HOW LIZARDS REGENERATE THEIR TAILS: RESEARCHERS DISCOVER GENETIC ‘RECIPE’
Finding may impact future therapies for spinal cord injuries -regeneration of limbs in humans
From FMS Global News Desk of Jeanne Hambleton Released: 20-Aug-2014
Source : Arizona State University College of Liberal Arts and Sciences Citations PLOS ONE
Newswise — TEMPE, Ariz. – By understanding the secret of how lizards regenerate their tails, researchers may be able to develop ways to stimulate the regeneration of limbs in humans. Now, a team of researchers from Arizona State University is one step closer to solving that mystery. The scientists have discovered the genetic “recipe” for lizard tail regeneration, which may come down to using genetic ingredients in just the right mixture and amounts.
An interdisciplinary team of scientists used next-generation molecular and computer analysis tools to examine the genes turned on in tail regeneration. The team studied the regenerating tail of the green anole lizard (Anolis carolinensis), which when caught by a predator, can lose its tail and then grow it back.
The findings are published today in the journal PLOS ONE.
“Lizards basically share the same toolbox of genes as humans,” said lead author Kenro Kusumi, professor in ASU’s School of Life Sciences and associate dean in the College of Liberal Arts and Sciences.
“Lizards are the most closely-related animals to humans that can regenerate entire appendages. We discovered that they turn on at least 326 genes in specific regions of the regenerating tail, including genes involved in embryonic development, response to hormonal signals and wound healing.”
Other animals, such as salamanders, frog tadpoles and fish, can also regenerate their tails, with growth mostly at the tip. During tail regeneration, they all turn on genes in what is called the ‘Wnt pathway’ — a process that is required to control stem cells in many organs such as the brain, hair follicles and blood vessels. However, lizards have a unique pattern of tissue growth that is distributed throughout the tail.
“Regeneration is not an instant process,” said Elizabeth Hutchins, a graduate student in ASU’s molecular and cellular biology program and co-author of the paper.
“In fact, it takes lizards more than 60 days to regenerate a functional tail. Lizards form a complex regenerating structure with cells growing into tissues at a number of sites along the tail.”
“We have identified one type of cell that is important for tissue regeneration,” said Jeanne Wilson-Rawls, co-author and associate professor with ASU’s School of Life Sciences.
“Just like in mice and humans, lizards have satellite cells that can grow and develop into skeletal muscle and other tissues.”
“Using next-generation technologies to sequence all the genes expressed during regeneration, we have unlocked the mystery of what genes are needed to regrow the lizard tail,” said Kusumi.
“By following the genetic recipe for regeneration that is found in lizards, and then harnessing those same genes in human cells, it may be possible to regrow new cartilage, muscle or even spinal cord in the future.”
The researchers hope their findings will help lead to discoveries of new therapeutic approaches to spinal cord injuries, repairing birth defects, and treating diseases such as arthritis.
The research team included Kusumi, Hutchins, Wilson-Rawls, Alan Rawls, and Dale DeNardo from ASU School of Life Sciences, Rebecca Fisher from ASU School of Life Sciences and the University of Arizona College of Medicine Phoenix, Matthew Huentelman from the Translational Genomic Research Institute, and Juli Wade from Michigan State University. This research was funded by grants from the National Institutes of Health and Arizona Biomedical Research Commission.
ASU’s School of Life Sciences is an academic unit of the College of Liberal Arts and Sciences.
Arizona State University is the largest public research university in the United States under a single administration, with total student enrollment of more than 70,000 in metropolitan Phoenix, the nation’s sixth-largest city. ASU is creating a new model for American higher education, an unprecedented combination of academic excellence, entrepreneurial energy and broad access. This New American University is a single, unified institution comprising four differentiated campuses positively impacting the economic, social, cultural and environmental health of the communities it serves. Its research is inspired by real-world application, blurring the boundaries that traditionally separate academic disciplines. ASU champions intellectual and cultural diversity, and welcomes students from all 50 states and more than 120 nations.
