A rare occurrence in the earliest days of a pregnancy produces an unusual and mystifying outcome: Identical twin fetuses are conceived of the same meeting of egg and sperm. And despite their shared DNA, one of the twins has Down syndrome (the most common genetic cause of intellectual impairment), but the other does not.
But these aborted identical twins -- one with an extra copy of chromosome 21 and the other without -- offered scientists a remarkable opportunity: given the twin fetuses' otherwise exact DNA match, how would this one difference translate across the genome?
That natural experiment allowed a group of geneticists from Switzerland, Spain, the Netherlands and France to distill some fundamental insights into how chromosomes -- and the genetic blueprints they contain -- dictate the behavior of cells across the body. They found that when gene expression is altered by, say, an added chromosome, it is altered in consistent patterns in every chromosome, not just the one with the irregularity.
A few things follow from that: First, it lends credence to scientists' long-running suspicion that chromosomes -- between 50 and 100 base pairs of DNA -- may be organized along functional lines, such that certain stretches of a chromosome may hold the genetic blueprint for proteins that work together in some predictable way. If they are organized functionally, they're not random. And if they're not random, they can (someday) be understood.
Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins’ fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of Down’s syndrome and normal littermate mouse fibroblasts also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall position of LADs was not altered in trisomic cells; however, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.
Ebola is one of the scariest viruses on Earth. Along with Marburg and a few other lesser known viruses, it is a member of the Filoviridae family, a nasty group of microbes that causes hemorrhagic fever. Like most viral diseases, patients with hemorrhagic fever will first present with flu-like symptoms. As the disease progresses, patients often bleed from their body orifices, such as their eyes and ears. Death, however, does not result from blood loss, but from shock or organ failure.
Hemorrhagic fevers are not easy to catch. Transmission generally requires prolonged contact with the patient or with his bodily fluids. Mortality rates depend on the particular viral strain. For Ebola, thedeadliest strain is Zaire, which can kill up to 90% of those infected. The worst ever outbreak occurred in Congo in 1976. That year, 318 people were infected and 280 died, a mortality rate of 88%. Currently, an outbreak of Ebola has killed at least 135 people in west Africa. The virus resembles Zaire, but researchers have determined that it is a brand new strain.
Obviously, finding a treatment or cure for such a frightening disease is desirable. With our highly interconnected world, it is only a matter of time before a hemorrhagic fever shows up on our doorstep. (Actually,that's already happened.) Unfortunately, at the present time, there is little that can be done for a victim of Ebola or any other hemorrhagic fever. Mostly, patients are kept hydrated and symptoms are treated as they arise. Other than that, doctors cross their fingers and hope the patient doesn't die.
That may be about to change. In the journal Nature, scientists -- who conducted much of their work in the secretive, high-containment biological laboratory maintained by USAMRIID at Fort Detrick, Maryland -- have reported the discovery of a small molecule that rescues rodents and monkeys from various hemorrhagic fevers. Even more, the drug exhibited activity against a wide range of viruses.
The molecule, named BCX4430, resembles the "A" found in DNA: adenosine. The RNA-based filoviruses also use "A" in their genomes. BCX4430, because it resembles "A", can be accidentally used by the virus when it is trying to grow inside of our cells. For the virus, this is a fatal mistake. BCX4430 blocks further growth and reproduction.
Shouldn't this drug be expected to hurt not only the virus, but humans as well? That would be a reasonable expectation, but for some reason, BCX4430 appears to only hurt the virus. Human cells appear not to be fooled by BCX4430 and do just fine in its presence. The most compelling experiment the research team ran involved the infection of cynomolgus macaque monkeys with deadly Marburg virus. Macaques were given twice daily doses of BCX4430 for 14 days beginning 1 hour, 24 hours, or 48 hours post-infection.
Amazingly, in vitro experiments showed that BCX4430 could potentially work against a wide range of viruses, including SARS, MERS, influenza, dengue, and measles.
Source: TK Warren et al. "Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430." Nature 508: 402-405 (2014). doi:10.1038/nature13027
Advanced Cell Technology is testing a stem-cell treatment for blindness that could preserve vision and potentially reverse vision loss.
A new treatment for macular degeneration is close to the next stage of human testing—a noteworthy event not just for the millions of patients it could help, but for its potential to become the first therapy based on embryonic stem cells.
This year, the Boston-area company Advanced Cell Technology plans to move its stem-cell treatment for two forms of vision loss into advanced human trials. The company has already reported that the treatment is safe (see “Eye Study Is a Small but Crucial Advance for Stem-Cell Therapy”), although a full report of the results from the early, safety-focused testing has yet to be published. The planned trials will test whether it is effective. The treatment will be tested both on patients with Stargardt’s disease (an inherited form of progressive vision loss that can affect children) and on those with age-related macular degeneration, the leading cause of vision loss among people 65 and older.
Although complete data from the trials of ACT’s treatments have yet to be published, the company has reported impressive results with one patient, who recovered vision after being deemed legally blind. Now the company plans to publish the data from two clinical trials taking place in the U.S. and the E.U. in a peer-reviewed academic journal. Each of these early-stage trials includes 12 patients affected by either macular degeneration or Stargardt’s disease.
The more advanced trials will have dozens of participants, says ACT’s head of clinical development, Eddy Anglade. If proved safe and effective, the cellular therapy could preserve the vision of millions affected by age-related macular degeneration. By 2020, as the population ages, nearly 200 million people worldwide will have the disease, estimate researchers. Currently, there are no treatments available for the most common form, dry age-related macular degeneration.
