Scientists grow an organ in an animal from cells created in lab

Laboratory-grown replacement organs have moved a step closer with the completion of a new study. Scientists have grown a fully functional organ from transplanted laboratory-created cells in a living animal for the first time.

Scientists have grown a fully functional organ from transplanted laboratory-created cells in a living animal for the first time. They grew a working thymus -- an important organ that supplies the body with immune cells. Left: Specialised thymus cells were created in the lab from a completely different cell type using a technique called reprogramming. Right: The laboratory-created cells were transplanted onto a mouse kidney to form an organised and functional mini-thymus in a living animal.

 

The researchers have created a thymus -- an organ next to the heart that produces immune cells known as T cells that are vital for guarding against disease.

They hope that, with further research, the discovery could lead to new treatments for people with a weakened immune system.

The team from the MRC Centre for Regenerative Medicine at the University of Edinburgh took cells called fibroblasts from a mouse embryo. They turned the fibroblasts into a completely different type of cell called thymus cells, using a technique called reprogramming.

The reprogrammed cells changed shape to look like thymus cells and were also capable of supporting development of T cells in the lab -- a specialised function that only thymus cells can perform.

When the researchers mixed reprogrammed cells with other key thymus cell types and transplanted them into a mouse, the cells formed a replacement organ. The new organ had the same structure, complexity and function as a healthy adult thymus.

It is the first time that scientists have made an entire living organ from cells that were created outside of the body by reprogramming.

Doctors have already shown that patients with thymus disorders can be treated with infusions of extra immune cells or transplantation of a thymus organ soon after birth. The problem is that both are limited by a lack of donors and problems matching tissue to the recipient.

With further refinement, the researchers hope that their lab-grown cells could form the basis of a thymus transplant treatment for people with a weakened immune system.

The technique may also offer a way of making patient-matched T cells in the laboratory that could be used in cell therapies.

Such treatments could benefit bone marrow transplant patients, by helping speed up the rate at which they rebuild their immune system after transplant.

The discovery offers hope to babies born with genetic conditions that prevent the thymus from developing properly. Older people could also be helped as the thymus is the first organ to deteriorate with age.

The study is published today in the journal Nature Cell Biology.

Professor Clare Blackburn from the MRC Centre for Regenerative Medicine at the University of Edinburgh, who led the research, said: "Our research represents an important step towards the goal of generating a clinically useful artificial thymus in the lab."

Dr Rob Buckle, Head of Regenerative Medicine at the MRC, said: "This is an exciting study but much more work will be needed before this process can be reproduced in a safe and tightly controlled way suitable for use in humans."

Journal Reference:

1. Nicholas Bredenkamp, Svetlana Ulyanchenko, Kathy Emma O’Neill, Nancy Ruth Manley, Harsh Jayesh Vaidya, Catherine Clare Blackburn. An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts. Nature Cell Biology, 2014; DOI: 10.1038/ncb3023 

Courtesy:ScienceDaily

Water splitter runs on an ordinary AAA battery

Hongjie Dai and colleagues have developed a cheap, emissions-free device that uses a 1.5-volt battery to split water into hydrogen and oxygen. The hydrogen gas could be used to power fuel cells in zero-emissions vehicles.

Stanford scientists have developed a low-cost device that uses an ordinary AAA battery to split water into oxygen and hydrogen gas. Gas bubbles are produced from electrodes made of inexpensive nickel and iron.

Stanford University Professor Hongjie Dai has developed an emissions-free electrolytic device that splits water into hydrogen and oxygen at room temperature.

In 2015, American consumers will finally be able to purchase fuel cell cars from Toyota and other manufacturers. Although touted as zero-emissions vehicles, most of the cars will run on hydrogen made from natural gas, a fossil fuel that contributes to global warming.

Now scientists at Stanford University have developed a low-cost, emissions-free device that uses an ordinary AAA battery to produce hydrogen by water electrolysis. The battery sends an electric current through two electrodes that split liquid water into hydrogen and oxygen gas. Unlike other water splitters that use precious-metal catalysts, the electrodes in the Stanford device are made of inexpensive and abundant nickel and iron.

"Using nickel and iron, which are cheap materials, we were able to make the electrocatalysts active enough to split water at room temperature with a single 1.5-volt battery," said Hongjie Dai, a professor of chemistry at Stanford. "This is the first time anyone has used non-precious metal catalysts to split water at a voltage that low. It's quite remarkable, because normally you need expensive metals, like platinum or iridium, to achieve that voltage."

In addition to producing hydrogen, the novel water splitter could be used to make chlorine gas and sodium hydroxide, an important industrial chemical, according to Dai. He and his colleagues describe the new device in a study published in the Aug. 22 issue of the journal Nature Communications.

The promise of hydrogen

Automakers have long considered the hydrogen fuel cell a promising alternative to the gasoline engine. Fuel cell technology is essentially water splitting in reverse. A fuel cell combines stored hydrogen gas with oxygen from the air to produce electricity, which powers the car. The only byproduct is water -- unlike gasoline combustion, which emits carbon dioxide, a greenhouse gas.

