile, but these designs are not just for use in space."
This research was funded by NASA and the MIT Portugal Program.
 

Story Source:
The above story is based on materials provided by Massachusetts Institute of Technology. The original article was written by Jennifer Chu. Note: Materials may be edited for content and length.
 

Courtesy: ScienceDaily

 

 

Pathway that contributes to Alzheimer's disease revealed by research

Researchers at Jacksonville's campus of Mayo Clinic have discovered a defect in a key cell-signaling pathway they say contributes to both overproduction of toxic protein in the brains of Alzheimer's disease patients as well as loss of communication between neurons -- both significant contributors to this type of dementia.

Loss of LRP6 in neurons leads to enhanced buildup of amyloid protein, a pathological hallmark of Alzheimer's disease.

Their study, in the online issue of Neuron, offers the potential that targeting this specific defect with drugs "may rejuvenate or rescue this pathway," says the study's lead investigator, Guojun Bu, Ph.D., a neuroscientist at Mayo Clinic, Jacksonville, Fla.
"This defect is likely not the sole contributor to development of Alzheimer's disease, but our findings suggest it is very important, and could be therapeutically targeted to possibly prevent Alzheimer's or treat early disease," he says.
The pathway, Wnt signaling, is known to play a critical role in cell survival, embryonic development and synaptic activity -- the electrical and chemical signals necessary for learning and memory. Any imbalance in this pathway (too much or too little activity) leads to disease -- the overgrowth of cells in cancer is one example of overactivation of this pathway.
While much research on Wnt has focused on diseases involved in overactive Wnt signaling, Dr. Bu's team is one of the first to demonstrate the link between suppressed Wnt signaling and Alzheimer's disease.
"Our finding makes sense, because researchers have long known that patients with cancer are at reduced risk of developing Alzheimer's disease, and vice versa," Dr. Bu says. "What wasn't known is that Wnt signaling was involved in that dichotomy."
Using a new mouse model, the investigators discovered the key defect that leads to suppressed Wnt signaling in Alzheimer's. They found that the low-density lipoprotein receptor-related protein 6 (LRP6) is deficient, and that LRP6 regulates both production of amyloid beta, the protein that builds up in the brains of AD patients, and communication between neurons. That means lower than normal levels of LRP6 leads to a toxic buildup of amyloid and impairs the ability of neurons to talk to each other.
Mice without LRP6 had impaired Wnt signaling, cognitive impairment, neuroinflammation and excess amyloid.
The researchers validated their findings by examining postmortem brain tissue from Alzheimer's patients -- they found that LRP6 levels were deficient and Wnt signaling was severely compromised in the human brain they examined.
The good news is that specific inhibitors of this pathway are already being tested for cancer treatment. "Of course, we don't want to inhibit Wnt in people with Alzheimer's or at risk for the disease, but it may be possible to use the science invested in inhibiting Wnt to figure out how to boost activity in the pathway," Dr. Bu says.
"Identifying small molecule compounds to restore LRP6 and the Wnt pathway, without inducing side effects, may help prevent or treat Alzheimer's disease," he says. "This is a really exciting new strategy -- a new and fresh approach."
 

Journal Reference:

1. Chia-Chen Liu, Chih-Wei Tsai, Ferenc Deak, Justin Rogers, Michael Penuliar, You Me Sung, James N. Maher, Yuan Fu, Xia Li, Huaxi Xu, Steven Estus, Hyang-Sook Hoe, John D. Fryer, Takahisa Kanekiyo, Guojun Bu. Deficiency in LRP6-Mediated Wnt Signaling Contributes to Synaptic Abnormalities and Amyloid Pathology in Alzheimer’s Disease. Neuron, 2014; DOI: 10.1016/j.neuron.2014.08.048

Courtesy: ScienceDaily
 

Ebola outbreak 'out of all proportion' and severity cannot be predicted, expert says

  A mathematical model that replicates Ebola outbreaks can no longer be used to ascertain the eventual scale of the current epidemic, finds research conducted by the University of Warwick.

