PUBLIC RELEASE DATE:

18-Jul-2014

Contact: Charles Casey charles.casey@ucdmc.ucdavis.edu 916-734-9048 University of California - Davis Health System

(SACRAMENTO, Calif.) Researchers from UC Davis School of Medicine and Shriners Hospitals for Children Northern California have identified a group of cells in the brain that they say plays an important role in the abnormal neuron development in Down syndrome. After developing a new model for studying the syndrome using patient-derived stem cells, the scientists also found that applying an inexpensive antibiotic to the cells appears to correct many abnormalities in the interaction between the cells and developing neurons.

The findings, which focused on support cells in the brain called astroglial cells, appear online today in Nature Communications.

"We have developed a human cellular model for studying brain development in Down syndrome that allows us to carry out detailed physiological studies and screen possible new therapies," said Wenbin Deng, associate professor of biochemistry and molecular medicine and principal investigator of the study. "This model is more realistic than traditional animal models because it is derived from a patient's own cells."

Down syndrome is the most common chromosomal cause of mild to moderate intellectual disabilities in the United States, where it occurs in one in every 691 live births. It develops when a person has three copies of the 21st chromosome instead of the normal two. While mouse models have traditionally been used in studying the genetic disorder, Deng said the animal model is inadequate because the human brain is more complicated, and much of that complexity arises from astroglia cells, the star-shaped cells that play an important role in the physical structure of the brain as well as in the transmission of nerve impulses.

"Although neurons are regarded as our 'thinking cells,' the astroglia have an extremely important supportive role," said Deng. "Astroglial function is increasingly recognized as a critical factor in neuronal dysfunction in the brain, and this is the first study to show its importance in Down syndrome."

Creating a unique human cellular model

To investigate the role of astroglia in Down syndrome, the research team took skin cells from individuals with Down syndrome and transformed them into stem cells, which are known as induced pluripotent stem cells (iPSC). The cells possess the same genetic make-up as the donor and an ability to grow into different cell types. Deng and his colleagues next induced the stem cells to develop into separate pure populations of astroglial cells and neurons. This allowed them to systematically analyze factors expressed by the astroglia and then study their effects on neuron development.

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'Support' cells in brain play important role in Down syndrome

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Let #39;s Play The Sims 3 - Perfect Genetics Challenge: Cowgirl and Horse Edition Episode 21
Come join me on my latest journey into the complex world of sims 3 genetics, as I try to get perfect foals and perfect children. Will I succeed in getting pe...

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Research Minute: Anne Kwitek, Genetics
Anne Kwitek is a genetics researcher at the University of Iowa. Her research is looking at how DNA changes can make individual #39;s more suseptible to common di...

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Conservation Genetics and the Search for a New Species | Todd Disotell | TEDxNYU
This talk was given at a local TEDx event, produced independently of the TED Conferences. Todd Disotell, a biological anthropologist, investigates primate and human evolution. In this talk,...

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Proxy Plays Arkham: Origins #2 #39;Genetics #39;
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Health: An Important Development For Heart Patients Who Need Pacemakers
Stephanie Stahl has more on what scientists are calling a new era of gene therapy. Official Site: http://philadelphia.cbslocal.com/ Subscribe on YouTube: http://www.youtube.com/cbsphilly Like...

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DNA animation
Blender animation for TV news story. About Gene therapy. Blender internal render, over sampled 200% to reduce aliasing. Fake Depth of field effect in compositing.

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Newswise Learning the role of immune system cells in healthy digestive tracts and how they interact with neighboring nerve cells may lead to new treatments for irritable bowel syndrome (IBS). Researchers from Penn State College of Medicine, in collaboration with other scientists, have reported the role of macrophages in regulating the contractions of the colon to push digested material through the digestive tract.

The muscular lining of the intestine contains a distinct kind of macrophage, an immune system cell that helps fight infections. The role of these cells in normal colon function is not known, although they have been linked to inflammation after abdominal surgery.

Very little is known about the function of muscularis macrophages, mainly because these cells are difficult to isolate from intestinal tissue, said Milena Bogunovic, assistant professor of microbiology and immunology.