Stanford scientists have developed a low-cost device that uses an ordinary AAA battery to split water into oxygen and hydrogen gas. Gas bubbles are produced by electrodes made of inexpensive nickel and iron.

Earlier this year, Hyundai began leasing fuel cell vehicles in Southern California. Toyota and Honda will begin selling fuel cell cars in 2015. Most of these vehicles will run on fuel manufactured at large industrial plants that produce hydrogen by combining very hot steam and natural gas, an energy-intensive process that releases carbon dioxide as a byproduct.

Splitting water to make hydrogen requires no fossil fuels and emits no greenhouse gases. But scientists have yet to develop an affordable, active water splitter with catalysts capable of working at industrial scales.

"It's been a constant pursuit for decades to make low-cost electrocatalysts with high activity and long durability," Dai said. "When we found out that a nickel-based catalyst is as effective as platinum, it came as a complete surprise."

Saving energy and money

The discovery was made by Stanford graduate student Ming Gong, co-lead author of the study. "Ming discovered a nickel-metal/nickel-oxide structure that turns out to be more active than pure nickel metal or pure nickel oxide alone," Dai said. "This novel structure favors hydrogen electrocatalysis, but we still don't fully understand the science behind it."

The nickel/nickel-oxide catalyst significantly lowers the voltage required to split water, which could eventually save hydrogen producers billions of dollars in electricity costs, according to Gong. His next goal is to improve the durability of the device.

"The electrodes are fairly stable, but they do slowly decay over time," he said. "The current device would probably run for days, but weeks or months would be preferable. That goal is achievable based on my most recent results"

The researchers also plan to develop a water splitter than runs on electricity produced by solar energy.

"Hydrogen is an ideal fuel for powering vehicles, buildings and storing

renewable energy

on the grid," said Dai. "We're very glad that we were able to make a catalyst that's very active and low cost. This shows that through nanoscale engineering of materials we can really make a difference in how we make fuels and consume energy."

Other authors of the study are Wu Zhou, Oak Ridge National Laboratory (co-lead author); Mingyun Guan, Meng-Chang Lin, Bo Zhang, Di-Yan Wang and Jiang Yang, Stanford; Mon-Che Tsai and Bing-Joe Wang, National Taiwan University of Science and Technology; Jiang Zhou and Yongfeng Hu, Canadian Light Source Inc.; and Stephen J. Pennycook, University of Tennessee.

Journal Reference:

1. Ming Gong, Wu Zhou, Mon-Che Tsai, Jigang Zhou, Mingyun Guan, Meng-Chang Lin, Bo Zhang, Yongfeng Hu, Di-Yan Wang, Jiang Yang, Stephen J. Pennycook, Bing-Joe Hwang, Hongjie Dai. Nanoscale nickel oxide/nickel heterostructures for active hydrogen evolution electrocatalysis. Nature Communications, 2014; 5: 4695 DOI: 10.1038/ncomms5695

Courtesy: ScienceDaily

Creating pomegranate drug to stem Alzheimer's, Parkinson's

Dr. Olumayokun Olajide's research will look to produce compound derivatives of punicalagin for a drug that would treat neuro-inflammation and slow down the progression of Alzheimer's disease

The onset of Alzheimer's disease can be slowed and some of its symptoms curbed by a natural compound that is found in pomegranate. Also, the painful inflammation that accompanies illnesses such as rheumatoid arthritis and Parkinson's disease could be reduced, according to the findings of a two-year project headed by University of Huddersfield scientist Dr Olumayokun Olajide, who specialises in the anti-inflammatory properties of natural products.
Now, a new phase of research can explore the development of drugs that will stem the development of dementias such as Alzheimer's, which affects some 800,000 people in the UK, with 163,000 new cases a year being diagnosed. Globally, there are at least 44.4 million dementia sufferers, with the numbers expected to soar.
The key breakthrough by Dr Olajide and his co-researchers is to demonstrate that punicalagin, which is a polyphenol -- a form of chemical compound -- found in pomegranate fruit, can inhibit inflammation in specialised brain cells known as micrologia. This inflammation leads to the destruction of more and more brain cells, making the condition of Alzheimer's sufferers progressively worse.
There is still no cure for the disease, but the punicalagin in pomegranate could prevent it or slow down its development.
Dr Olajide worked with co-researchers -- including four PhD students -- in the University of Huddersfield's Department of Pharmacy and with scientists at the University of Freiburg in Germany. The team used brain cells isolated from rats in order to test their findings. Now the research is published in the latest edition of the journal Molecular Nutrition & Food Research and Dr Olajide will start to disseminate his findings at academic conferences.
He is still working on the amounts of pomegranate that are required, in order to be effective.
"But we do know that regular intake and regular consumption of pomegranate has a lot of health benefits -- including prevention of neuro-inflammation related to dementia," he says, recommending juice products that are 100 per cent pomegranate, meaning that approximately 3.4 per cent will be punicalagin, the compound that slows down the progression of dementia.
Dr Olajide states that most of the anti-oxidant compounds are found in the outer skin of the pomegranate, not in the soft part of the fruit. And he adds that although this has yet to be scientifically evaluated, pomegranate will be useful in any condition for which inflammation -- not just neuro-inflammation -- is a factor, such as rheumatoid arthritis, Parkinson's and cancer.
The research continues and now Dr Olajide is collaborating with his University of Huddersfield colleague, the organic chemist Dr Karl Hemming. They will attempt to produce compound derivatives of punicalagin that could the basis of new, orally administered drugs that would treat neuro-inflammation.
Dr Olajide has been a Senior Lecturer at the University of Huddersfield for four years. His academic career includes a post as a Humboldt Postdoctoral Research Fellow at the Centre for Drug Research at the University of Munich. His PhD was awarded from the University of Ibadan in his native Nigeria, after an investigation of the anti-inflammatory properties of natural products.
He attributes this area of research to his upbringing. "African mothers normally treat sick children with natural substances such as herbs. My mum certainly used a lot of those substances. And then I went on to study pharmacology!"
 