This image was captured in Monrovia, Liberia’s capital city, during the 2014 West African Ebola hemorrhagic fever (Ebola HF) outbreak that affected not only Liberia, but Sierra Leone, Guinea, and Nigeria as well.

Dr Thomas House, of the University’s Warwick Mathematics Institute, developed a model that incorporated data from past outbreaks that successfully replicated their eventual scale.
The research, titled "Epidemiological Dynamics of Ebola Outbreaks" and published by eLife, shows that when applying the available data from the ongoing 2014 outbreak to the model that it is, according to Dr House, “out of all proportion and on an unprecedented scale when compared to previous outbreaks”.
Dr House commented: “If we analyse the data from past outbreaks we are able to design a model that works for the recorded cases of the virus spreading and can successfully replicate their eventual size. The current outbreak does not fit this previous pattern and, as a result, we are not in a position to provide an accurate prediction of the current outbreak”.  
Chance events, Dr House argues, are an essential factor in the spread of Ebola and many other contagious diseases. “If we look at past Ebola outbreaks there is an identifiable way of predicting their overall size based on modelling chance events that are known to be important when the numbers of cases of infection are small and the spread is close to being controlled”.
Chance events can include a person’s location when they are most infectious, whether they are alone when ill, the travel patterns of those with whom they come into contact or whether they are close to adequate medical assistance.
The Warwick model successfully replicated the eventual scale of past outbreaks by analysing two key chance events: the initial number of people and the level of infectiousness once an epidemic is underway.
 “With the current situation we are seeing something that defies this previous pattern of outbreak severity. As the current outbreak becomes  more severe, it is less and less likely that it is a chance event and more likely that something more fundamental has changed”, says Dr House.
Discussing possible causes for the unprecedented nature of the current outbreak, Dr House argues that there could be a range of factors that lead it to be on a different scale to previous cases; “This could be as a result of a number of different factors: mutation of virus, changes in social contact patterns or some combination of these with other factors. It is implausible to explain the current situation solely through a particularly severe outbreak within the previously observed pattern”.
In light of the research findings and the United Nations calling for a further $1bn USD to tackle the current outbreak, Dr House says that “Since we are not in a position to quantify the eventful scale of this unprecedented outbreak, the conclusion from this study is not to be complacent but to mobilise resources to combat the disease.”
 

Journal Reference:

1. Thomas House. Epidemiological Dynamics of Ebola Outbreaks. eLife, 2014; 3 DOI: 10.7554/eLife.03908 

Courtesy: ScienceDaily
 

New single-dose influenza drug appears safe, effective

An analysis of phase 2 and phase 3 clinical trials shows that a single injected dose of the neuraminidase inhibitor (NAI) peramivir is safe and effective at alleviating influenza symptoms, including fever and viral shedding, when administered within 48 hours of the onset of symptoms. Researchers report their findings today at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), an infectious diseases meeting of the American Society for Microbiology (ASM).

