Sunlight offers surprise benefit: It energizes infection fighting T cells

Sunlight, through a mechanism separate than vitamin D production, energizes T cells that play a central role in human immunity, researchers have found. The findings suggest how the skin, the body’s largest organ, stays alert to the many microbes that can nest there.

Georgetown University Medical Center researchers have found that sunlight, through a mechanism separate than vitamin D production, energizes T cells that play a central role in human immunity.
Their findings, published today in Scientific Reports, suggest how the skin, the body's largest organ, stays alert to the many microbes that can nest there.
"We all know sunlight provides vitamin D, which is suggested to have an impact on immunity, among other things. But what we found is a completely separate role of sunlight on immunity," says the study's senior investigator, Gerard Ahern, PhD, associate professor in the Georgetown's Department of Pharmacology and Physiology. "Some of the roles attributed to vitamin D on immunity may be due to this new mechanism."
They specifically found that low levels of blue light, found in sun rays, makes T cells move faster -- marking the first reported human cell responding to sunlight by speeding its pace.
"T cells, whether they are helper or killer, need to move to do their work, which is to get to the site of an infection and orchestrate a response," Ahern says. "This study shows that sunlight directly activates key immune cells by increasing their movement."
Ahern also added that while production of vitamin D required UV light, which can promote skin cancer and melanoma, blue light from the sun, as well as from special lamps, is safer.
And while the human and T cells they studied in the laboratory were not specifically skin T cells -- they were isolated from mouse cell culture and from human blood -- the skin has a large share of T cells in humans, he says, approximately twice the number circulating in the blood.
"We know that blue light can reach the dermis, the second layer of the skin, and that those T cells can move throughout the body," he says.
The researchers further decoded how blue light makes T cells move more by tracing the molecular pathway activated by the light.
What drove the motility response in T cells was synthesis of hydrogen peroxide, which then activated a signaling pathway that increases T cell movement. Hydrogen peroxide is a compound that white blood cells release when they sense an infection in order to kill bacteria and to "call" T cells and other immune cells to mount an immune response.
"We found that sunlight makes hydrogen peroxide in T cells, which makes the cells move. And we know that an immune response also uses hydrogen peroxide to make T cells move to the damage," Ahern says. "This all fits together."
Ahern says there is much work to do to understand the impact of these findings, but he suggests that if blue light T cell activation has only beneficial responses, it might make sense to offer patients blue light therapy to boost their immunity.
 

Journal Reference:

1. Thieu X. Phan, Barbara Jaruga, Sandeep C. Pingle, Bidhan C. Bandyopadhyay, Gerard P. Ahern. Intrinsic Photosensitivity Enhances Motility of T Lymphocytes. Scientific Reports, 2016; 6: 39479 DOI: 10.1038/srep39479 

Courtesy: ScienceDaily
 

Case for sexual transmission of Zika virus strengthened

Aedes aegypti mosquitoes harboring parasitic Zika virus (ZIKV) are the primary transmitters of virus to humans, potentially causing catastrophic congenital microcephaly in babies born to women bitten by infected mosquitoes. But confirmation earlier this year that ZIKV can also be sexually transmitted raised new alarm that virus could be passed between sexual partners in venues far from mosquito habitats.

Although Zika is primarily thought of as mosquito-borne illness, sexual transmission plays an important role in the spread of the virus. Weeks or even months after the virus has been cleared from the bloodstream, Zika can still be found in semen and transmitted through sexual contact. Women can pass the virus to their unborn babies during pregnancy.