Digested material is moved through the intestines by the contraction and relaxation of intestinal muscles. The pattern and frequency of these contractions are controlled by the signals from the intestinal nervous system. In patients with diseases like IBS, the signals are overactive and stimulation is exaggerated.

The researchers developed a method to deplete muscularis macrophages in the intestines of mice to determine their function. They report their findings in Cell.

After macrophage depletion, we observed that the normal intestinal movements are irregular, probably because the muscular contractions were poorly coordinated, suggesting that intestinal movements are regulated by macrophages, Bogunovic said.

After confirming the role of the macrophages in the function of the digestive tract, the researchers looked for how the regulation happens. They compared the genetic code of different types of macrophages to find non-immune genes highly active in muscularis macrophages, identifying bone morphogenetic protein 2. BMP2 is one of a family of proteins thought to control organ development.

Blocking the effect of BMP2 mirrored the effects of the macrophage removal, confirming that the protein is used for regulation of intestinal movements. The BMP2 is used by neighboring nerve cells, intestinal neurons, which in turn secrete a protein called colony stimulatory factor 1 (CSF1) that supports macrophages.

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The Future of Oncology: Drugs, Genetic Testing and Personalized Medicine
Dr. Richard Schilsky discusses the curious history of cancer treatments, and their future direction based on new discoveries, and advances in genomics and pe...

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Spinal Cord BBQ July 15, 2014
Henry #39;s award from Spinal Cord Injury Ontario - BBQ.

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Doug Mowat Memorial Golf Tournament 2014
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Creating a job description
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Regenerative Medicine at Healthpointe
http://jointreliefclinic.com http://healthpointemd.net/regenerative_medicine.shtml (714) 367-5046 Using the cells found in the human body that naturally restore tissue, regenerative medicine...

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A temporary drop-in clinic could be set up in Dundee for people to register as bone marrow donors.

Annie Irving, president of the Marrow Dundee student society, has offered to organise the clinic after more than 100 Tele readers registered to help those suffering from blood cancers.

The fantastic response is the result of an overflow of compassion towards baby Faith Cushnie, who, at nine months old, is losing her battle with leukaemia after her donor backed out.

A total of 142 people in Tayside have registered with Anthony Nolan since the article and 873 have visited the charitys website.

Annie, who studies medicine at Dundee University, said: A personal story reaches people more than numbers and statistics and the fact that the little girls chance has been taken away from her because there arent enough people on the register is very sad. Peoples responses have been brilliant though.

The society is affiliated to charity Anthony Nolan, which maintains a register of potential bone marrow donors. Stem cells from bone marrow are used to treat cancers like leukaemia, lymphoma and myeloma and blood disorders such as sickle cell disease.

Drop-in clinics allow people to take a spit test to determine whether they are suitable to be a donor. They also have the opportunity to speak to a trained counsellor.

Annie explained: When we counsel people we tell them about the likelihood of being called up and the process of donating.

Annie hopes to be able to organise a clinic as soon as possible and is in the process of contacting venues to find somewhere to host the drop-in.

She said: I want to have a clinic soon and encourage more people to join the register. Donating bone marrow is a chance to save a life.

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Bid for Dundee bone marrow clinic to meet donor demand

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Newswise Buffalo, NY BlueCross BlueShield of Western New York today has redesignated Roswell Park Cancer Institute (RPCI) as a Blue Distinction Center for delivering quality transplant care as part of the Blue Distinction Centers for Specialty Care program. Approximately 100 Blue Distinction Centers for Transplants have been designated in the United States, with only four located in New York State.

Blue Distinction Centers are medical facilities shown to deliver quality specialty care based on objective, transparent measures for patient safety and health outcomes that were developed with input from the medical community. To receive a Blue Distinction Centers for Transplants designation, medical facilities must demonstrate success in meeting patient safety criteria as well as transplant-specific quality measures (including survival metrics). RPCI received the same Blue Distinction Center designation in 2011.