Journal Reference:

1. Olumayokun A. Olajide, Asit Kumar, Ravikanth Velagapudi, Uchechukwu P. Okorji, Bernd L. Fiebich. Punicalagin inhibits neuroinflammation in LPS-activated rat primary microglia. Molecular Nutrition & Food Research, 2014; DOI: 10.1002/mnfr.201400163 

Courtesy: ScienceDaily
 

Blood pressure medication does not cause more falls, study shows

It's time to question the common belief that patients receiving intensive blood pressure treatment are prone to falling and breaking bones. A comprehensive study in people ages 40 to 79 with diabetes, led by Karen Margolis, MD, of HealthPartners Institute for Education and Research in the US, found no evidence supporting this belief. The study appears in the Journal of General Internal Medicine, published by Springer.

Evidence from various clinical trials shows that cardiovascular events such as strokes can be prevented by treating high blood pressure (hypertension).. However, physicians and patients still often express concern that its tight control may increase a person's risk of low blood pressure (hypotension) and subsequent falls and fractures. Scientific data to support this notion are sparse. Therefore, Margolis and her associates compared the number of falls and fractures of type 2 diabetes patients receiving two types of blood pressure treatment. The intensive group (which included 1,534 participants) received treatment aimed at a systolic blood pressure of <120 for="" group="" hg.="" hg="" mm="" p="" participants="" standard="" target="" the="" was="" while="">

Participants were all part of ACCORD-BONE, an ancillary study of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial, which tested how more intensive treatment of blood sugar, blood pressure and lipids affected cardiovascular disease outcomes in people with diabetes. Participants in the ACCORD-BONE study were, on average, about 62 years old; none were 80 or older. The results show that patients who received intensive blood pressure treatment did not fall more than less intensively treated patients, nor did they incur more fractures over an average follow-up of about five years.

"Lowering blood pressure using intensive treatment compared with standard treatment did not result in an increased rate of falls or fractures and, in fact, showed possible trends towards fewer fractures in the intensively treated patients," explains Margolis. "Although intensive blood pressure treatment to the low levels in ACCORD did not lower cardiovascular events, our results and review of the literature suggest a need to carefully reconsider current thinking about whether antihypertensive treatment and blood pressure lowering increases risk for falls and fractures."

Results in older versus younger patients were not different. No evidence suggested that the risk of patients' falling varied over time, although there were not enough fractures to determine if the short-term risk might be higher at the beginning of intensive treatment. It is important to note that subjects in this study were more closely monitored than most patients in clinical practice; therefore, the results may not completely reflect what would happen in actual practice.

Journal Reference:

1. Karen L. Margolis, Lisa Palermo, Eric Vittinghoff, Gregory W. Evans, Hal H. Atkinson, Bruce P. Hamilton, Robert G. Josse, Patrick J. O’Connor, Debra L. Simmons, Margaret Tiktin, Ann V. Schwartz. Intensive Blood Pressure Control, Falls, and Fractures in Patients with Type 2 Diabetes: The ACCORD Trial. Journal of General Internal Medicine, 2014; DOI: 10.1007/s11606-014-2961-3

Courtesy: ScienceDaily

Hospital superbug breakthrough: Antibacterial gel kills Pseudomonas aeruginosa, staphylococci and E.coli using natural proteins

Scientists at Queen's University Belfast have made a breakthrough in the fight against the most resistant hospital superbugs.

 Catheter in arm (stock image). When bacteria attach to surfaces, including medical implants, they produce a jelly-like substance called the biofilm -- a protective layer is almost impossible for current antibiotics to penetrate through.

The team from the School of Pharmacy at Queen's have developed the first innovative antibacterial gel that acts to kill Pseudomonas aeruginosa, staphylococci and E.coli using natural proteins.

The gels have the ability to break down the thick jelly-like coating, known as biofilms, which cover bacteria making them highly resistant to current therapies, while leaving healthy cells unaffected.

Dr Garry Laverty, from the School of Pharmacy at Queen's University, and lead researcher, said: "When bacteria attach to surfaces, including medical implants such as hip replacements and catheters, they produce a jelly-like substance called the biofilm. This protective layer is almost impossible for current antibiotics to penetrate through. Therefore bacteria deep within this protective layer are resistant as they remain unexposed to the therapy. They grow and thrive on surfaces to cause infections that are very difficult to treat. The only option is often to remove the medical implant leading to further pain and discomfort for the patient. Our gels would prevent this.