"Based on clinical data, peramivir is the first neuraminidase inhibitor (NAI) that has shown to be safe and effective as a single-dose therapy for patients with acute, uncomplicated influenza. According to a retrospective combined analysis of two clinical studies, a single dose of peramivir, administered intramuscularly (IM), alleviated flu symptoms, including fever, significantly faster than the studies' placebo arms," says presenting author Rich Whitley of the University of Alabama at Birmingham.
In two placebo-controlled studies (one Phase II and one Phase III), involving a combined 427 adults, a single dose of peramivir was given as an injection within 48 hours of the onset of flu-like symptoms. Study participants recorded their temperature and the severity of seven flu symptoms using a four-point scale for 14 days. Peramivir was found to be generally safe and well tolerated and effectively reduced the duration of symptoms in peramivir-treated patients.
Compared to patients who received placebo, peramivir reduced median time to alleviation of symptoms by 22 hours, time to resolution of fever by 24 hours and the amount of nasal viral shedding over the first two days following treatment.
Influenza is a major public health problem. According to the Centers for Disease Control and Prevention, it is responsible for over 200,000 hospitalizations and 36,000 deaths annually in the United States. Vaccines can be effective in preventing influenza, but changing viral strains make vaccine formulation a challenge, and it is difficult to ensure broad populations are appropriately inoculated. Therefore, the CDC recommend antiviral treatment as soon as possible for any patient with confirmed or suspected influenza who is hospitalized, has severe, complicated or progressive illness or is at higher risk for complications. The two currently available NAIs -- oral oseltamivir and inhaled zanamivir -- are both administered twice daily for five days. At present, no single-dose or parenteral agent for treatment of influenza is available in the United States.
Peramivir has been approved in Japan and Korea since 2010, and it is estimated that 1 million Japanese patients have received drug post-approval. To date, more than 2,700 subjects have been treated with peramivir in 27 clinical trials. If approved by the FDA, peramivir would be the only single-dose and injection treatment for influenza in the U.S., and would be the first new NAI approved in more than a decade.
 

Story Source:
The above story is based on materials provided by American Society for Microbiology. Note: Materials may be edited for content and length.
 

 

courtesy: ScienceDaily

 

 

Targeting protein-making machinery to stop harmful bacteria

ne challenge in killing off harmful bacteria is that many of them develop a resistance to antibiotics. Researchers at the University of Rochester are targeting the formation of the protein-making machinery in those cells as a possible alternate way to stop the bacteria. And Professor of Biology Gloria Culver has, for the first time, isolated the middle-steps in the process that creates that machinery -- called the ribosomes.

"No one had a clear understanding of what happened inside an intact bacterial cell," said Culver, "And without that understanding, it would not be possible to block ribosome formation as a new means of stopping bacterial growth."
Since proteins are essential for life, organisms would die-off if not allowed to manufacture proteins.
Culver's work has been published in Nature Structural and Molecular Biology.
Ribosomes are made of ribonucleic acid (RNA) and protein molecules that fit together like pieces of a puzzle. In order for the puzzle to work, the strands of RNA molecules need to be pared down to the right size. This multi-step process happens very quickly, making it difficult to capture a piece of ribosomal RNA in one of the intermediate states. Culver and graduate student Neha Gupta have managed to do just that by using genetic tags as markers inside E. coli cells.
By attaching the tags to non-functional regions of the uncut RNA, the researchers were able to isolate the immature RNA strands during the various stages of processing.
On analyzing the intermediate fragments, Culver and Gupta found that ribosomal RNA does not follow a single sequential series of steps. While there appears to be an early common step, some of the intermediate RNA strands had started losing fragments from one side, while other intermediate RNAs at a similar stage were being cleaved from the other side. The different pathways of processing the RNA take place simultaneously among the various molecules, resulting in RNA strands being able to fit together with protein molecules to form fully-developed ribosomes.
Targeting ribosomes to kill drug-resistant bacteria is nothing new, except, in the past, scientists focused on mature ribosomes. While a range of antibiotics were developed to attack the ribosomes, the microbes eventually became resistant to those drugs.
While Culver's work creates new possibilities for stopping super-bugs, a great deal of work remains to be done.
"If bacterial cells have more than one way to make ribosomes, blocking just one pathway may not be enough to kill them." said Culver. "But our discoveries suggest that there is at least one common step that could be exploited to one day help scientists prevent the ribosomes from developing, which would kill off the bacteria."
 

Journal Reference:

1. Neha Gupta, Gloria M Culver. Multiple in vivo pathways for Escherichia coli small ribosomal subunit assembly occur on one pre-rRNA. Nature Structural & Molecular Biology, 2014; DOI: 10.1038/nsmb.2887 

 Courtesy: ScienceDaily

First international standards for growth of developing babies, size of newborns

The first international standards for fetal growth and newborn size have been developed by a global team led by scientists from Oxford University.