Blood and marrow hematopoietic stem-cell transplants, also known as bone-marrow transplants, are a common approach for treating many types of hematologic cancers, including forms of leukemia, lymphoma and multiple myeloma. They involve the transplant of blood or bone marrow stem cells from a donor or from the patients themselves as a way of sparing the patient the toxic effects of intensive chemotherapy and/or radiation.

Because blood and marrow transplant is such a highly complex procedure, a patients medical needs before, during and after a transplant procedure are extensive and labor-intensive, said Philip McCarthy, MD, Director of RPCIs Blood & Marrow Transplant Program. Given that context, were especially proud to once again earn Blue Distinction for our transplant program from BlueCross BlueShield.

More Research shows that Blue Distinction Centers demonstrate better quality and improved outcomes for patients with higher survival rates compared with their peers.

We are pleased that RPCI has been recognized for their quality transplant care, said Dr. Thomas Schenk, Senior Vice President and Chief Medical Officer, BlueCross BlueShield of Western New York. As part of the BCBS network they are a valued and once again nationally recognized provider of quality care.

Although rare, the number of transplants including heart, lung, liver, pancreas and bone marrow/blood stem cell in the nation have increased in recent years. There were 28,954 transplant procedures performed in 2013 compared to 28,052 in 2012. Today, more than 123,000 people are awaiting organ donations for transplants, according to the U.S. Department of Health & Human Services.

In 2006, the Blue Distinction Centers for Specialty Care program was developed to help patients find quality providers for their specialty care needs while encouraging healthcare professionals to improve the care they deliver.

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Roswell Park Recognized for Quality in Bone Marrow Transplant Care

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PUBLIC RELEASE DATE:

17-Jul-2014

Contact: Tom Oswald tom.oswald@cabs.msu.edu 517-432-0920 Michigan State University

Not unlike looking for the proverbial needle in a haystack, a team of Michigan State University researchers have found a gene that could be key to the development of stem cells cells that can potentially save millions of lives by morphing into practically any cell in the body.

The gene, known as ASF1A, was not discovered by the team. However, it is at least one of the genes responsible for the mechanism of cellular reprogramming, a phenomenon that can turn one cell type into another, which is key to the making of stem cells.

In a paper published in the journal Science, the researchers describe how they analyzed more than 5,000 genes from a human egg, or oocyte, before determining that the ASF1A, along with another gene known as OCT4 and a helper soluble molecule, were the ones responsible for the reprogramming.

"This has the potential to be a major breakthrough in the way we look at how stem cells are developed," said Elena Gonzalez-Munoz, a former MSU post-doctoral researcher and first author of the paper. "Researchers are just now figuring out how adult somatic cells such as skin cells can be turned into embryonic stem cells. Hopefully this will be the way to understand more about how that mechanism works."

In 2006, an MSU team identified the thousands of genes that reside in the oocyte. It was from those, they concluded, that they could identify the genes responsible for cellular reprogramming.

In 2007, a team of Japanese researchers found that by introducing four other genes into cells, stem cells could be created without the use of a human egg. These cells are called induced pluripotent stem cells, or iPSCs.

"This is important because the iPSCs are derived directly from adult tissue and can be a perfect genetic match for a patient," said Jose Cibelli, an MSU professor of animal science and a member of the team.

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Discovery may make it easier to develop life-saving stem cells

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UNDATED (WJRT) - (07/17/14) - Would you poke your skin with pins if it meant you'd look years younger?

Last year, Americans underwent more than 11 million cosmetic procedures, and they spent nearly $12 billion on skin rejuvenation. Everyone wants their skin to look younger, healthier and better, but some are taking it to an extreme.

Cheri Kovacsev's face is dripping with blood - and she wouldn't have it any other way.

"I'm hoping to achieve smaller pores, the fine lines around my lips to improve over this process," she said.

Licensed paramedical aesthetician, Amaris Centofanti, is performing rejuvapen micro-needling.

"After you are done with the treatment, collagen elastin kicks in to heal the skin, so in a few days, your skin starts to look more flawless," she said.

Some, like professor of dermatology James Spencer, aren't sold on micro-needling - which costs about $350 a pop.

"There was just a study in the journal of the American Medical Association Dermatology, Jama Dermatology, last month, of three cases of allergy to the medication to the serum that was put on after micro-needling," he said.