(WOW what an exciting development for soldiers who lost limbs in war and those born less fortunate than ourselves. What great excitement there must have been in that laboratory! Well done to those involved.)
SINGLE GENE CONTROLS JET LAG
Salk researchers discover a master gene responsible for sleep and wake cycles, offering hope for a drug that could help reset sleep
From the FMS Global News Desk of Jeanne Hambleton Released: 13-Aug-2014
Source: Salk Institute for Biological Studies Citations eLife
Newswise — LA JOLLA–Scientists at the Salk Institute for Biological Studies have identified a gene that regulates sleep and wake rhythms.
The discovery of the role of this gene, called Lhx1, provides scientists with a potential therapeutic target to help night-shift workers or jet lagged travelers adjust to time differences more quickly. The results, published in eLife, can point to treatment strategies for sleep problems caused by a variety of disorders.
“It’s possible that the severity of many dementias comes from sleep disturbances,” says Satchidananda Panda, a Salk associate professor who led the research team. “If we can restore normal sleep, we can address half of the problem.”
Every cell in the body has a “clock” – an abundance of proteins that dip or rise rhythmically over approximately 24 hours. The master clock responsible for establishing these cyclic circadian rhythms and keeping all the body’s cells in sync is the suprachiasmatic nucleus (SCN), a small, densely packed region of about 20,000 neurons housed in the brain’s hypothalamus.
More so than in other areas of the brain, the SCN’s neurons are in close and constant communication with one another. This close interaction, combined with exposure to light and darkness through vision circuits, keeps this master clock in sync and allows people to stay on essentially the same schedule every day. The tight coupling of these cells also helps make them collectively resistant to change. Exposure to light resets less than half of the SCN cells, resulting in long periods of jet lag.
In the new study, researchers disrupted the light-dark cycles in mice and compared changes in the expression of thousands of genes in the SCN with other mouse tissues. They identified 213 gene expression changes that were unique to the SCN and narrowed in on 13 of these that coded for molecules that turn on and off other genes. Of those, only one was suppressed in response to light: Lhx1.
“No one had ever imagined that Lhx1 might be so intricately involved in SCN function,” says Shubhroz Gill, a postdoctoral researcher and co-first author of the paper. Lhx1 is known for its role in neural development: it’s so important, that mice without the gene do not survive. But this is the first time it has been identified as a master regulator of light-dark cycle genes.
By recording electrical activity in the SCN of animals with reduced amounts of the Lhx1 protein, the researchers saw that the SCN neurons weren’t in sync with one another, despite appearing rhythmic individually.
“It was all about communication–the neurons were not talking to each other without this molecule,” says Ludovic Mure, a postdoctoral researcher and an author on the paper. A next step in the work will be to understand exactly how Lhx1 affects the expression of genes that creates this synchronicity.
Studying a mouse version of jet lag–an 8-hour shift in their day-night cycle–the scientists found that those with little or no Lhx1 readjusted much faster to the shift than normal mice. This suggests that because these neurons are less in sync with one another, they are more easily able to shift to a new schedule, though it is difficult for them to maintain that schedule, Panda says.
These mice also exhibited reduced activity of certain genes, including one that creates vasoactive intestinal peptide or Vip, a molecule that has important roles in development and as a hormone in the intestine and blood. In the brain, Vip affects cell communication, but nobody had known that Lhx1 regulated it until now, Panda says. Interestingly, the team also found that adding Vip restored cell synchrony in the SCN.
“This approach helped us to close that knowledge gap and show that Vip is a very important protein, at least for SCN,” Panda says. “It can compensate for the loss of Lhx1.”
On the other hand, cutting back on Vip could be another way to treat jet lag. Vip could be an even easier drug target compared with Lhx1 because Vip is secreted from cells rather than inside cells, Panda says. “If we find a drug that will block the Vip receptor or somehow break down Vip, then maybe that will help us reset the clock much faster,” he adds.
