The genetic evolution of Zika virus

An analysis comparing the individual differences between over 40 strains of Zika virus has identified significant changes in both amino acid and nucleotide sequences during the past half-century. The data support a strong divergence between the Asian and African lineages as well as human and mosquito isolates of the virus, and will likely be helpful as researchers flush out how a relatively unknown pathogen led to the current outbreak. 

This is a phylogenetic tree constructed from nucleotide data from 41 viral complete ORF sequences of ZIKV strains by the maximum likelihood-method logarithm in MEGA7 based on the Tamura-Nei model. A bootstrap percentage for 1,000 replicates was shown on the left. Branches corresponding to partitions reproduced in less than 70% of bootstrap replicates are not shown. Strains isolated from human, mosquito, and monkey (NIH reference strain) were labeled with blue, orange, and black circles, respectively. The two subtypes were labeled on the right side of the tree. The new strains Rio-U1 and Rio-S1 were highlighted using (*).

Credit: Wang and Valderramos et al./Cell Host & Microbe 2016

The project--led by researchers at the University of California, Los Angeles, and the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing--builds on other viral sequence analyses conducted over the past two months, with new large-scale and structural comparisons. Highlights of the findings include:

• All contemporary human Zika virus strains share a more similar sequence to the Malaysian/1966 strain than the Nigerian/1968 strain, suggesting the strains in the recent human outbreak evolved from the Asian lineage.
• All human strains identified in the 2015-2016 epidemic appear to be more closely related to the French Polynesia/2013 strain than the Micronesia/2007 strain, suggesting that the two variants evolved from a common ancestor.
• The prM (pre-membrane precursor) protein of the Zika virus had the highest percentage variability between the Asian human and the African mosquito subtypes, and modeling suggests that some of this variability contributes to a significant structural change.

"We believe these changes may, at least partially, explain why the virus has demonstrated the capacity to spread exponentially in the human population in the Americas," says senior study author Genhong Cheng, a professor in UCLA's Department of Microbiology, Immunology & Molecular Genetics. "These changes could enable the virus to replicate more efficiently, invade new tissues that provide protective niches for viral propagation, or evade the immune system, leading to viral persistence. Of course, all of these hypotheses will need to be tested in experimental models."
Future sequencing work will likely focus on understanding the Zika strain causing the 2015-2016 epidemic, which has yet to be isolated from a mosquito. Cheng's group and others will also begin to elucidate the structure of the viral proteins, which can inform drug and vaccine design. "We hope that our work provides a strong basis that will help the larger scientific community in accelerating Zika virus research," he says.
 

Journal Reference:

1. Wang and Valderramos et al. From Mosquitos to Humans: Genetic Evolution of Zika Virus. Cell Host & Microbe, April 2016 DOI: 10.1016/j.chom.2016.04.006 

Courtesy: ScienceDaily
 

Mothers' milk and the infant gut microbiota: An ancient symbiosis

Mothers' milk guides the development of neonates' gut microbiota, nourishing a very specific bacterial population that protects the child. Now a team of researchers has identified the compound in the milk that supplies this nourishment, and has shown that it can be obtained from cow's milk, which could result in using cow's milk as a prebiotic for infants. 

In earlier research, these investigators, led by David A. Mills, PhD, had shown that glycoproteins from milk, which contain both protein, and molecules containing multiple sugars, called oligosaccharides, were the source of that nourishment. They also had found that the infant-associated subspecies of the bacterium, Bifidobacterium longum subsp. infantis (B. infantis), produced an enzyme that could cleave the oligosaccharides from the milk glycoproteins, and they had identified that enzyme.
For the current study, Mills, who is Professor and Shields Endowed Chair in Dairy Food Science, and his collaborators posited that these oligosaccharides were the food source for B. infantis. They then showed that the enzyme could break down glycoproteins not only from mother's milk, but from cow's milk, releasing the oligosaccharides.
"The released oligosaccharides turned out to be an incredible substrate for B. infantis' growth," said Mills. At the same time, Mills et al. showed that the oligosaccharides did not nourish adult-associated bifidobacteria.
All that suggests that getting the bioactive oligosaccharides into infant formula could improve it, said Mills. But his emphasis is on the science, he said. "The amazing thing to me is how selective these released oligosaccharides are as a substrate for growth."
Mills noted that B. infantis has many genes involved in breaking down glycoproteins in mother's milk in order to release the oligosaccharides. Mother's milk coevolved over millions of years with mammals, and with their beneficial gut microbiota that it helped to thrive. "It is the only food that co-evolved with humans to make us healthy," said Mills.
 