Credit: Dr. Kenneth Kim and Dr. Gina Kirchweger, La Jolla Institute for Allergy and Immunology

Now La Jolla Institute for Allergy & Immunology (LJI) investigator Sujan Shresta, Ph.D., employs two different mouse models to confirm that live ZIKV placed directly in the vagina infects the mouse's reproductive tract, replicates, moves into the bloodstream, and causes clinical signs of disease. Intriguingly, that study published in the December 20, 2016 issue of Cell Reports, also reports that the stage of the reproductive cycle during which a female mouse is exposed to virus determines vulnerability to infection. If applicable to humans, this discovery has public health implications for virus transmission to a population of great concern, women of child-bearing age.
"Currently, almost all of our efforts in terms of Zika prevention focus on mosquito control," says Shresta, an associate professor in LJI's Center for Infectious Disease. "Our new work begs clinicians to also address whether sexual transmission of the virus constitutes a small or large proportion of cases."
Investigators knew that virus hides in semen of men who contract ZIKV from mosquitoes and that virus is transmitted vaginally in rodent models. But the biological questions -- what cells are infected, how stable the virus is in bodily fluids -- were unanswered. Shresta's group began to explore them by placing live ZIKV in the vaginas of female mice that had been genetically engineered to be immunocompromised.
But before the procedure, they treated mice with hormones to create two groups that differed with regard to where they were in their menstrual cycle. Dramatic differences emerged post-infection: mice infected in the diestrus or in between phase became progressively sick, lost weight, and died in 2-3 weeks, as one might predict in these mice. Remarkably, the same strain of immunocompromised AG129 mice infected in estrus phase showed no sign of disease.
William Weihao Tang, the study's first author, calls this one the paper's most intriguing findings. "The strain of mice we used, called AG129, were originally engineered to be extremely vulnerable to infection," he says. "But even these mice, when infected in estrus phase, appeared completely resistant to virus. That surprised us."
Shresta says that a caveat is that responses in mouse strains like AG129, which were purposely engineered to serve as a "lethal" model of infection, must be tested in mice with greater immune function. "For science to be relevant to humans, we always confirm results in the most 'immunocompetent' mouse that better reflects a normal human immune system."
To do that, her team repeated experiments in an entirely different type of engineered mouse, one only moderately susceptible to infection, which scientists call a "non-lethal" model. When infected in diestrus phase, those mice lost weight and exhibited clinical signs of disease but, unlike their AG129 counterparts, eventually recovered. However, just like the AG129 mice, when infected in estrus phase "non-lethal" mice showed no sign of Zika-like disease.
This trend was reflected in other experimental outcomes. For example, in both lethal and non-lethal strains, viral RNA, which serves as direct evidence of virus, persisted in the vaginal canal sometimes as long as 10 days post-infection in diestrus. By contrast, viral RNA disappeared three days after infection in estrus phase.
Virus persistence in vaginal fluids may account for why diestrus-infected mice become sick, regardless of mouse strain, yet the molecular or cellular basis for susceptibility remains unclear. Mice analyzed in the study were experimentally synchronized or "staged" at one of two reproductive phases by hormonal injection, which may provide a clue. "Hormones changed the mouse female reproductive tract in ways that either enhanced or protected against sexual transmission," says Tang, although he and Shresta caution it is much too early to generalize mouse findings to humans.
But if similar mechanisms prove relevant to human transmission, they are cause for concern, largely because most Zika-infected men or women show few or no symptoms. Thus they could unwittingly engage in sexual activity resulting in adult disease or even in utero transfer of virus to an unborn child.
Recent CDC "case counts" suggest that thus far that few Zika cases in the US were likely transmitted sexually. But these numbers are estimates, and sexual transmission of ZIKV is taken extremely seriously in other regions, such as South America. In fact, one mathematical modeling study of Baranquilla, Colombia, estimated that as many as 47% of Zika cases reported there emerged from sexual contact.
"In humans sexual transmission may be a bigger deal than has been thought," says Shresta, emphasizing that currently we know very little about this mode of Zika transmission. "We know that in males virus can remain in semen for possibly months, while a man shows no symptoms. During that time he could unknowingly pass it to a sexual partner."
The next step for the Shresta lab is to take advantage of these two mouse models to define immune signals that make mice susceptible to or protected from ZIKV infection. "We are ultimately interested in drugs or vaccines to prevent the disease," says Shresta, who has also used immunodeficient mice as models to study dengue virus infection. "Being able to test interventions in two animal models, one that succumbs to infection and another that recovers, is a plus. Developing vaccines requires access to models representing all scenarios."
 