"Our gels are unique as they target and kill the most resistant forms of hospital superbugs. It involves the use of gels composed of the building blocks of natural proteins, called peptides. The same ingredients that form human tissue. These molecules are modified slightly in the laboratory to allow them to form gels that will rapidly kill bacteria. This is further evidence of Queen's research advancing knowledge and changing lives."

The new approach, which was developed as part of an international collaboration between the School of Pharmacy at Queen's and the School of Chemistry at Brandeis University, Waltham, USA, is published in the journal Biomacromolecules next month.

The results will form part of a presentation delivered by Dr Laverty at the Academy of Pharmaceutical Sciences, UK PharmSci: The Science of Medicines conference at the University of Hertfordshire on the 8^th September 2014.

Journal Reference:

1. Garry Laverty, Alice P. McCloskey, Brendan F. Gilmore, David S. Jones, Jie Zhou, Bing Xu. Ultrashort Cationic Naphthalene-Derived Self-Assembled Peptides as Antimicrobial Nanomaterials. Biomacromolecules, 2014; 140807094711008 DOI: 10.1021/bm500981y

Courtesy: ScienceDaily

More than just X and Y: New genetic basis for sex determination

Men and women differ in plenty of obvious ways, and scientists have long known that genetic differences buried deep within our DNA underlie these distinctions. In the past, most research has focused on understanding how the genes that encode proteins act as sex determinants. But Cold Spring Harbor Laboratory (CSHL) scientists have found that a subset of very small genes encoding short RNA molecules, called microRNAs (miRNAs), also play a key role in differentiating male and female tissues in the fruit fly. 

Cold Spring Harbor Laboratory researchers have found that miRNAs, short RNA molecules, are responsible for sexual differences in fruit flies. Shown here are testes from a male fruit fly where a hormone that controls a key miRNA has been inactivated. The abnormal testes fail to make sperm. They now produce sex determinants (shown in red) that are found in the ovaries of female flies.

A miRNA is a short segment of RNA that fine-tunes the activation of one or several protein-coding genes. miRNAs are able to silence the genes they target and, in doing so, orchestrate complex genetic programs that are the basis of development.

In work published in Genetics, a team of CSHL researchers and colleagues describe how miRNAs contribute to sexual differences in fruit flies. You've probably never noticed, but male and female flies differ visibly, just like other animals. For example, females are 25% larger than males with lighter pigmentation and more abdominal segments.

The team of researchers, including Delphine Fagegaltier, PhD, lead author on the study, and CSHL Professor and Howard Hughes Medical Institute Investigator Greg Hannon, identified distinct miRNA populations in male and female flies. "We found that the differences in miRNAs are important in shaping the structures that distinguish the two sexes," says Fagegaltier. "In fact, miRNAs regulate the very proteins that act as sex determinants during development."

The team found that miRNAs are essential for sex determination even after an animal has grown to adulthood. "They send signals that allow germ cells, i.e., eggs and sperm, to develop, ensuring fertility," Fagegaltier explains. "Removing one miRNA from mature, adult flies causes infertility." More than that, these flies begin to produce both male and female sex-determinants. "In a sense, once they have lost this miRNA, the flies become male and female at the same time," according to Fagegaltier. "It is amazing that the very smallest genes can have such a big effect on sexual identity."

Some miRNAs examined in the study, such as let-7, have been preserved by evolution because of their utility; humans and many other animals carry versions of them. "This is probably just the tip of the iceberg," says Fagegaltier. "There are likely many more miRNAs regulating sexual identity at the cellular and tissue level, but we still have a lot to learn about these differences in humans, and how they could contribute to developmental defects and disease."

Journal Reference:

1. D. Fagegaltier, A. Konig, A. Gordon, E. C. Lai, T. R. Gingeras, G. J. Hannon, H. R. Shcherbata. A Genome-Wide Survey of Sexually Dimorphic Expression of Drosophila miRNAs Identifies the Steroid Hormone-Induced miRNA let-7 as a Regulator of Sexual Identity. Genetics, 2014; DOI: 10.1534/genetics.114.169268 

Courtesy: ScienceDaily

Talking 'bout regeneration: How do some animals regrow missing parts?

Regeneration is one of the most tantalizing areas of biological research. How are some animals able to regrow body parts following injury? Why can't humans do the same thing? Can scientists learn the secrets that imbue certain animals with this amazing ability? Could that knowledge someday be used to develop new therapies to help people heal?

The axolotl, a rare type of salamander found wild only in a small area in Mexico, is a master of 

regeneration, able to regrow just about any part of its body, including brain structures.

Four professors in the University of Kentucky Department of Biology -- Randal Voss, Jeramiah Smith, Ann Morris, and Ashley Seifert -- are undertaking the basic scientific research needed to begin to answer these and other questions. Each of them approaches the problem from a different angle, focusing on different aspects of regeneration, and using different vertebrate models.