Journal Reference:

1. Sercan Karav et al. Oligosaccharides released from milk glycoproteins are selective growth substrates for infant-associated bifidobacteria. Applied and Environmental Microbiology, April 2016 DOI: 10.1128/AEM.00547-16 

Courtesy: ScienceDaily
 

 

New hope for spinal cord injuries

Stem cells have been used successfully, for the first time, to promote regeneration after injury to a specialized band of nerve fibers that are important for motor function. 

CST axons entering into the graft (Green, graft; Red, CST axon).

Researchers from Hokkaido University in Japan together with an international team of scientists implanted specialized embryonic stem cells into the severed spinal cords of rats. The stem cells, called neural progenitor cells, were taken from rat embryos and directed to develop as spinal cord tissue. The implants, or "grafts," promoted extensive regeneration of the severed nerve fibres, with the rats showing improvement in their ability to move their forelimbs. The team also used grafts of human neural stem cells in injured rats with similar results, demonstrating the potential of the success of this method across species.
The corticospinal tract (CST) is a band of nerve fibres that travels from the brain, through the brain stem and into the spinal cord. This structure is very important for motor function in humans. Injuries to the CST can result in paralysis. Much research has been done, with some progress, on using stem cells to regenerate other bands of nerve fibres in the spinal cord. But these have involved small gaps between the severed nerves in the presence of bands of bridging tissue. Lesions to nerve fibres located in the CST, however, and those involving large gaps and no bands of bridging tissue have proven largely resistant to regeneration.
The success of this current trial, reported in Nature Medicine, is promising for the future treatment of humans with severe spinal cord injuries. But much work remains to be done before it can be translated into clinical treatments. Further research is required to determine the best cell type to be used for grafting and for establishing safe grafting methods.
 

Journal Reference:

1. Ken Kadoya, Paul Lu, Kenny Nguyen, Corinne Lee-Kubli, Hiromi Kumamaru, Lin Yao, Joshua Knackert, Gunnar Poplawski, Jennifer N Dulin, Hans Strobl, Yoshio Takashima, Jeremy Biane, James Conner, Su-Chun Zhang, Mark H Tuszynski. Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Nature Medicine, 2016; DOI: 10.1038/nm.4066 

Courtesy: ScienceDaily
 

Scientists store digital images in DNA, and retrieves them perfectly

Researchers have developed one of the first complete systems to store digital data in DNA -- allowing companies to store data that today would fill a big box store supercenter in a space the size of a sugar cube. 

ll the movies, images, emails and other digital data from more than 600 basic smartphones (10,000 gigabytes) can be stored in the faint pink smear of DNA at the end of this test tube.