Journal Reference:

1. William Weihao Tang, Matthew Perry Young, Anila Mamidi, Jose Angel Regla-Nava, Kenneth Kim, Sujan Shresta. A Mouse Model of Zika Virus Sexual Transmission and Vaginal Viral Replication. Cell Reports, 2016; 17 (12): 3091 DOI: 10.1016/j.celrep.2016.11.070 

Courtesy: ScienceDaily
 

Helping pays off: People who care for others live longer

Older people who help and support others live longer, a new study has concluded. The results of these findings show that this kind of caregiving can have a positive effect on the mortality of the carers. 

Older people who help and support others are also doing themselves a favor. An international research team has found that grandparents who care for their grandchildren on average live longer than grandparents who do not. The researchers conducted survival analyses of over 500 people aged between 70 and 103 years, drawing on data from the Berlin Aging Study collected between 1990 and 2009.
In contrast to most previous studies on the topic, the researchers deliberately did not include grandparents who were primary or custodial caregivers. Instead, they compared grandparents who provided occasional childcare with grandparents who did not, as well as with older adults who did not have children or grandchildren but who provided care for others in their social network.
Emotional support
The results of their analyses show that this kind of caregiving can have a positive effect on the mortality of the carers. Half of the grandparents who took care of their grandchildren were still alive about ten years after the first interview in 1990. The same applied to participants who did not have grandchildren, but who supported their children -- for example, by helping with housework. In contrast, about half of those who did not help others died within five years.
The researchers were also able to show that this positive effect of caregiving on mortality was not limited to help and caregiving within the family. The data analysis showed that childless older adults who provided others with emotional support, for example, also benefited. Half of these helpers lived for another seven years, whereas non-helpers on average lived for only another four years.
Too intense involvement causes stress
"But helping shouldn't be misunderstood as a panacea for a longer life," says Ralph Hertwig, Director of the Center for Adaptive Rationality at the Max Planck Institute for Human Development. "A moderate level of caregiving involvement does seem to have positive effects on health. But previous studies have shown that more intense involvement causes stress, which has negative effects on physical and mental health," says Hertwig. As it is not customary for grandparents in Germany and Switzerland to take custodial care of their grandchildren, primary and custodial caregivers were not included in the analyses.
The researchers think that prosocial behavior was originally rooted in the family. "It seems plausible that the development of parents' and grandparents' prosocial behavior toward their kin left its imprint on the human body in terms of a neural and hormonal system that subsequently laid the foundation for the evolution of cooperation and altruistic behavior towards non-kin," says first author Sonja Hilbrand, doctoral student in the Department of Psychology at the University of Basel.
 

ournal Reference:

1. Sonja Hilbrand, David A. Coall, Denis Gerstorf, Ralph Hertwig. Caregiving within and beyond the family is associated with lower mortality for the caregiver: A prospective study. Evolution and Human Behavior, 2016; DOI: 10.1016/j.evolhumbehav.2016.11.010 

Courtesy: ScienceDaily
 

'Shock and kill' strategy for curing HIV may endanger patients' brains

Combination drug treatments have become successful at long-term control of HIV infection, but the goal of totally wiping out the virus and curing patients has so far been stymied by HIV's ability to hide out in cells and become dormant for long periods of time. One of the proposed curative strategies for HIV, known as "shock and kill," may be harmful to patients' brains, warn researchers. 

Brain cells from an SIV-infected macaque treated with ingenol and vorinostat. Macrophages are marked in green and the virus in red; virus-infected macrophages appear orange/yellow (arrows). Blue marks the nuclei of all cells.