The standards depict the desirable pattern of healthy growth for all babies everywhere, regardless of their ethnicity or country of birth. They provide 3rd, 10th, 50th, 90th and 97th centile curves for the growth of a baby during pregnancy (as measured by ultrasound) and for a baby's size at birth according to gestational age (weight, length and head circumference).
Now, for the first time, all 120 million babies born each year across the world can be assessed using a common set of standards, reflecting how babies should grow when mothers have adequate health, nutrition, medical care and socioeconomic status.
This means it will be possible to detect underweight and overweight babies early in life no matter where in the world they are born.
'Being able to identify millions of additional undernourished babies at birth provides an opportunity for them to receive nutritional support and targeted treatment, without which close to 5% are likely to die in their first year or develop severe, long-term health problems,' says senior author Professor José Villar of Oxford University. 'The huge improvement in health care we can achieve is unprecedented.'
The international standards -- one for the growing fetus and the other for newborns -- are published in two papers in the medical journal The Lancet. They were developed as part of the landmark INTERGROWTH-21st Project, funded by the Bill & Melinda Gates Foundation, which took over 300 clinicians and researchers from 27 institutions across the world six years to complete.
Poor growth in the womb resulting in small size at birth is associated with illness and death in infancy and childhood. It also impacts on adult health with increased risks of diabetes, high blood pressure and cardiovascular disease. Smaller babies result in substantial costs for health services and they are a significant economic burden on society as a whole.
Being born overweight is also a worsening problem, particularly in developed and emerging countries, as a result of rising maternal obesity rates due to overnutrition. Overweight babies are at increased risk of diabetes and high blood pressure later in life.
At present, over 100 different, locally produced, growth charts are used around the world to assess fetal growth and newborn size. These only describe how babies grew in a particular population or region at a given time. International standards, on the other hand, describe what can be achieved with optimally healthy growth.
The researchers calculate that, each year, at least 13 million more newborns worldwide will be identified as being undernourished using their international standards. These babies are now considered 'normal', when local charts adapted for undernourished populations are used.
The INTERGROWTH-21st Project involved almost 60,000 pregnant women in eight well-defined urban areas in Brazil, China, India, Italy, Kenya, Oman, the UK and USA. From this very large number, over 4,600 healthy, well-nourished women with problem-free pregnancies were enrolled to construct the standards.
Ultrasound scans were performed every 5 weeks from early pregnancy (14 weeks' gestation) to delivery to generate the first international standards for fetal growth. Identical methods and the same ultrasound machines provided by Philips Healthcare were used in all countries.
Measurements of weight, length, and head circumference for more than 20,000 babies born between 33 and 42 weeks' gestation were used to generate the newborn standards.
This study design was the same approach taken by the WHO's Multicentre Growth Reference Study of healthy infants and children, which established the international WHO Child Growth Standards, from 0 to 5 years of age, that are now used in more than 140 countries worldwide.
Combining the WHO Child Growth Standards with the new fetal and newborn standards will provide health practitioners worldwide with clinical tools to monitor growth from early pregnancy to school.
'We have produced the first international standards describing how babies in the womb should grow when they are provided with good health care and nutrition, and are living in a healthy environment,' said Professor Stephen Kennedy of Oxford University, one of the senior authors of the study. 'We now need to work with politicians and clinicians at regional, national and international levels to introduce the new tools into practice around the world.'
Professor Zulfiqar Bhutta, from The Aga Khan University in Karachi, Pakistan, and the Hospital for Sick Children in Toronto, Chair of the INTERGROWTH-21st Project Steering Committee, said: 'These new standards for fetal growth and newborn size, and standardised methods for comparing length/height and head circumference for gestational age, are the best ways to compare populations across the globe. We hope their widespread use will contribute to improved birth outcomes and reduced perinatal mortality and morbidity worldwide. When combined with the existing WHO Child Growth Standards, it will be possible globally to make judgements on growth and size from early pregnancy to 5 years of age.'
Dr Julian Robinson of Harvard Medical School said: 'These are reliable tools to recognize inappropriate growth that can be applied to all the 120 million babies born every year in the world. In developed countries, introducing the standards will lead to more infants being diagnosed at birth as overweight and treated earlier to prevent chronic diseases later in life.'
The two Lancet papers follow the publication in July of two other papers from the INTERGROWTH-21st Project. The first in The Lancet Diabetes & Endocrinology showed that most of the variation in the average size of babies born in different places around the world is due to socioeconomic, healthcare and nutritional differences -- rather than ethnicity or country of birth. The second described a new international standard for dating pregnancy by ultrasound during the first trimester and was published in the journal Ultrasound in Obstetrics & Gynecology.
Together these papers provide a complete package of clinical tools for use worldwide in pregnancy and the neonatal period.
 