This formula, of divergent research programs with a common, uniting focus, has fostered a dynamic and productive collaboration among this group. Together, these four make up the core of an unofficial regeneration "cluster" within the department.

At its base, vertebrate regeneration requires a complex molecular crosstalk between cells, similar in many ways to the cellular "communication" that occurs in the development of an animal from a single cell to an adult organism. Certain genes are activated or deactivated at specific times to turn undifferentiated cells into tissues and organs, and to arrange them into complicated body parts such as limbs and joints.

We humans carry in our DNA a genetic legacy that we share with all other vertebrates, a common set of genes that successive generations have carried forward for hundreds of millions of years. By studying the genetic mechanisms that enable regeneration in our distant evolutionary cousins, scientists hope to one day uncover potentially latent healing abilities that may lie hidden in our own genome.

Jeramiah Smith is a genomics expert who works with sea lampreys. These jawless, eel-like creatures diverged from our common ancestors in the Cambrian Period, about 500 million years ago. Lampreys have the ability to regenerate spinal cord cells, which is a neat trick for any vertebrate. But Smith says a big part of the appeal for him in studying these animals lies in excavating the natural history cached in their DNA.

"If I had my choice of a career and didn't have to think about paying for my kids' school and all that stuff, I would probably be a paleontologist and dig for fossils," he says. "But really, genomics is almost as pleasing, if not more pleasing than that. By accessing the genomes of these animals, describing them, and then comparing them with other genomes that have been sequenced, you're often the first person to know what was going on half a billion years ago. It's sort of like the kid-in-the-dinosaur-museum thing."

Smith also works closely with Stephen Randal Voss, sequencing the genome of salamanders, an amphibian group that veered off our common vertebrate path about 300 million years ago. Though we share many of the same genes, the salamander genome is massive compared to our own -- about 10 times as large.

Voss's research focuses on axolotls, an unusual type of salamander that lives wild only in one tiny part of Mexico. Unlike most salamanders, which undergo a metamorphosis from larva to adult, axolotls retain their juvenile form throughout their entire lifespan, a trait known as neotony or paedomorphism. But the main reason that axolotls are among the most-studied salamanders in the world is their amazing ability to regenerate a variety of body parts.

"It's hard to find a body part they can't regenerate," Voss says. "Salamanders in general, and axolotls especially so. The limbs, the tail, the spinal cord -- even half of their brain has been removed and shown to regenerate."

Voss's research involves assembling a vast store of genetic data using RNA extracted from regenerated axolotl tissue. From this data, Voss will elaborate a model for how genes are turned on and off over very small timescales. This model will serve as a blueprint for other regeneration researchers to build from.

Sandwiched between the sea lamprey and the axolotl on evolution's vast timeline -- about 400 million years ago -- another vertebrate appeared on the scene with the ability to regenerate an impressive variety of different tissues: the zebrafish. This minnow-like freshwater fish is central to the research of Ann Morris, who is interested specifically in its ability to regenerate retinal cells.

We humans lack that ability. Degenerative diseases of the retina -- such as retinitis pigmentosa or macular degeneration -- are the leading causes of blindness in older adults. If scientists can learn how zebrafish are able to repair their retinas, it could point the way to new strategies for developing treatments to preserve vision, or perhaps even to restore it, in humans.

The structure of the retina and the types of cells found therein are similar across all vertebrates. By studying how the retina develops in zebrafish embryos, Morris says, researchers can learn a great deal about how the process works in mammals, and specifically in humans.

An oft-repeated maxim in biology classrooms is that "regeneration recapitulates development." So, if our retinas are so similar in their development, how is it that zebrafish can regenerate retinal cells and we can't? That's an excellent question, Morris says. The answer is suspended between between two distinct possibilities.

"One is that at some point, everybody had the ability to regenerate, and that ability in certain lineages was eventually lost," Morris said. "So, perhaps all the mechanism is still there in the genome, and it just needs to be reactivated. The other is that as these different vertebrate lineages diverged, certain vertebrates evolved that ability whereas others didn't. I happen to believe it's probably more of the former, that some of those abilities are there and they're latent, and we have to discover how to reactivate them."

One possibility is that mammals essentially "traded" much of their regeneration ability in evolving adaptive immune systems. Animals that

excel

at regeneration tend not to exhibit the same responses to injury that mammals do -- such as inflammation and scar formation -- and mammals generally lag far behind other vertebrates in their ability to regrow missing parts.

That's what makes the African spiny mouse, a sort of master of regeneration in mammalian circles, so remarkable. Ashley Seifert, whose research is focused on skin regeneration, started studying these animals about five years ago, shifting from a salamander model.

"What's phenomenal is that they're able to regenerate complex tissue structures," Seifert said. "They can regenerate all of the components of their skin including hair follicles, sebaceous glands and the underlying dermis, the structural component which gives the skin strength. And then, in the ears, amazingly, they can regenerate cartilage. Any orthopedic surgeon will tell you what a huge advance it would be if we could figure out how to regenerate cartilage in a mammal."