Some other extreme beauty treatments:

- The bee venom facial. The theory is the venom tightens skin by pumping up collagen. It costs about $130.

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Bizarre beauty trends: are they safe?

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Genes for swatting tiger mosquitoes, defanging brown tree snakes, and deporting Asian carp, all nasty invasive species, sound like a swell idea. But the latest idea in eradicationgenetic engineeringposes its own risks, warn biotechnology experts.

Invasive species wreak havoc worldwide, disrupting native ecosystems and inflicting more than $120 billion in damages annually in the U.S. alone. Many economicallyand environmentallydamaging species, such as those mosquitoes, snakes, and carp, defy removal with existing technology.

But there is good news. "Gene drives"which could trigger a precipitous decline in invasive species by tinkering with their genetic machineryhave arrived as a fast-maturing technology, an international team of scientists announced on Thursday.

"Once an invasive species arrives in a new habitat and is driving native species extinct, we don't necessarily have a lot of solutions to that. Gene drive technology could potentially cause local extinction [of the invasive species] and restore the original ecosystem," says Kevin Esvelt, a genetic engineer at Harvard University and an author of tandem papers published this week in Science and eLife.

But he and his colleagues warn that we should tread cautiously; otherwise, the new technology may blow up in our face. "We want to make sure this technology is used responsibly to solve problems facing humanity and the natural world," Esvelt says. (See "Why the 67 Giant Snails Seized in L.A. Are Harmful.")

How It Works

The technology starts by identifying a genetic alteration that could reduce pesticide resistance, hinder a population's ability to reproduce, or have some other desirable impact on the target species.

Scientists could then insert that alteration into the genome of an invasive species, but there is no guarantee that it will propagate.

This is where the gene drives come in. Essentially, they act as chauffeurs that can "drive" a genetic alteration through a population, says Esvelt.

In most animals, there are two versions of a gene and each one has a 50-50 chance of being passed on to the next generation.

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Genetic Engineering to the Rescue Against Invasive Species?

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Researcher Frdric Choulet explains why mapping the bread genome is so important and discusses sequencing wheat chromosome 3B. (INRA)

Scientists announced Thursday that they are approaching a milestone in humanitys ability to improve bread wheat.

One of the most common and most versatile crops on the planet the main food staple for a third of the world population wheat is remarkably good at adapting to change. But efforts to grow higher-yielding, more nutritious and more resilient wheat in response to population growth and climate change have been slow for one simple reason. Its genes are a big, complicated mess.

Many scientists thought that it would be impossible to map the genome of wheat to figure out how its genes are ordered so that specific traits can be more quickly identified. But a group made up of scientists, breeders and growers say that theyre more than halfway there and that an entire sequence is on the horizon.

Genome sequencing has revolutionized the process of breeding corn and rice, experts said, and is especially important given the stress that climate change will put on the food supply as the worlds population booms.

Human civilization rests on a small handful of crops, all of which were developed with much more stable weather conditions than we see now, said Patrick Schnable, an Iowa State University professor who worked on the genome sequencing of corn. In a world with climate change, we need to help those crops adapt quickly. And to do that, he said, one needs the genome sequence.

I was told by a breeder that it was the single most valuable thing the government has ever done for them, Schnable said. The genetic information has been used to increase crop yields and make crops more resilient to stresses such as pests and weather change.

The same has been true for rice. Its accelerated the discovery of the genes involved in many traits, including those for higher yield and disease resistance, said Jan E. Leach, a Colorado State University professor who is not involved in the study. Its always boggled my mind how ridiculous it is to not have [a complete genome] for wheat, she said, so this is great news.

Thursdays announcement reported that about half of bread wheats genome has been sequenced, which might not sound impressive. But until recently, scientists had something like 5 percent of the information, said Kellye Eversole, executive director of the International Wheat Genome Sequencing Consortium (IWGSC), which organized the research.

She compared the sequencing thus far to a partially completed map. After starting with an empty map and a list of roads, she said, the researchers now have about half the highways in place. Its not very well ordered, she said. You might know theres a Route 1, and that its in Virginia, but you dont know exactly where it is. But its a guide, and its accelerating us towards that complete map.