Journal References:

1. José Villar, Leila Cheikh Ismail, Cesar G Victora, Eric O Ohuma, Enrico Bertino, Doug G Altman, Ann Lambert, Aris T Papageorghiou, Maria Carvalho, Yasmin A Jaffer, Michael G Gravett, Manorama Purwar, Ihunnaya O Frederick, Alison J Noble, Ruyan Pang, Fernando C Barros, Cameron Chumlea, Zulfiqar A Bhutta, Stephen H Kennedy. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. The Lancet, 2014; 384 (9946): 857 DOI: 10.1016/S0140-6736(14)60932-6
2. Aris T Papageorghiou, Eric O Ohuma, Douglas G Altman, Tullia Todros, Leila Cheikh Ismail, Ann Lambert, Yasmin A Jaffer, Enrico Bertino, Michael G Gravett, Manorama Purwar, J Alison Noble, Ruyan Pang, Cesar G Victora, Fernando C Barros, Maria Carvalho, Laurent J Salomon, Zulfiqar A Bhutta, Stephen H Kennedy, José Villar. International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. The Lancet, 2014; 384 (9946): 869 DOI: 10.1016/S0140-6736(14)61490-2 

Courtesy: ScienceDaily
 

MERS: Low transmissibility, dangerous illness

The MERS coronavirus has caused disease outbreaks across the Arabian Peninsula and spread to Europe several times. The severe pneumonia virus has claimed the lives of several hundred people since its discovery in 2012. For a long time, scientists have been puzzled over how easily the pathogen spreads from human to human. An international team of researchers led by virologists from the University of Bonn have now come to the conclusion, through direct observation, that the rate of human transmission is low. Still, a third of infected persons with symptoms die. The results are now being presented in the New England Journal of Medicine.

Sebastian Brünink from the Institute of Virology at the University of Bonn Hospital prepares a test for detecting MERS infections.

The "Middle East Respiratory Syndrome Coronavirus" (MERS-CoV) was detected for the first time in 2012 on the Arabian Peninsula from where it spread to Europe and the USA, among other places. The virus causes severe acute lung infection. A total of at least 856 cases of illness have been registered in the meantime and at least 241 people have died. Scientists are puzzling over how infectious the disease is and how high the estimated number of unrecognized cases is. To date, there have been only theoretical projections.
For the first time, an international team of scientists led by Professor Christian Drosten at the Institute of Virology has been able to directly determine the rate of infection. "The transmissibility of the virus and the estimated number of unknown cases are low," says Prof. Drosten, summarizing the results. In Saudi Arabia, after new infections occurred, the researchers tracked how the disease spread further in the patients' home environments. A total of 280 people who lived in the households of 26 infected persons were examined. There was an infection in not more than twelve cases (four percent). "Since each infected person infected significantly fewer than one additional person, it can be assumed that the MERS virus will not cause a pandemic," concludes the virologist. A disease spreads rapidly only if each infected person infects several other people.
Along with people, dromedaries are an additional source of infection
However, the scientists say there is no reason for complacency: "Even if the rate of transmission is low: The MERS infection is very dangerous and about one-third of symptomatic patients die from the infection," says Prof. Drosten. Along with person-to-person infection, there is another important source: As a team of researchers working with Prof. Drosten published a year ago, dromedaries may be involved in transmission of the virus. They are widespread in the Middle East and could be responsible for a portion of human illnesses due to their close contact with people.
In the virologist's opinion, the fact that MERS infection rates significantly increase in the spring supports this hypothesis. At this time, there are many newborn camels and the one-year-old animals are separated from mothers which respectively causes an increased risk of infection. "Preventing an infection passed from animal to animal and then to people is not easy," says Prof. Drosten. One option would be to develop a MERS vaccine for camels. However, in the vast region of the Arab Peninsula vaccination coverage is logistically difficult to implement.
Virologists from the University of Bonn Hospital develop a new test
The virologists from the University of Bonn Hospital have for the first time developed a reliable method for detecting MERS infections in Saudi Arabian households. This method is used for the serological detection of antibodies in the blood. The new test is to be marketed soon by a German company and it will then be available to all physicians. Access to the families of infected persons in the Arabic country was a significant challenge for the international team of researchers from Germany, Saudi Arabia, the Netherlands and England. Dr. Ziad Memish, who was then the deputy Minister of Health in Saudi Arabia and senior author of the publication, helped convince people to be examined for the study.
 