But a new technique developed by University of Washington and Microsoft researchers could shrink the space needed to store digital data that today would fill a Walmart supercenter down to the size of a sugar cube.
The team of computer scientists and electrical engineers has detailed one of the first complete systems to encode, store and retrieve digital data using DNA molecules, which can store information millions of times more compactly than current archival technologies.
In one experiment outlined in a paper presented in April at the ACM International Conference on Architectural Support for Programming Languages and Operating Systems, the team successfully encoded digital data from four image files into the nucleotide sequences of synthetic DNA snippets.
More significantly, they were also able to reverse that process -- retrieving the correct sequences from a larger pool of DNA and reconstructing the images without losing a single byte of information.
The team has also encoded and retrieved data that authenticates archival video files from the UW's Voices from the Rwanda Tribunal project that contain interviews with judges, lawyers and other personnel from the Rwandan war crime tribunal.
"Life has produced this fantastic molecule called DNA that efficiently stores all kinds of information about your genes and how a living system works -- it's very, very compact and very durable," said co-author Luis Ceze, UW associate professor of computer science and engineering.
"We're essentially repurposing it to store digital data -- pictures, videos, documents -- in a manageable way for hundreds or thousands of years."
The digital universe -- all the data contained in our computer files, historic archives, movies, photo collections and the exploding volume of digital information collected by businesses and devices worldwide -- is expected to hit 44 trillion gigabytes by 2020.
That's a tenfold increase compared to 2013, and will represent enough data to fill more than six stacks of computer tablets stretching to the moon. While not all of that information needs to be saved, the world is producing data faster than the capacity to store it.
DNA molecules can store information many millions of times more densely than existing technologies for digital storage -- flash drives, hard drives, magnetic and optical media. Those systems also degrade after a few years or decades, while DNA can reliably preserve information for centuries. DNA is best suited for archival applications, rather than instances where files need to be accessed immediately.
The team from the Molecular Information Systems Lab housed in the UW Electrical Engineering Building, in close collaboration with Microsoft Research, is developing a DNA-based storage system that it expects could address the world's needs for archival storage.
First, the researchers developed a novel approach to convert the long strings of ones and zeroes in digital data into the four basic building blocks of DNA sequences -- adenine, guanine, cytosine and thymine.
"How you go from ones and zeroes to As, Gs, Cs and Ts really matters because if you use a smart approach, you can make it very dense and you don't get a lot of errors," said co-author Georg Seelig, a UW associate professor of electrical engineering and of computer science and engineering. "If you do it wrong, you get a lot of mistakes."
The digital data is chopped into pieces and stored by synthesizing a massive number of tiny DNA molecules, which can be dehydrated or otherwise preserved for long-term storage.
The UW and Microsoft researchers are one of two teams nationwide that have also demonstrated the ability to perform "random access" -- to identify and retrieve the correct sequences from this large pool of random DNA molecules, which is a task similar to reassembling one chapter of a story from a library of torn books.
To access the stored data later, the researchers also encode the equivalent of zip codes and street addresses into the DNA sequences. Using Polymerase Chain Reaction (PCR) techniques -- commonly used in molecular biology -- helps them more easily identify the zip codes they are looking for. Using DNA sequencing techniques, the researchers can then "read" the data and convert them back to a video, image or document file by using the street addresses to reorder the data.
Currently, the largest barrier to viable DNA storage is the cost and efficiency with which DNA can be synthesized (or manufactured) and sequenced (or read) on a large scale. But researchers say there's no technical barrier to achieving those gains if the right incentives are in place.
Advances in DNA storage rely on techniques pioneered by the biotechnology industry, but also incorporate new expertise. The team's encoding approach, for instance, borrows from error correction schemes commonly used in computer memory -- which hadn't been applied to DNA.
"This is an example where we're borrowing something from nature -- DNA -- to store information. But we're using something we know from computers -- how to correct memory errors -- and applying that back to nature," said Ceze.
"This multidisciplinary approach is what makes this project exciting. We are drawing from a diverse set of disciplines to push the boundaries of what can be done with DNA. And, as a result, creating a storage system with unprecedented density and durability," said Karin Strauss, a researcher at Microsoft and UW affiliate associate professor of computer science and engineering.
The research was funded by Microsoft Research, the National Science Foundation, and the David Notkin Endowed Graduate Fellowship.
Co-authors include UW computer science and engineering doctoral student James Bornholt, UW bioengineering doctoral student Randolph Lopez and Douglas Carmean, a partner architect at Microsoft Research and a UW affiliate professor of computer science and engineering.
 

Story Source:
The above post is reprinted from materials provided by University of Washington. The original item was written by Jennifer Langston. Note: Materials may be edited for content and length.
 

Courtesy: ScienceDaily

 

Fresh fruit associated with lower risk of heart attack and stroke

People who eat fresh fruit on most days are at lower risk of heart attack and stroke than people who rarely eat fresh fruit, according to new research. The findings come from a seven-year study of half a million adults in China, where fresh fruit consumption is much lower than in countries like the UK or US. 

Researchers from the University of Oxford and Chinese Academy of Medical Sciences conducted a large, nationwide study of 500,000 adults from 10 urban and rural localities across China, tracking health for 7 years through death records and electronic hospital records of illness. The present study was among people who did not have a history of cardiovascular diseases or anti-hypertensive treatments when first joined the study.
Fruit is a rich source of potassium, dietary fiber, antioxidants, and various other potentially active compounds, and contains little sodium or fat and relatively few calories. The study found that fruit consumption (which was mainly apples or oranges) was strongly associated with many other factors, such as education, lower blood pressure, lower blood glucose, and not smoking. But, after allowing for what was known of these and other factors, a 100g portion of fruit per day was associated with about one-third less cardiovascular mortality and the association was similar across different study areas and in both men and women.
Study author Dr Huaidong Du, University of Oxford, UK, said "The association between fruit consumption and cardiovascular risk seems to be stronger in China, where many still eat little fruit, than in high-income countries where daily consumption of fruit is more common." Also, fruit in China is almost exclusively consumed raw, whereas much of the fruit in high-income countries is processed, and many previous studies combined fresh and processed fruit.
Co-author Professor Liming Li, Chinese Academy of Medical Sciences, said "A recent Global Burden of Disease report put low fruit consumption as one of the leading causes of premature death in China. However, this was based on little evidence from China itself."
The senior author, Professor Zhengming Chen, University of Oxford, UK, said "It's difficult to know whether the lower risk in people who eat more fresh fruit is because of a real protective effect. If it is, then widespread consumption of fresh fruit in China could prevent about half a million cardiovascular deaths a year, including 200,000 before age 70, and even larger numbers of non-fatal strokes and heart attacks."