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Scientists unlock the genetic secrets of bread wheat

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PUBLIC RELEASE DATE:

17-Jul-2014

Contact: Kathryn Ruehle kruehle@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

Splice-Switching Oligonucleotide Therapeutics Is Promising New Method for Editing Gene Transcripts

New Rochelle, NY, July 17, 2014In splice-switching, an innovative therapeutic approach, targeted oligonucleotide drugs alter the editing of a gene transcript to produce the desired form of a protein. Developments in this rapidly advancing field have already led to promising treatments for such diseases as Duchenne Muscular Dystrophy and spinal muscular atrophy, as described in an article in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the Human Gene Therapy website.

In "Development of Therapeutic Splice-Switching Oligonucleotides," Petra Disterer and coauthors from University College London, University of London, and Queen Mary University of London, UK, and Medical University of Warsaw, Poland, present an overview of the many possible therapeutic applications for splice-switching oligonucleotides. The authors discuss the design and chemical modification of these novel compounds to increase their stability and effectiveness, and emphasize the need to develop efficient solutions on a case by case basis.

"This is an emerging therapeutic area with promising clinical results," says James M. Wilson, MD, PhD, Editor-in-Chief of Human Gene Therapy, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.

###

About the Journal

Human Gene Therapy, the official journal of the European Society of Gene and Cell Therapy, British Society for Gene and Cell Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies, is an authoritative peer-reviewed journal published monthly in print and online. Human Gene Therapy presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Its sister journals, Human Gene Therapy Methods, published bimonthly, focuses on the application of gene therapy to product testing and development, and Human Gene Therapy Clinical Development, published quarterly, features data relevant to the regulatory review and commercial development of cell and gene therapy products. Tables of content for all three publications and a free sample issue may be viewed on the Human Gene Therapy website.

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Splice-switching oligonucleotide therapeutics is new method for editing gene transcript

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PUBLIC RELEASE DATE:

17-Jul-2014

Contact: Jeannette Spalding jeannette.spalding@case.edu 216-368-3004 Case Western Reserve University

The mysterious condition once known as "water on the brain" became just a bit less murky this week thanks to a global research group led in part by a Case Western Reserve researcher. Professor Anthony Wynshaw-Boris, MD, PhD, is the co-principal investigator on a study that illustrates how the domino effect of one genetic error can contribute to excessive cerebrospinal fluid surrounding the brains of mice a disorder known as hydrocephalus. The findings appear online July 17 in the journal Neuron.

Cerebrospinal fluid provides a cushion between the organ and the skull, eliminating waste and performing other functions essential to neurological health. Within the brain there are four spaces or ventricles where cerebrospinal fluid flows. Hydrocephalus can be damaging when excessive cerebrospinal fluid widens spaces between ventricles and creates pressure to brain tissue. In humans, hydrocephalus can cause a host of neurological ailments: impairment of balance and coordination, memory loss, headaches and blurred vision, and even damage to the brain.

"Most of the time, hydrocephalus is caused by some sort of physical blockage of the flow of cerebrospinal fluid, so called obstructive hydrocephalus. We demonstrated instead that malfunction of specific genes the Dishevelleds (Dvl genes) triggered hydrocephalus in our mouse models. These genes regulate the precise placement and alignment of cilia within ependymal cells that move cerebrospinal fluid throughout the brain," said Wynshaw-Boris, MD, PhD, James H. Jewell MD '34 Professor of Genetics and Chair, Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine. "This discovery paves the way for more focused research to determine if similar mechanisms can cause hydrocephalus in humans."

Scientists are still at the most nascent stages of understanding different causes and kinds of hydrocephalus. In some instances, the root sources are genetic; in others, the fluid accumulation is attributed to complications of premature birth. This project illuminates one way in which genetic influences contribute to the condition.