The new results take the group a step closer to their goal of creating cell regenerative therapies that restore the SCN and ameliorate sleep problems. The scientists have made their gene expression data available through a searchable web interface at http://scn.salk.edu, giving other researchers a handy way to explore the effect of light and dark in genes in the SCN and other tissues.
Other researchers on the study were Megumi Hatori, now at Keio University School of Medicine in Tokyo, and Martyn Goulding and Dennis D.M. O’Leary of Salk.
The work was supported by fellowships from The Japan Society for the Promotion of Science, Messinger Healthy Living, the Fyssen and Catharina Foundation, the Mary K. Chapman Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health, the Hearst Foundation and the Glenn Foundation.
About the Salk Institute for Biological Studies:
The Salk Institute for Biological Studies is one of the world’s preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer’s, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.
Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, MD, the Institute is an independent nonprofit organization and architectural landmark.
(ANOTHER FANTASTIC DEVELOPMENT for fibromites who have problems sleeping and the elderly who we were learn have increasing sleep problems with age.)
TO CONTROL DRINKING, USE A RULE OF THUMB
From the FMS Global News Desk of Jeanne Hambleton Posted on August 22, 2014 by Stone Hearth News
Newswise — AMES, Iowa – Sticking to a general rule of pouring just a half glass of wine limits the likelihood of over consumption, even for men with a higher body mass index. That is the finding of a new Iowa State and Cornell University study to be published in a forthcoming issue of the International Journal of Drug Policy.
Laura Smarandescu, lead author and an assistant professor of marketing at Iowa State, says the research team looked at a variety of factors to understand and control over pouring. Researchers found BMI affected how much men poured, but had no influence on women. However, people who used a “rule of thumb,” such as a half-glass rule or a two-fingers-from-the-top rule when pouring wine, poured less regardless of BMI or gender.
“About 70 percent of the people in the sample used the half-glass rule, and they poured significantly less by about 20 percent,” Smarandescu said.
“It is a big difference. We would suggest using a rule of thumb with pouring because it makes a big difference in how much people pour and prevents them from over drinking.”
Men with a higher BMI, who did not use a rule of thumb, poured more – 31 percent more for men considered overweight or obese and 26 percent more for men at the midpoint of the normal BMI range. While BMI did not affect how much women poured, those at the midpoint of the normal BMI poured 27 percent less when using the half-glass rule than those who did not.
Researchers were not surprised to find men poured more than women, which is consistent with other studies of alcohol consumption. However, they did not expect the half glass rule would be an exception to men pouring more.
“In this study, we had every expectation that men would always pour more than women, no matter what. But what we found is that the rule of thumb effect is so strong that men using a rule of thumb at all levels of BMI actually poured less than women who were not using a rule of thumb,” said Doug Walker, an assistant professor of marketing at Iowa State.
Researchers asked 74 college students and staff to pour wine in a variety of settings so that they could control for the size, shape and color of the glass, as well as if wine is poured with a meal. They poured both red and white wine from bottles with different levels of fullness. Participants were told to pour as much as wine as they normally would in one setting.
Impact of social norms
Drinking is more socially acceptable for men than women, which is one explanation for why BMI did not have the same effect on women, researchers said. Women are often more conscious of how much they are pouring and will pour less.
“Women are more likely to socially compare with other women. They are aware that drinking is not as socially acceptable for women as it is for men, although it is becoming more acceptable than it has been in the past. But for men there is still more of a culture of drinking and pouring more,” Smarandescu said.
The study looked only at pours, not consumption. However, researchers point to previous studies that show serving size is linked with overeating. Free pouring wine increases the tendency to over consume because it is not as easily measured as other types of beer or spirits.
“It is essential for all drinkers, especially men of higher BMIs, to have a rule of thumb for self-serving, because eye-balling a serving size is a difficult task and will often lead people to pour too much,” said Brian Wansink, a professor of marketing at Cornell.
“Next time you open a bottle, serve yourself a half glass – regardless of the size of your glass—and you will be less likely to accidentally drink too much.”
(Let us hope these folks pouring all these half glasses of wine are not drink driving to get home.) Back tomorrow Jeanne