Journal Reference:

1. Huaidong Du, Liming Li, Derrick Bennett, Yu Guo, Timothy J. Key, Zheng Bian, Paul Sherliker, Haiyan Gao, Yiping Chen, Ling Yang, Junshi Chen, Shanqing Wang, Ranran Du, Hua Su, Rory Collins, Richard Peto, Zhengming Chen. Fresh Fruit Consumption and Major Cardiovascular Disease in China. New England Journal of Medicine, 2016; 374 (14): 1332 DOI: 10.1056/NEJMoa1501451

Courtesy: ScienceDaily

US doctors report reconstructing new esophagus tissue in a critically ill patient

merican doctors report the first case of a human patient whose severely damaged esophagus was reconstructed using commercially available FDA approved stents and skin tissue. Seven years after the reconstruction and four years after the stents were removed, the patient continues to eat a normal diet and maintain his weight with no swallowing problems. 

he esophagus is a hollow muscular tube that connects the mouth to the stomach carrying food and liquids. Removal of the esophagus (esophagectomy) to treat cancer or injury requires reconnecting the remaining part of the esophagus to the stomach to allow swallowing and the passage of food.

Until now, this regeneration technique has only been tested in animals. The authors, reporting on the outcome of the procedure, say that research, including animal studies and clinical trials, are now needed to investigate whether the technique can be reproduced and used in other similar cases.
Professor Kulwinder Dua from the Medical College of Wisconsin, Milwaukee, USA, and colleagues report using metal stents as a non-biological scaffold and a regenerative tissue matrix from donated human skin to rebuild a full-thickness 5cm defect in the esophagus of a 24-year-old man. The patient was urgently admitted to hospital with a disrupted esophagus resulting in life-threatening infection and inability to swallow following complications from an earlier car accident which had left him partially paralysed. Despite several surgeries, the defect in the esophagus was too large to repair.
The esophagus is a hollow muscular tube that connects the mouth to the stomach carrying food and liquids. Removal of the esophagus (esophagectomy) to treat cancer or injury requires reconnecting the remaining part of the esophagus to the stomach to allow swallowing and the passage of food. Part of the stomach or colon is used to make this connection. However, the procedure was not possible in this case because the defect in the esophagus was too large, and the patient too ill to undergo the procedure.
The team hypothesized that if the three-dimensional shape of the esophagus could be maintained in its natural environment for an extended period of time while stimulating regeneration using techniques previously validated in animals, esophageal reconstruction may be possible.
They used commercially available, FDA-approved, materials to repair the defect. To maintain the shape of the esophagus and bridge the large defect, they used an endoscope to place self-expanding metal stents. The defect was then surgically covered with regenerative tissue matrix and sprayed with a platelet-rich plasma gel produced from the patient's own blood to deliver high concentrations of growth factors that not only stimulate growth but also attract stem cells to stimulate healing and regeneration. The sternocleidomastoid, a muscle running along the side of the neck, was placed over the matrix and the adhesive platelet-rich plasma gel.
The team planned on removing the stent 12 weeks after reconstruction, but the patient delayed the procedure for three and a half years because of fears of developing a narrowing or leakage in the esophagus. One year after the stents were removed, endoscopic ultrasound images showed areas of fibrosis (scarring) and regeneration of all five layers of the esophageal wall. Full recovery of functioning was also established by swallowing tests showing that esophageal muscles were able to propel water and liquid along the esophagus into the stomach in both upright and 45° sitting positions. But, how long the regeneration process took is unclear because the patient delayed stent removal for several years.
According to Professor Dua, "This is a first in human operation and one that we undertook as a life-saving measure once we had exhausted all other options available to us and the patient. The use of this procedure in routine clinical care is still a long way off as it requires rigorous assessment in large animal studies and phase 1 and 2 clinical trials. The approach we used is novel because we used commercially available products which are already approved for use in in the human body and hence didn't require complex tissue engineering."

Journal Reference:

1. Mario Gasparri, MD et al. In-vivo oesophageal regeneration in a human being by use of a non-biological scaffold and extracellular matrix. The Lancet, April 2016 DOI: 10.1016/S0140-6736(15)01036-3

Courtesy: ScienceDaily