Wynshaw-Boris began this collaborative research while a professor in pediatrics at the Institute for Human Genetics and the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at the University of California at San Francisco (UCSF) before coming to Case Western Reserve in June 2013. For this hydrocephalus project, he joined fellow principal co-investigator, Arturo Alvarez-Buylla, PhD, professor of neurological surgery, and the Heather and Melanie Muss Endowed Chair, Department of Neurological Surgery, UCSF, in conducting research that proved in mice that Dvl genes regulate the placement and polarity of cilia in ependymal cells that line the ventricles of the brain.

A cilium is a slender protuberance projecting from many cells. In the ependymal cells, multiple cilia protrude from each cell as a bundle or patch, which resembles a horse's tail when beating to move cerebrospinal fluid efficiently. Each cilium must be anchored, sized and shaped correctly, properly placed and aligned in relation to other cilia within the same cell, and the alignment of cilia between cells is also necessary so that the cilia beat with precision to achieve proper movement of fluid in the right direction. It is all about excellent organization: the wrong size, shape or angle of rotation of the bundle of cilia will impede the smooth and appropriate directional flow of the cerebrospinal fluid.

The work in mice by Shinya Ohata, PhD, and Jin Nakatani, PhD, co-first authors who worked in the Alvarez-Buylla and Wynshaw-Boris labs, respectively, and their colleagues demonstrated how normal versus Dvl-deficient mice fared in terms of cilia function. They examined cilia from the ependymal cells of normal mice and found the cilia to be well organized and correctly placed within and between ependymal cells. Investigators even viewed in real time through fluorescent imaging the intricacy with which well-orchestrated cilia swayed to move fluid along in a normal fashion.

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International research team discovers genetic dysfunction connected to hydrocephalus

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Simple Mendelian genetics problem
Plant Breeding as a Hobby Breeding plants to create new varieties and improve upon old ones is a hobby that nearly everyone can engage in. The crossing techniques are easy to learn and you...

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Genetics of color blindness
Can a female get color-blindness from her father #39;s side? The quick answer is that yes, a female can get a copy of the gene that leads to colorblindness from her father. In fact, the odds...

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Dr. Sharon Savage on the Genetics and Genomics of Bone Marrow Failure Disease
Research Themes and Highlights for Patients from the 2014 Scientific Symposium. Genetics and Genomics of Bone Marrow Failure Disease.

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By Dennis Thompson HealthDay Reporter

WEDNESDAY, July 16, 2014 (HealthDay News) -- Researchers say they've found a way to transform ordinary pig heart muscle cells into a "biological pacemaker," a feat that might one day lead to the replacement of electronic pacemakers in humans.

"Rather than having to undergo implantation with a metallic device that needs to be replaced regularly and can fail or become infected, patients may someday be able to undergo a single gene injection and be cured of slow heart rhythm forever," said senior study author Dr. Eugenio Cingolani, director of the Cedars-Sinai Heart Institute's Cardiogenetics-Familial Arrhythmia Clinic, in Los Angeles.

Using gene therapy, the researchers altered a peppercorn-sized area in the heart muscle of pigs to create a new "sino-atrial node" -- the bundle of neurons that normally serves as the heart's natural pacemaker.

The technique kept alive a handful of pigs suffering from complete heart block, a condition in which the heart beats very slowly or not at all due to problems in the heart's electrical system.

The biological pacemaker also appeared to function as well as an original sino-atrial node and better than typical electronic pacemakers, said study co-author Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute, in Los Angeles.

"When we exercise, our hearts go faster. When we rest, our hearts slow down," Marban said. "The pigs with the biological pacemaker faithfully reproduced these responses, which were absent in 'control' pigs that had been treated only with an electronic pacemaker."

About 300,000 electronic pacemakers are placed in humans in the United States each year, at an annual cost of $8 billion, Marban said. They work by sending electrical pulses to the heart if it is beating too slowly or if it misses a beat.

The key to the new procedure is a gene called TBX18, which converts ordinary heart cells into specialized sino-atrial node cells, Marban said.

The heart's sino-atrial node initiates the heart beat like a metronome, using electric impulses to time the contractions that send blood flowing through people's arteries and veins, the scientists explained. People with abnormal heart rhythms suffer from a defective sino-atrial node.

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Scientists Use Gene Therapy to Create 'Biological Pacemaker' in Pig Hearts

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