Credit: Stephen Wietgrefe

 

One of the proposed curative strategies for HIV, known as "shock and kill," first uses so-called latency-reversing agents to wake up dormant viruses in the body, making them vulnerable to the patient's immune system. The idea is that this, in combination with antiretroviral medicines, would wipe out the majority of infected cells.
But based on a study of macaques with SIV, a group of researchers warns in a report published in the January 2 issue of the journal AIDS that such a strategy could cause potentially harmful brain inflammation.
"The potential for the brain to harbor significant HIV reservoirs that could pose a danger if activated hasn't received much attention in the HIV eradication field," says Janice Clements, Ph.D., professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine. "Our study sounds a major cautionary note about the potential for unintended consequences of the shock-and-kill treatment strategy."
HIV research efforts have long focused on prevention and developing antiretroviral therapies that keep the virus in check without eradicating it, essentially transforming HIV into a manageable chronic condition, says Lucio Gama, Ph.D., assistant professor of molecular and comparative pathobiology at Johns Hopkins and the lead author of the new study. Then, in 2009, a group in Berlin reported it had cured a man of HIV by giving him a bone marrow transplant from a donor whose genetics conferred natural resistance to the virus. This galvanized federal funding of new research projects aimed at finding a more broadly applicable "AIDS cure," Gama says. He and Clements are part of that pursuit as members of the Collaboratory of AIDS Researchers for Eradication.
One cure strategy being pursued is to find a medication that would "wake up" virus in the reservoirs, forcing it to reveal itself. But Gama says that could be problematic if HIV reservoirs exist in the brain, and investigators already had some evidence that they do: the many cases of AIDS dementia that developed before the current antiretroviral cocktail treatment was developed. "Research had also shown that HIV can infect monocytes in the blood, which we know cross into the brain," he says. But no studies had definitively answered whether significant reservoirs of latent HIV in patients under long-term therapy could be sustained in the brain -- in part because, in autopsies, it is unclear whether virus detected in the brain comes from brain cells themselves or surrounding blood.
For the new study, Clements, Gama and their collaborators treated three pig-tailed macaque monkeys infected with SIV with antiretrovirals for more than a year. Then the researchers gave two of the macaques ingenol-B, a latency-reversing agents thought to "wake up" the virus. "We didn't really see any significant effect," Gama says, "So we coupled ingenol-B with another latency-reversing agent, vorinostat, which is used in some cancer treatments to make cancer cells more vulnerable to the immune system." The macaques also continued their course of antiretrovirals throughout the experiment.
After a 10-day course of the combined treatment, one of the macaques remained healthy, while the other developed symptoms of encephalitis, or brain inflammation, Gama says, and blood tests revealed an active SIV infection. When the animal's illness worsened, the researchers humanely killed it and carefully removed the blood from its body so that blood sources of the virus would not muddle their examination of the brain. Testing revealed SIV was still present in the brain, but only in one of the regions analyzed: the occipital cortex, which processes visual information. The affected area was so small that "we almost missed it," he says.
Gama cautions that the results of their study on macaques with SIV may not apply to humans with HIV. It's also possible, he says, that the encephalitis was transient and could have resolved by itself. Still, he says, the results signal a need for extra caution in exploring ways to flush out HIV reservoirs and eradicate the virus from the body.
 

ournal Reference:

1. Lucio Gama, Celina M. Abreu, Erin N. Shirk, Sarah L. Price, Ming Li, Greg M. Laird, Kelly A. Metcalf Pate, Stephen W. Wietgrefe, Shelby L. O’Connor, Luiz Pianowski, Ashley T. Haase, Carine Van Lint, Robert F. Siliciano, Janice E. Clements. Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques. AIDS, 2017; 31 (1): 5 DOI: 10.1097/QAD.0000000000001267 

Courtesy: ScienceDaily
 

Gut microbes promote motor deficits in a mouse model of Parkinson's disease

Gut microbes may play a critical role in the development of Parkinson's-like movement disorders in genetically predisposed mice, researchers report. Antibiotic treatment reduced motor deficits and molecular hallmarks of Parkinson's disease in a mouse model, whereas transplantation of gut microbes from patients with Parkinson's disease exacerbated symptoms in these mice. The findings could lead to new treatment strategies for the second most common neurodegenerative disease in the United States. 