Seifert's research has taken him and postdoctoral scholar Tom Gawriluk to Kenya for the summer, where they will divide their time between trapping spiny mice in the wild and working with colleagues at the University of Nairobi and the University of Georgia to examine how immune tradeoffs can affect regenerative ability.

In spite of their disparate approaches, all four researchers agree that the regeneration cluster that has cohered in the Department of Biology has potential for growth. In fact, Voss says, the group's diversity is perhaps its greatest strength.

"I think it's fantastic that we have researchers in the department that each have a model representing one of the major vertebrate classes," Voss said. "We're only missing somebody to work on reptiles at this point. It's not beyond the realm of possibility to think about creating a center. We're all taking a very systematic, systems biology approach to the problem. If we had a 'Biocomplexity in Systems Biology' theme that brought us together, with regeneration being the problem that brought us together under that umbrella, that would be a great next step."

A video featuring the regeneration cluster scientists talking about their work may be viewed online at https://www.youtube.com/watch?v=K39qgZEKSwc.

Story Source:
The above story is based on materials provided by University of Kentucky. The original article was written by Keith Hautala. Note: Materials may be edited for content and length.

Courtesy: Science Daily

Link between vitamin D, dementia risk confirmed

Vitamin D deficiency is associated with a substantially increased risk of dementia and Alzheimer's disease in older people, according to the most robust study of its kind ever conducted.

An international team, led by Dr David Llewellyn at the University of Exeter Medical School, found that study participants who were severely Vitamin D deficient were more than twice as likely to develop dementia and Alzheimer's disease.

The team studied elderly Americans who took part in the Cardiovascular Health Study. They discovered that adults in the study who were moderately deficient in vitamin D had a 53 per cent increased risk of developing dementia of any kind, and the risk increased to 125 per cent in those who were severely deficient.

Similar results were recorded for Alzheimer's disease, with the moderately deficient group 69 per cent more likely to develop this type of dementia, jumping to a 122 per cent increased risk for those severely deficient.

The study was part-funded by the Alzheimer's Association, and is published in Neurology, the medical journal of the American Academy of Neurology. It looked at 1,658 adults aged 65 and over, who were able to walk unaided and were free from dementia, cardiovascular disease and stroke at the start of the study. The participants were then followed for six years to investigate who went on to develop Alzheimer's disease and other forms of dementia.

Dr Llewellyn said: "We expected to find an association between low Vitamin D levels and the risk of dementia and Alzheimer's disease, but the results were surprising -- we actually found that the association was twice as strong as we anticipated.

"Clinical trials are now needed to establish whether eating foods such as oily fish or taking vitamin D supplements can delay or even prevent the onset of Alzheimer's disease and dementia. We need to be cautious at this early stage and our latest results do not demonstrate that low vitamin D levels cause dementia. That said, our findings are very encouraging, and even if a small number of people could benefit, this would have enormous public health implications given the devastating and costly nature of dementia."

Research collaborators included experts from Angers University Hospital, Florida International University, Columbia University, the University of Washington, the University of Pittsburg and the University of Michigan. The study was supported by the Alzheimer's Association, the Mary Kinross Charitable Trust, the James Tudor Foundation, the Halpin Trust, the Age Related Diseases and Health Trust, the Norman Family Charitable Trust, and the National Institute for Health Research Collaboration for Leadership in Applied Research and Care South West Peninsula (NIHR PenCLAHRC).

Dementia is one of the greatest challenges of our time, with 44 million cases worldwide -- a number expected to triple by 2050 as a result of rapid population aging. A billion people worldwide are thought to have low vitamin D levels and many older adults may experience poorer health as a result.

The research is the first large study to investigate the relationship between vitamin D and dementia risk where the diagnosis was made by an expert multidisciplinary team, using a wide range of information including neuroimaging. Previous research established that people with low vitamin D levels are more likely to go on to experience cognitive problems, but this study confirms that this translates into a substantial increase in the risk of Alzheimer's disease and dementia.

Vitamin D comes from three main sources -- exposure of skin to sunlight, foods such as oily fish, and supplements. Older people's skin can be less efficient at converting sunlight into Vitamin D, making them more likely to be deficient and reliant on other sources. In many countries the amount of UVB radiation in winter is too low to allow vitamin D production.

The study also found evidence that there is a threshold level of Vitamin D circulating in the bloodstream below which the risk of developing dementia and Alzheimer's disease increases. The team had previously hypothesized that this might lie in the region of 25-50 nmol/L, and their new findings confirm that vitamin D levels above 50 nmol/L are most strongly associated with good brain health.

Commenting on the study, Dr Doug Brown, Director of Research and Development at Alzheimer's Society said: "Shedding light on risk factors for dementia is one of the most important tasks facing today's health researchers. While earlier studies have suggested that a lack of the sunshine vitamin is linked to an increased risk of Alzheimer's disease, this study found that people with very low vitamin D levels were more than twice as likely to develop any kind of dementia.

"During this hottest of summers, hitting the beach for just 15 minutes of sunshine is enough to boost your vitamin D levels. However, we're not quite ready to say that sunlight or vitamin D supplements will reduce your risk of dementia. Large scale clinical trials are needed to determine whether increasing vitamin D levels in those with deficiencies can help prevent the dementia from developing."