Families with kids aged 2 to 20-something were encouraged by the rabbis to walk around when they needed to, bring their snacks back to their seats, dance to the music or do none of the above if they didn't want to. What didn't I hear? The words "SSSHHHHH!" or "Sit down!"
Franklin College is welcoming 5 high school students with intellectual disabilities to its campus this semester thanks to grant from Indiana University Institute on Disability and Community and its Center on Community Living and Careers.
When people have nerve problems such as those caused by spinal injuries, they can lose the ability to feel when their bladder is full. This means that they don't know when it needs to be emptied, resulting in a build-up of pressure that can damage both the bladder and their kidneys. Now, a tiny sensor may offer a better way of assessing their condition, to see if surgery is required or if medication will suffice.
Presently, in order to observe how well the bladder is functioning, a catheter is inserted into the patient's urethra and used to fill their bladder with saline solution. This is understandably uncomfortable for the patient, plus it's claimed to provide an inaccurate picture of what's going on, as the bladder fills up much more quickly than would normally be the case.
That's why scientists at Norwegian research group SINTEF are proposing replacing the catheters with tiny pressure sensors. The current prototypes can be injected into the bladder directly through the skin, and could conceivably stay in place for months or even years, providing readings without any discomfort, and without requiring the bladder to be filled mechanically.
Patients would be able to move around normally, plus the risk of infection would reportedly be reduced. Currently readings are transmitted from the prototypes via a thin wire that extents from the senor out through the skin, although it is hoped that subsequent versions could transmit wirelessly – perhaps even to the patient's smartphone.
Next month, a clinical trial involving three spinal injury patients is scheduled to begin at Norway's Sunnaas Hospital. Down the road, plans call for trials involving 20 to 30 test subjects.
Although they're currently about to be tested in the bladder, the sensors could conceivably be used to measure pressure almost anywhere in the body.
Universal design is a means of allowing residents of all ability levels to live and function independently. I wish that more architects would embrace the concept so that individuals with disabilities would have a greater access to independent housing.
After years of failed attempts, researchers have successfully generated stem cells from adults. The process could provide a new way for scientists to generate healthy replacements for diseased or damaged cells in patients
After years of failed attempts, researchers have finally generated stem cells from adults using the same cloning technique that produced Dolly the sheep in 1996.
A previous claim that Korean investigators had succeeded in the feat turned out to be fraudulent. Then last year, a group at Oregon Health & Science University generated stem cells using the Dolly technique, but with cells from fetuses and infants.In this case, cells from a 35-year-old man and a 75-year-old man were used to generate two separate lines of stem cells. The process, known as nuclear transfer, involves taking the DNA from a donor and inserting it into an egg that has been stripped of its DNA. The resulting hybrid is stimulated to fuse and start dividing; after a few days the “embryo” creates a lining of stem cells that are destined to develop into all of the cells and tissues in the human body. Researchers extract these cells and grow them in the lab, where they are treated with the appropriate growth factors and other agents to develop into specific types of cells, like neurons, muscle, or insulin-producing cells. Reporting in the journal Cell Stem Cell, Dr. Robert Lanza, chief scientific officer at biotechnology company Advanced Cell Technology, and his colleagues found that tweaking the Oregon team’s process was the key to success with reprogramming the older cells. Like the earlier team, Lanza’s group used caffeine to prevent the fused egg from dividing prematurely. Rather than leaving the egg with its newly introduced DNA for 30 minutes before activating the dividing stage, they let the eggs rest for about two hours. This gave the DNA enough time to acclimate to its new environment and interact with the egg’s development factors, which erased each of the donor cell’s existing history and reprogrammed it to act like a brand new cell in an embryo.
The team, which included an international group of stem cell scientists, used 77 eggs from four different donors. They tested their new method by waiting for 30 minutes before activating 38 of the resulting embryos, and waiting two hours before triggering 39 of them. None of the 38 developed into the next stage, while two of the embryos getting extended time did. “There is a massive molecular change occurring. You are taking a fully differentiated cell, and you need to have the egg do its magic,” says Lanza. “You need to extend the reprogramming time before you can force the cell to divide.”
While a 5% efficiency may not seem laudable, Lanza says that it’s not so bad given that the stem cells appear to have had their genetic history completely erased and returned to that of a blank slate. “This procedure works well, and works with adult cells,” says Lanza.
The results also teach stem cell scientists some important lessons. First, that the nuclear transfer method that the Oregon team used is valid, and that with some changes it can be replicated using older adult cells. “It looks like the protocols we described are real, they are universal, they work in different hands, in different labs and with different cells,” says Shoukhrat Mitalopov, director of the center for embryonic cell and gene therapy at Oregon Health & Science University, and lead investigator of that study.
VIDEO: Breakthrough in Cloning Human Stem Cells: Explainer
Partially paralyzed man walks again thanks to new technology WBTV Programmed using microprocessors and sensors in real time, the C-Brace is new orthotic technology specifically developed to help people like Walker walk and avoid life in a wheelchair.
A lantern and flashlight wheelchair accessory that can clamp onto a wheelchair and provide night cruising light or hands free lighting for almost anything. The post Clamp On Lantern and Flashlight Wheelchair Accessory?
KU student designs Ultramouse to help paralyzed uncle Topeka Capital Journal Henry Clever, a University of Kansas senior majoring in mechanical engineering, recently designed Ultramouse, a system of sensors that can be attached behind and beside...