Journal Reference:

1. Christian Drosten, Benjamin Meyer, Marcel A. Müller, Victor M. Corman, Malak Al-Masri, Raheela Hossain, Hosam Madani, Andrea Sieberg, Berend Jan Bosch, Erik Lattwein, Raafat F. Alhakeem, Abdullah M. Assiri, Waleed Hajomar, Ali M. Albarrak, Jaffar A. Al-Tawfiq, Alimuddin I. Zumla, Ziad A. Memish. Transmission of MERS-Coronavirus in Household Contacts. New England Journal of Medicine, 2014; 371 (9): 828 DOI: 10.1056/NEJMoa1405858 

Courtesy: ScienceDaily
 

 

Surprising discovery: HIV hides in gut, evading eradication

Researchers at UC Davis have made some surprising discoveries about the body's initial responses to HIV infection. Studying simian immunodeficiency virus (SIV), the team found that specialized cells in the intestine called Paneth cells are early responders to viral invasion and are the source of gut inflammation by producing a cytokine called interleukin-1 beta (IL-1β).

Though aimed at the presence of virus, IL-1β causes breakdown of the gut epithelium that provides a barrier to protect the body against pathogens. Importantly, this occurs prior to the wide spread viral infection and immune cell killing. But in an interesting twist, a beneficial bacterium, Lactobacillus plantarum, helps mitigate the virus-induced inflammatory response and protects gut epithelial barrier. The study was published in the journal PLoS Pathogens.
One of the biggest obstacles to complete viral eradication and immune recovery is the stable HIV reservoir in the gut. There is very little information about the early viral invasion and the establishment of the gut reservoir.
"We want to understand what enables the virus to invade the gut, cause inflammation and kill the immune cells," said Satya Dandekar, lead author of the study and chair of the Department of Medical Microbiology and Immunology at UC Davis.
"Our study has identified Paneth cells as initial virus sensors in the gut that may induce early gut inflammation, cause tissue damage and help spread the viral infection. Our findings provide potential targets and new biomarkers for intervening or blocking early spread of viral infection," she said.
In the study, the researchers detected a very small number of SIV infected cells in the gut within initial 2.5 days of viral infection; however, the inflammatory response to the virus was playing havoc with the gut lining. IL-1β was reducing the production of tight-junction proteins, which are crucial to making the intestinal barrier impermeable to pathogens. As a result, the normally cohesive barrier was breaking down.
Digging deeper, the researchers found the inflammatory response through IL-1β production was initiated in Paneth cells, which are known to protect the intestinal stem cells to replenish the epithelial lining. This is the first report of Paneth cell sensing of SIV infection and IL-1β production that links to gut epithelial damage during early viral invasion. In turn, the epithelial breakdown underscores that there's more to the immune response than immune cells.
"The epithelium is more than a physical barrier," said first author Lauren Hirao. "It's providing support to immune cells in their defense against viruses and bacteria."
The researchers found that addition of a specific probiotic strain, Lactobacillus plantarum, to the gut reversed the damage by rapidly reducing IL-1β, resolving inflammation, and accelerating repair within hours. The study points to interesting possibilities of harnessing synergistic host-microbe interactions to intervene early viral spread and gut inflammation and to mitigate intestinal complications associated with HIV infection.
"Understanding the players in the immune response will be important to develop new therapies," said Hirao. "Seeing how these events play out can help us find the most opportune moments to intervene."
 