Journal Reference:

1. Thomas J. Littlejohns, William E. Henley, Iain A. Lang, Cedric Annweiler, Olivier Beauchet, Paulo H.m. Chaves, Linda Fried, Bryan R. Kestenbaum, Lewis H. Kuller, Kenneth M. Langa, Oscar L. Lopez, Katarina Kos, Maya Soni, and David J. Llewellyn. Vitamin D and the risk of dementia and Alzheimer disease. Neurology, August 2014 DOI: 10.1212/WNL.0000000000000755 

Courtesy: ScienceDaily

Dramatic growth of grafted stem cells in rat spinal cord

Building upon previous research, scientists at the University of California, San Diego School of Medicine and Veteran's Affairs San Diego Healthcare System report that neurons derived from human induced pluripotent stem cells (iPSC) and grafted into rats after a spinal cord injury produced cells with tens of thousands of axons extending virtually the entire length of the animals' central nervous system.

This image depicts extension of human axons into host adult rat white matter and gray matter three months after spinal cord injury and transplantation of human induced pluripotent stem cell-derived neurons. Green fluorescent protein identifies human graft-derived axons, myelin (red) indicates host rat spinal cord white matter and blue marks host rat gray matter.

Writing in the August 7 early online edition of Neuron, lead scientist Paul Lu, PhD, of the UC San Diego Department of Neurosciences and colleagues said the human iPSC-derived axons extended through the white matter of the injury sites, frequently penetrating adjacent gray matter to form synapses with rat neurons. Similarly, rat motor axons pierced the human iPSC grafts to form their own synapses.

The iPSCs used were developed from a healthy 86-year-old human male.

"These findings indicate that intrinsic neuronal mechanisms readily overcome the barriers created by a spinal cord injury to extend many axons over very long distances, and that these capabilities persist even in neurons reprogrammed from very aged human cells," said senior author Mark Tuszynski, MD, PhD, professor of Neurosciences and director of the UC San Diego Center for Neural Repair.

For several years, Tuszynski and colleagues have been steadily chipping away at the notion that a spinal cord injury necessarily results in permanent dysfunction and paralysis. Earlier work has shown that grafted stem cells reprogrammed to become neurons can, in fact, form new, functional circuits across an injury site, with the treated animals experiencing some restored ability to move affected limbs. The new findings underscore the potential of iPSC-based therapy and suggest a host of new studies and questions to be asked, such as whether axons can be guided and how will they develop, function and mature over longer periods of time.

While neural stem cell therapies are already advancing to clinical trials, this research raises cautionary notes about moving to human therapy too quickly, said Tuszynski.

"The enormous outgrowth of axons to many regions of the spinal cord and even deeply into the brain raises questions of possible harmful side effects if axons are mistargeted. We also need to learn if the new connections formed by axons are stable over time, and if implanted human neural stem cells are maturing on a human time frame -- months to years -- or more rapidly. If maturity is reached on a human time frame, it could take months to years to observe functional benefits or problems in human clinical trials."

In the latest work, Lu, Tuszynski and colleagues converted skin cells from a healthy 86-year-old man into iPSCs, which possess the ability to become almost any kind of cell. The iPSCs were then reprogrammed to become neurons in collaboration with the laboratory of Larry Goldstein, PhD, director of the UC San Diego Sanford Stem Cell Clinical Center. The new human neurons were subsequently embedded in a matrix containing growth factors and grafted into two-week-old spinal cord injuries in rats.

Three months later, researchers examined the post-transplantation injury sites. They found biomarkers indicating the presence of mature neurons and extensive axonal growth across long distances in the rats' spinal cords, even extending into the brain. The axons traversed wound tissues to penetrate and connect with existing rat neurons. Similarly, rat neurons extended axons into the grafted material and cells. The transplants produced no detectable tumors.

While numerous connections were formed between the implanted human cells and rat cells, functional recovery was not found. However, Lu noted that tests assessed the rats' skilled use of the hand. Simpler assays of leg movement could still show benefit. Also, several iPSC grafts contained scars that may have blocked beneficial effects of new connections. Continuing research seeks to optimize transplantation methods to eliminate scar formation.

Tuszynski said he and his team are attempting to identify the most promising neural stem cell type for repairing spinal cord injuries. They are testing iPSCs, embryonic stem cell-derived cells and other stem cell types.

"Ninety-five percent of human clinical trials fail. We are trying to do as much as we possibly can to identify the best way of translating neural stem cell therapies for spinal cord injury to patients. It's easy to forge ahead with incomplete information, but the risk of doing so is greater likelihood of another failed clinical trial. We want to determine as best we can the optimal cell type and best method for human translation so that we can move ahead rationally and, with some luck, successfully."

Journal Reference:

1. Lu et al. Long-Distance Axonal Growth from Human Induced Pluripotent Stem Cells After Spinal Cord Injury. Neuron, 2014 (in press)

Courtesy: ScienceDaily

Newly discovered gut virus lives in half the world's population

Odds are, there's a virus living inside your gut that has gone undetected by scientists for decades. A new study led by researchers at San Diego State University has found that more than half the world's population is host to a newly described virus, named crAssphage, which infects one of the most common types of gut bacteria, Bacteroidetes. This phylum of bacteria is thought to be connected with obesity, diabetes and other gut-related diseases.

