Gene silencing could be behind induced pluripotent stem cells” limitations

April 26, 2010 By Leave a Comment

London, Apr 26 (ANI): Getting closer to generate any type of cells and tissues from patient”s own cells, scientists have found that an important cluster of genes is inactivated in induced pluripotent stem cells (iPSCs) that do not have the full development potential of embryonic stem cells.

Generated from adult cells, iPSCs have many characteristics of embryonic stem cells but also have had significant limitations.

“We found that a segment of chromosome 12 containing genes important for fetal development was abnormally shut off in most iPSCs. These findings indicate we need to keep improving the way we produce iPSCs and suggest the need for new reprogramming strategies,” Nature quoted Dr. Konrad Hochedlinger, of the Massachusetts General Hospital Center for Regenerative Medicine (MGH-CRM) and the Harvard Stem Cell Institute (HSCI), who led the study.

Although iPSCs appear quite similar to embryonic stem cells and give rise to many different types of cells, they have important limitations.

Several molecular differences have been observed, particularly in the epigenetic processes that control which genes are expressed, and procedures that are able to generate live animals from the embryonic stem cells of mice are much less successful with iPSCs.

Previous studies have compared iPSCs generated with the help of viruses, which can alter cellular DNA, to embryonic stem cells from unrelated animals.

To reduce the chance that the different sources of the cells were responsible for observed molecular differences, the MGH/HSCI research team prepared two genetically matched cell lines.

After generating mice from embryonic stem cells, they used a technique that does not use viruses to prepare lines of iPSCs from several types of cells taken from those animals.

They then compared the iPSCs with the original, genetically identical embryonic stem cells.

The most stringent assay of cells” developmental potential showed that two tested lines of embryonic stem cells were able to generate live mice as successfully as in previous studies, but no animals could be generated from genetically matched iPSCs.

Closely comparing RNA transcription profiles of several matched cell lines revealed significantly reduced transcription of two genes in the iPSCs.

Both genes are part of a gene cluster on chromosome 12 that normally is maternally imprinted – meaning that only the gene copies inherited from the mother are expressed.

Examination of more than 60 iPSCs lines developed from several types of cells revealed that this gene cluster was silenced in the vast majority of cell lines.

While the gene-silenced iPSCs could generate many types of mouse tissues, their overall developmental potential was limited.

In an assay that produces chimeric animals that incorporate cells from two different stem cells, mice produced from gene-silenced cells had very few tissues that originated from the iPSCs.

However, in a few iPSC lines the gene cluster was normally activated, and in the most rigorous developmental assay, those iPSCs were as successful in producing live animals as embryonic stem cells have been.

According to the authors, this is the first report of animals being produced entirely from adult-derived iPSCs.

The study will appear in the journal Nature. (ANI)

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Gecko-inspired multifocal contact lenses, cameras on the anvil

May 8, 2009 By Leave a Comment

Washington, May 8 (ANI): Scientists are all set to harness the mechanism behind nocturnal geckos’ unique ability to see colours at night, in making multifocal contact lenses and better cameras.

Researchers at Lund University in Sweden have found that the key to the exceptional night vision of the nocturnal helmet gecko is a series of distinct concentric zones of different refractive powers.
The multifocal optical system in geckos is comprised of large cones, which was calculated to be over 350 times more sensitive than human cone vision at the human colour vision threshold.

“We were interested in the geckos because they – and other lizards – differ from most other vertebrates in having only cones in their retina.With the knowledge from the gecko eyes we might be able to develop more effective cameras and maybe even useful multifocal contact lenses,” said project leader Dr. Lina Roth, from the Department of Cell and Organism Biology at the university.

The nocturnal geckos’ multifocal optical system gives them an advantage because light of different ranges of wavelengths can focus simultaneously on the retina.

Another possible advantage of their optical structure is that their eyes allow them to focus on objects at different distances, which makes their multifocal eye to generate a sharp image for at least two different depths.

Roth said that geckos that are active during the day do not possess the distinct concentric zones and are considered monofocal.

The scientists also developed a new method to gather optical data from live animals without any harm to their modifications to the Hartmann-Shack wavefront sensor.

“Studies of animals with relatively large eyes, such as owls and cats, have included surgery and fixation of the head. In this study, we demonstrate that it is possible to obtain high-resolution wavefront measurements of small, unharmed gecko eyes without completely controlling the gaze or the accommodation of the animal eyes,” said the authors.

The study has been published online in the Journal of Vision. (ANI)

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Poorly regulated US wildlife trade threatens public health and ecosystems

May 3, 2009 By Leave a Comment

Washington, May 2 (ANI): In a new report, a team of scientists has determined that the poorly regulated US wildlife trade can lead to devastating effects on ecosystems, native species, food supply chains and human health.

The report has been made by scientists from the Wildlife Trust, Brown University, Pacific Lutheran University, the Centers for Disease Control and Prevention, and the Global Invasive Species Programme.

According to the scientists, the poorly regulated US wildlife trade can lead to devastating effects on ecosystems, native species, food supply chains and human health.

“As our world, in many senses, grows smaller and smaller with the ease of international travel, the network of connections has increased, facilitating the spread of diseases,” said Rita Teutonico, senior advisor for integrative activities in the National Science Foundation’s (NSF) Directorate for Social, Behavioral and Economic Sciences (SBE).

“These scientists report a pattern of trade in wildlife that includes a very large number of animals, coupled with a poor understanding of what species are traded,” said James Collins, NSF Assistant Director for Biological Sciences.