Journal Reference:

1. Lauren A. Hirao, Irina Grishina, Olivier Bourry, William K. Hu, Monsicha Somrit, Sumathi Sankaran-Walters, Chris A. Gaulke, Anne N. Fenton, Jay A. Li, Robert W. Crawford, Frank Chuang, Ross Tarara, Maria L. Marco, Andreas J. Bäumler, Holland Cheng, Satya Dandekar. Early Mucosal Sensing of SIV Infection by Paneth Cells Induces IL-1β Production and Initiates Gut Epithelial Disruption. PLoS Pathogens, 2014; 10 (8): e1004311 DOI: 10.1371/journal.ppat.1004311 

Courtesy: ScienceDaily
 

Genomic sequencing reveals mutations, insights into 2014 Ebola outbreak

In response to an ongoing, unprecedented outbreak of Ebola virus disease (EVD) in West Africa, a team of researchers from the Broad Institute and Harvard University, in collaboration with the Sierra Leone Ministry of Health and Sanitation and researchers across institutions and continents, has rapidly sequenced and analyzed more than 99 Ebola virus genomes. Their findings could have important implications for rapid field diagnostic tests. The team reports its results online in the journal Science. 

 

Created by CDC microbiologist Frederick A. Murphy, this colorized transmission electron micrograph (TEM) revealed some of the ultrastructural morphology displayed by an Ebola virus virion.

For the current study, researchers sequenced 99 Ebola virus genomes collected from 78 patients diagnosed with Ebola in Sierra Leone during the first 24 days of the outbreak (a portion of the patients contributed samples more than once, allowing researchers a clearer view into how the virus can change in a single individual over the course of infection). The team found more than 300 genetic changes that make the 2014 Ebola virus genomes distinct from the viral genomes tied to previous Ebola outbreaks. They also found sequence variations indicating that, from the samples sequenced, the EVD outbreak started from a single introduction into humans, subsequently spreading from person to person over many months.

The variations they identified were frequently in regions of the genome encoding proteins. Some of the genetic variation detected in these studies may affect the primers (starting points for DNA synthesis) used in PCR-based diagnostic tests, emphasizing the importance of genomic surveillance and the need for vigilance. To accelerate response efforts, the research team released the full-length sequences on National Center for Biotechnology Information's (NCBI's) DNA sequence database in advance of publication, making these data available to the global scientific community.

"By making the data immediately available to the community, we hope to accelerate response efforts," said co-senior author Pardis Sabeti, a senior associate member at the Broad Institute and an associate professor at Harvard University. "Upon releasing our first batch of Ebola sequences in June, some of the world's leading epidemic specialists contacted us, and many of them are now also actively working on the data. We were honored and encouraged. A spirit of international and multidisciplinary collaboration is needed to quickly shed light on the ongoing outbreak."

The 2014 Zaire ebolavirus (EBOV) outbreak is unprecedented both in its size and in its emergence in multiple populated areas. Previous outbreaks had been localized mostly to sparsely populated regions of Middle Africa, with the largest outbreak in 1976 reporting 318 cases. The 2014 outbreak has manifested in the more densely-populated West Africa, and since it was first reported in Guinea in March 2014, 2,240 cases have been reported with 1,229 deaths (as of August 19).