This research depicts the findings of Sampson et al., who show that signals from gut microbes are required for the neuroinflammatory responses as well as hallmark gastrointestinal and a-synuclein-dependent motor deficits in a model of Parkinson's disease.

Credit: Sampson et al./Cell 2016

 

"We have discovered for the first time a biological link between the gut microbiome and Parkinson's disease. More generally, this research reveals that a neurodegenerative disease may have its origins in the gut, and not only in the brain as had been previously thought," says senior study author Sarkis Mazmanian of the California Institute of Technology. "The discovery that changes in the microbiome may be involved in Parkinson's disease is a paradigm shift and opens entirely new possibilities for treating patients."
Parkinson's disease affects an estimated one million people and 1% of the United States population over 60 years of age. The disease is caused by the accumulation of abnormally shaped α-synuclein proteins in neurons, leading to particularly toxic effects in dopamine-releasing cells located in brain regions that control movement. As a result, patients experience debilitating symptoms such as tremors, muscle stiffness, slowness of movement, and impaired gait. First-line therapies currently focus on increasing dopamine levels in the brain, but these treatments can cause serious side effects and often lose effectiveness over time.
To address the need for safer and more effective treatments, Mazmanian and first author Timothy Sampson of the California Institute of Technology turned to gut microbes as an intriguing possibility. Patients with Parkinson's disease have an altered gut microbiome, and gastrointestinal problems such as constipation often precede motor deficits by many years in these individuals. Moreover, gut microbes have been shown to influence neuronal development, cognitive abilities, anxiety, depression, and autism. However, experimental evidence supporting a role for gut microbes in neurodegenerative diseases has been lacking.
The researchers raised genetically modified mice with a Parkinson's-like disease either in normal, non-sterile cages or in a germ-free environment. Remarkably, mice raised in the germ-free cages displayed fewer motor deficits and reducedaccumulation of misfolded protein aggregates in brain regions involved in controlling movement. In fact, these mice showed almost normal performance on tasks such as traversing a beam, removing an adhesive from their nose, and climbing down a pole.
Antibiotic treatment had a similar effect as the germ-free environment on ameliorating motor symptoms in mice predisposed to Parkinson's-like disorders. By contrast, mice raised in the germ-free cages showed worse motor symptoms when they either were treated with microbial metabolites called short-chain fatty acids or received fecal transplants of gut microbes from patients with Parkinson's disease. Taken together, the results suggest that gut microbes exacerbate motor symptoms by creating an environment that could favor the accumulation of misfolded protein aggregates.
It is important to note that, in this study, gut microbes cooperate with a specific genetic factor to influence the risk for developing Parkinson's disease. The researchers used a specific genetic mouse model that recapitulates motor symptoms through α-synuclein accumulation, and genetically normal mice that were not predisposed to Parkinson's disease did not develop motor symptoms after receiving fecal transplants from patients. Other genetic and environmental factors, such as pesticide exposure, also play a role in the disease.
The findings suggest that probiotic or prebiotic therapies have the potential to alleviate the symptoms of Parkinson's disease. However, antibiotics or fecal microbe transplants are far from being viable therapies at this time. "Long-term, high-strength antibiotic use, like we utilized in this study, comes with significant risk to humans, such as defects in immune and metabolic function," Sampson cautions. "Gut bacteria provide immense physiological benefit, and we do not yet have the data to know which particular species are problematic or beneficial in Parkinson's disease."
It is therefore critical to identify which pathogenic microbes might contribute to a higher Parkinson's disease risk or to development of a more severe symptomatology -- a research direction the researchers are planning to take. They will also look for specific bacterial species that may protect patients against motor decline. In the end, the identification of microbial species or metabolites that are altered in Parkinson's disease may serve as disease biomarkers or even drug targets, and interventions that correct microbial imbalances may provide safe and effective treatments to slow or halt the progression of often debilitating motor symptoms.
"Much like any other drug discovery process, translating this innovative work from mice to humans will take many years," Mazmanian says. "But this is an important first step toward our long-term goal of leveraging the deep, mechanistic insights that we have uncovered for a gut-brain connection to help ease the medical, economic, and social burden of Parkinson's disease."
 