“The findings highlight the need for further research because of the unknown effects these animals and their pathogens can have on native organisms,” he added.

A global trade in wildlife generates hundreds of billions of dollars each year.

The researchers report that during a six-year period from 2000 through 2006, the US imported more than 1.5 billion live animals.

“That’s more than 200 million animals a year – unexpectedly high,” said scientist Peter Daszak, president of the Wildlife Trust, who co-led the research.

The animals collected were from wild populations in more than 190 countries around the world, and were intended for commercial sale in the U.S. – primarily in the pet trade.

“This incredible number of imports is equivalent to every single person in the US owning at least five pets,” said biologist Katherine Smith of Brown University, co-leader of the study.

More than 86 percent of shipments contained animals that were not classified to the level of species, making it impossible to assess the full diversity of animals imported, or calculate the risk of non-native species introductions or disease transmission.

“Shipments are coming in labeled ‘live vertebrate’ or ‘fish’,” said Daszak. “If we don’t know what animals are in there, how do we know which are going to become invasive species or carry diseases that could affect livestock, wildlife – or ourselves?” he added.

“The threat to public health is real, as the majority of emerging diseases come from wildlife,” said Smith. (ANI)

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New fat-fighting pathway could help control liver disease, diabetes

April 2, 2009 By Leave a Comment

London, Apr 2 (ANI): Scientists have discovered a method that can manage the amount of fat that cells store for use as a back-up energy source, and can eventually lead to therapies for liver disease and diabetes.

Researchers at Albert Einstein College of Medicine of Yeshiva University have also found that the process, if disrupted, can enable cellular fat to accumulate, a key factor in age-related metabolic diseases such as obesity and type 2 diabetes.

They reckon that the discovery of this previously unknown fat-fighting pathway may lead to novel drugs for the treatment of metabolic syndrome – characterised by obesity, blood lipid disorders, and insulin resistance – and for a common liver disease known as “fatty liver” or steatohepatitis.

Usually, all cells store lipids, a type of fat, in the form of small droplets that can be broken down for energy when needed.

But in cases of excessive food intake, or in certain diseases like diabetes or obesity, these lipid droplets become so large that they interfere with normal cell function.

“In this study, we found that the amount of fat stored in these intracellular lipid droplets is controlled through autophagy, a process until now thought to help primarily in digesting and recycling damaged cellular structures,” Nature magazine quoted Dr. Mark Czaja, professor of medicine at Einstein, as saying.

Autophagy, also known as the process of “self-eating”, is carried out by lysosomes, which function as the cell’s recycling centre.

The researchers conducted studies of liver cells in culture and in live animals, and discovered a strange lysosomes trait-they continuously remove portions of lipid droplets and process them for energy production.

“When food is scarce, autophagy becomes a main source of energy for the cells and this process of digesting lipid droplets is accelerated. If autophagy slows down, as occurs in aging, the lipid droplets stored in cells keep growing and eventually become so big that they can no longer be degraded,” said a co-uathor of the study.

Such a slowdown in fat control can trigger a vicious cycle in which the enlarging fat droplets impair autophagy, allowing even more fat to accumulate, which could eventually contribute to diseases such as diabetes.

The researchers noted that therapies aimed at helping autophagy operate more efficiently might prevent disease by keeping fat droplets under control. (ANI)

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Nanoparticles created to illuminate tumours for safer drug delivery

February 23, 2009 By Leave a Comment

London, Feb 23 (ANI): Researchers at the University of California, San Diego, have created tiny flakes of silicon that glow brightly and illuminate tumours for a longer time to ensure better drug delivery to cancer patients.

The nano-scale material glows brightly, last long enough to slowly release cancer drugs, and then break down into harmless by-products.

The authors said that it’s the first study to image tumours and organs using biodegradable silicon nano particles in live animals.

“It is the first luminescent nanoparticle that was purposely designed to minimize toxic side effects,” Nature magazine quoted Michael Sailor, a chemistry professor at UCSD who led the study, as saying.

While many nanoparticles tested in research labs are too poisonous for use in humans, “this new design meets a growing need for non-toxic alternatives that have a chance to make it into the clinic to treat human patients,” said Sailor.

While testing the safer nanoparticles in mice, the researchers found that tumours glow for several hours, and then dim as the particles broke down.

Also it was found that levels dropped noticeably in a week and were undetectable after four weeks.

Initially, the particles are thin wafers made porous with an electrical current and then smashed to bits with ultrasound.

With additional treatment, the physical structure of the flakes is altered to make them glow red when illuminated with ultraviolet light.

Luminescent particles can reveal tumours too tiny to detect by other means or allow a surgeon to be sure all of a cancerous growth has been removed.

Also, the researchers claimed that these nanoparticles could help deliver drugs safely. The cancer drug doxorubicin will stick to the pores and slowly escape as the silicon dissolves.

“The goal is to use the nanoparticles to chaperone the drug directly to the tumour, to release it into the tumour rather than other parts of the body,” said Sailor.

Targeted delivery would allow doctors to use smaller doses of the drug. At high doses doxorubicin often has toxic side effects.

The particles, at about 100 nanometers, are bigger than many designed to deliver drugs, and thus they tend to be more effective and safe.

Large particles can hold more of a drug. Yet they self-destruct, and the remnants can be filtered away by the kidneys.

After examining vulnerable organs like liver, spleen and kidney, which help to remove toxins, scientists discovered no lasting changes in mice treated with the new nanoparticles.

The study has been published in Nature Materials. (ANI)

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