Augustine Goba, Director of the Lassa Laboratory at the Kenema Government Hospital and a co-first author of the paper, identified the first Ebola virus disease case in Sierra Leone using PCR-based diagnostics. "We established surveillance for Ebola well ahead of the disease's spread into Sierra Leone and began retrospective screening for the disease on samples as far back as January of this year," said Goba. "This was possible because of our long-standing work to diagnose and study another deadly disease, Lassa fever. We could thus identify cases and trace the Ebola virus spread as soon as it entered our country."

The research team increased the amount of genomic data available on the Ebola virus by four fold and used the technique of "deep sequencing" on all available samples. Deep sequencing is sequencing done enough times to generate high confidence in the results. In this study, researchers sequenced at a depth of 2,000 times on average for each Ebola genome to get an extremely close-up view of the virus genomes from 78 patients. This high-resolution view allowed the team to detect multiple mutations that alter protein sequences -- potential targets for future diagnostics, vaccines, and therapies.

The Ebola strains responsible for the current outbreak likely have a common ancestor, dating back to the very first recorded outbreak in 1976. The researchers also traced the transmission path and evolutionary relationships of the samples, revealing that the lineage responsible for the current outbreak diverged from the Middle African version of the virus within the last ten years and spread from Guinea to Sierra Leone by 12 people who had attended the same funeral.

The team's catalog of 395 mutations (over 340 that distinguish the current outbreak from previous ones, and over 50 within the West African outbreak) may serve as a starting point for other research groups. "We've uncovered more than 300 genetic clues about what sets this outbreak apart from previous outbreaks," said Stephen Gire, a research scientist in the Sabeti lab at the Broad Institute and Harvard. "Although we don't know whether these differences are related to the severity of the current outbreak, by sharing these data with the research community, we hope to speed up our understanding of this epidemic and support global efforts to contain it."

"There is an extraordinary battle still ahead, and we have lost many friends and colleagues already like our good friend and colleague Dr. Humarr Khan, a co-senior author here," said Sabeti. "By providing this data to the research community immediately and demonstrating that transparency and partnership is one way we hope to honor Humarr's legacy. We are all in this fight together."

This work was supported by Common Fund and National Institute of Allergy and Infectious Diseases in the National Institutes of Health, Department of Health and Human Services, as well as by the National Science Foundation, the European Union Seventh Framework Programme, the World Bank, and the Natural Environment Research Council.

Other researchers who contributed to this work include Augustine Goba, Kristian G. Andersen, Rachel S. G. Sealfon, Daniel J. Park, Lansana Kanneh, Simbirie Jalloh, Mambu Momoh, Mohamed Fullah, Gytis Dudas, Shirlee Wohl, Lina M. Moses, Nathan L. Yozwiak, Sarah Winnicki, Christian B. Matranga, Christine M. Malboeuf, James Qu, Adrianne D. Gladden, Stephen F. Schaffner, Xiao Yang, Pan-Pan Jiang, Mahan Nekoui, Andres Colubri, Moinya Ruth Coomber, Mbalu Fonnie, Alex Moigboi, Michael Gbakie, Fatima K. Kamara, Veronica Tucker, Edwin Konuwa, Sidiki Saffa, Josephine Sellu, Abdul Azziz Jalloh, Alice Kovoma, James Koninga, Ibrahim Mustapha, Kandeh Kargbo, Momoh Foday, Mohamed Yillah, Franklyn Kanneh, Willie Robert, James L. B. Massally, Sinéad B. Chapman, James Bochicchio, Cheryl Murphy, Chad Nusbaum, Sarah Young, Bruce W. Birren, Donald S.Grant, John S. Scheiffelin, Eric S. Lander, Christian Happi, Sahr M. Gevao, Andreas Gnirke, Andrew Rambaut, Robert F. Garry, and S. Humarr Khan.

Journal Reference:

1. Gire, SK, Goba, A et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science, 2014 DOI: 10.1126/science.1259657

 Courtesy: ScienceDaily