Journal Reference:

1. Timothy R. Sampson et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell, December 2016 DOI: 10.1016/j.cell.2016.11.018 

Courtesy: ScienceDaily
 

 

Platypus venom could hold key to diabetes treatment

Australian researchers have discovered remarkable evolutionary changes to insulin regulation in two of the nation's most iconic native animal species -- the platypus and the echidna -- which could pave the way for new treatments for type 2 diabetes in humans. The findings reveal that the same hormone produced in the gut of the platypus to regulate blood glucose is also surprisingly produced in their venom. 

The findings, now published in the Nature journal Scientific Reports, reveal that the same hormone produced in the gut of the platypus to regulate blood glucose is also surprisingly produced in their venom.
The research is led by Professor Frank Grutzner at the University of Adelaide and Associate Professor Briony Forbes at Flinders University.
The hormone, known as glucagon-like peptide-1 (GLP-1), is normally secreted in the gut of both humans and animals, stimulating the release of insulin to lower blood glucose.
But GLP-1 typically degrades within minutes.
In people with type 2 diabetes, the short stimulus triggered by GLP-1 isn't sufficient to maintain a proper blood sugar balance. As a result, medication that includes a longer lasting form of the hormone is needed to help provide an extended release of insulin.
"Our research team has discovered that monotremes -- our iconic platypus and echidna -- have evolved changes in the hormone GLP-1 that make it resistant to the rapid degradation normally seen in humans," says co-lead author Professor Frank Grutzner, from the University of Adelaide's School of Biological Sciences and the Robinson Research Institute.
"We've found that GLP-1 is degraded in monotremes by a completely different mechanism. Further analysis of the genetics of monotremes reveals that there seems to be a kind of molecular warfare going on between the function of GLP-1, which is produced in the gut but surprisingly also in their venom," he says.
The platypus produces a powerful venom during breeding season, which is used in competition among males for females.
"We've discovered conflicting functions of GLP-1 in the platypus: in the gut as a regulator of blood glucose, and in venom to fend off other platypus males during breeding season. This tug of war between the different functions has resulted in dramatic changes in the GLP-1 system," says co-lead author Associate Professor Briony Forbes, from Flinders University's School of Medicine.
"The function in venom has most likely triggered the evolution of a stable form of GLP-1 in monotremes. Excitingly, stable GLP-1 molecules are highly desirable as potential type 2 diabetes treatments," she says.
Professor Grutzner says: "This is an amazing example of how millions of years of evolution can shape molecules and optimise their function.
"These findings have the potential to inform diabetes treatment, one of our greatest health challenges, although exactly how we can convert this finding into a treatment will need to be the subject of future research."
GLP-1 has also been discovered in the venom of echidnas. But while the platypus has spurs on its hind limbs for delivering a large amount of venom to its opponent, there is no such spur on echidnas.
"The lack of a spur on echidnas remains an evolutionary mystery, but the fact that both platypus and echidnas have evolved the same long-lasting form of the hormone GLP-1 is in itself a very exciting finding," Professor Grutzner says.
 

 

ournal Reference:

1. Enkhjargal Tsend-Ayush, Chuan He, Mark A. Myers, Sof Andrikopoulos, Nicole Wong, Patrick M. Sexton, Denise Wootten, Briony E. Forbes, Frank Grutzner. Monotreme glucagon-like peptide-1 in venom and gut: one gene – two very different functions. Scientific Reports, 2016; 6: 37744 DOI: 10.1038/srep37744 

Courtesy: ScienceDaily
 

 

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