 

 Above: Robert Edwards, associate professor of computer science. The virus, named crAssphage, has about 10 times as many base pairs of DNA as HIV.

The research appears today in Nature Communications.
Robert A. Edwards, a bioinformatics professor at SDSU, and his colleagues stumbled upon the discovery quite by accident. Working with visiting researcher and corresponding author on the study Bas E. Dutilh, now at Radboud University Medical Center in The Netherlands, the researchers were using results from previous studies on gut-inhabiting viruses to screen for new viruses.
In the DNA fecal samples from 12 different individuals, they noticed a particular cluster of viral DNA, about 97,000 base pairs long, that the samples all had in common. When Edwards and his colleagues checked this discovery against a comprehensive listing of known viruses, they came up empty.
The researchers then screened for the virus across the database of the National Institute of Health's Human Microbiome Project (HMP), and Argonne National Laboratory's MG-RAST database, and again found it in abundance in samples derived from human feces.
To prove that the viral DNA they discovered in their computer data actually exists in nature, fellow SDSU virologist John Mokili used a technique known as DNA amplification to locate the virus in the original samples used to build NIH's database.
"So we have a biological proof that the virus they found with the computer actually exists in the samples," Mokili said.
This was a new virus that about half the sampled people had in their bodies that nobody knew about.
"It's not unusual to go looking for a novel virus and find one," Edwards said. "But it's very unusual to find one that so many people have in common. The fact that it's flown under the radar for so long is very strange."
An ancient virus
The fact that it's so widespread indicates that it probably isn't a particularly young virus, either.
"We've basically found it in every population we've looked at," Edwards said. "As far as we can tell, it's as old as humans are."
He and his team named the virus crAssphage, after the cross-assembly software program used to discover it.
Some of the proteins in crAssphage's DNA are similar to those found in other well-described viruses. That allowed Edwards' team to determine that their novel virus is one known as a bacteriophage, which infects and replicates inside bacteria -- and using innovative bioinformatic techniques, they predicted that this particular bacteriophage proliferates by infecting a common phylum of gut bacteria known as Bacteriodetes.
Gut punch
Bacteriodetes bacteria live toward the end of the intestinal tract, and they are suspected to play a major role in the link between gut bacteria and obesity. What role crAssphage plays in this process will be a target of future research.
Further details about crAssphage have been difficult to come by. It's unknown how the virus is transmitted, but the fact that it was not found in very young infants' fecal samples suggests that it is not passed along maternally, but acquired during childhood. The makeup of the viral DNA suggests that it's circular in structure. Further laboratory work has confirmed that the viral DNA is a singular entity, but it's proven difficult to isolate.
"We know it's there, but we can't capture it quite yet," Edwards said.
Once the virus is isolated, he hopes to delve into its role in obesity. It's possible the virus in some way mediates the activity of Bacteriodetes colonies, but whether crAssphage promotes or suppresses obesity-related processes in the gut remains to be seen.
The virus might also be used to prevent or mitigate other diseases affected by the gut such as diabetes and gastroenterological maladies.
Once these processes are better understood, Edwards envisions one day the possibility of personalized medicine based on this virus.
"This could be a key to personalized phage medicine," he said. "In individuals, we could isolate your particular strain of the virus, manipulate it to target harmful bacteria, then give it back to you."
Key Collaborators
In addition to Edwards, SDSU researchers Katelyn McNair, Savannah Sanchez, Genivaldo G.Z. Silva, Lance Boling, Jeremy J. Barr, Victor Seguritan, Ben Felts, and Elizabeth A. Dinsdale worked on the project, in collaboration with Argonne National Laboratory in Illinois. The study's corresponding author, Bas E. Dutilh, shares an affiliation with SDSU, Radboud University Medical Center in The Netherlands, and the Federal University of Rio de Janeiro in Brazil. Contributing researcher Ramy K. Aziz shares an affiliation with SDSU and Cairo University in Egypt. Contributing researcher Noriko Cassman was at SDSU during the time of the study and now is at the Netherlands Institute of Ecology.
San Diego State University is a leading institution for bacteriophage research. Its Viromics Information Institute, which has been identified as an SDSU Area of Excellence, is led by biology professors Forest Rohwer, Anca Segall, Edwards and Dinsdale, and takes a cross-disciplinary approach to learning more about bacteriophages and exploring their potential for medical usage.
 

 Journal Reference:

1. Bas E. Dutilh, Noriko Cassman, Katelyn McNair, Savannah E. Sanchez, Genivaldo G. Z. Silva, Lance Boling, Jeremy J. Barr, Daan R. Speth, Victor Seguritan, Ramy K. Aziz, Ben Felts, Elizabeth A. Dinsdale, John L. Mokili, Robert A. Edwards. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes. Nature Communications, 2014; 5 DOI: 10.1038/ncomms5498

Courtesy: ScienceDaily