Stress-related Disorders Affect Brain’s Processing Of Memory

ScienceDaily (Dec. 18, 2008) — Researchers using functional MRI (fMRI) have determined that the circuitry in the area of the brain responsible for suppressing memory is dysfunctional in patients suffering from stress-related psychiatric disorders. Results of the study will be presented December 3 at the annual meeting of the Radiological Society of North America (RSNA).
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"For patients with major depression and other stress-related disorders, traumatic memories are a source of anxiety," said Nivedita Agarwal, M.D., radiology resident at the University of Udine in Italy, where the study is being conducted, and research fellow at the Brain Imaging Center of McLean Hospital, Department of Psychiatry at Harvard Medical School in Boston. "Because traumatic memories are not adequately suppressed by the brain, they continue to interfere with the patient's life."
Dr. Agarwal and colleagues used brain fMRI to explore alterations in the neural circuitry that links the prefrontal cortex to the hippocampus, while study participants performed a memory task. Participants included 11 patients with major depression, 13 with generalized anxiety disorder, nine with panic attack disorders, five with borderline personality disorder and 21 healthy individuals. All patients reported suffering varying degrees of stressful traumatic events, such as sexual or physical abuse, difficult relationships or "mobbing" – a type of bullying or harassment – at some point in their lives.
After reviewing a list of neutral word pairs, each participant underwent fMRI. During imaging, they were presented with one of the words and asked to either recall or to suppress the memory of its associated word.
The fMRI images revealed that the prefrontal cortex, which controls the suppression and retrieval of memories processed by the hippocampus, showed abnormal activation in the patients with stress-related disorders compared to the healthy controls. During the memory suppression phase of the test, patients with stress-related disorders showed greater activation in the hippocampus, suggesting that insufficient activation of the prefrontal cortex could be the basis for inadequate suppression of unwanted traumatic memories stored in the hippocampus.
"These data suggest that the mechanism for memory suppression is dysfunctional in patients with stress-related disorders primarily because of an alteration of the prefrontal cortex," Dr. Agarwal said. "These patients often complain of poor memory, which might in part be attributed to this altered circuitry," she added.
According to Dr. Agarwal, fMRI is an important tool in understanding the neurobiological basis of psychiatric disorders and in identifying imaging markers to psychiatric disease, helping clinicians target specific parts of the brain for treatment.
The study's principal investigator is Paolo Brambilla, M.D., Ph.D. Co-authors are Monica Baiano, M.D., Ph.D., Massimo Bazzocchi, M.D., Giuseppe Como, M.D., and Marta Maieron, Ph.D.

Gene That Controls Fruit Shape

ScienceDaily (Mar. 17, 2008) — Crop scientists have cloned a gene that controls the shape of tomatoes, a discovery that could help unravel the mystery behind the huge morphological differences among edible fruits and vegetables, as well as provide new insight into mechanisms of plant development.
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The gene, dubbed SUN, is only the second ever found to play a significant role in the elongated shape of various tomato varieties, said Esther van der Knaap, lead researcher in the study and assistant professor of horticulture and crop science at Ohio State University's Ohio Agricultural Research and Development Center (OARDC) in Wooster.
One of the most diverse vegetable crops in terms of shape and size variations, tomatoes have evolved from a very small, round wild ancestor into the wide array of cultivated varieties -- some large and segmented, some pear-shaped, some oval, some resembling chili peppers -- available through most seed catalogs and for sale in supermarkets. However, very little is known about the genetic basis for such transformations in tomatoes, and virtually nothing has been discerned about morphological changes in other fruits and vegetables.
"Tomatoes are the model in this emerging field of fruit morphology studies," van der Knaap pointed out. "We are trying to understand what kind of genes caused the enormous increase in fruit size and variation in fruit shape as tomatoes were domesticated. Once we know all the genes that were selected during that process, we will be able to piece together how domestication shaped the tomato fruit -- and gain a better understanding of what controls the shape of other very diverse crops, such as peppers, cucumbers and gourds."
One of the first pieces in van der Knaap's fruit-development puzzle is SUN, which takes its name from the "Sun 1642" cultivated variety where it was found -- an oval-shaped, roma-type tomato with a pointy end. The gene also turned out to be very common in elongated heirloom varieties, such as the Poblano pepper-like "Howard German" tomato.
"After looking at the entire collection of tomato germplasm we could find, we noticed that there were some varieties that had very elongated fruit shape," van der Knaap explained. "By genetic analysis, we narrowed down the region of the genome that controls this very elongated fruit shape, and eventually narrowed down that region to a smaller section that we could sequence to find what kind of genes were present at that location.
"In doing that," van der Knaap continued, "we identified one key candidate gene that was turned on at high levels in the tomato varieties carrying the elongated fruit type, while the gene was turned off in round fruit. And after we confirmed that observation in several other varieties, we found that this gene was always very highly expressed in varieties that carry very elongated fruit."
Once SUN was identified, the next step involved proving whether this gene was actually responsible for causing changes in fruit shape. To do so, van der Knaap and her team conducted several plant-transformation experiments. When the SUN gene was introduced into wild, round fruit-bearing tomato plants, they ended up producing extremely elongated fruit. And when the gene was "knocked out" of elongated fruit-bearing plants, they produced round fruit similar to the wild tomatoes.
"SUN doesn't tell us exactly how the fruit-shape phenotype is altered, but what we do know is that turning the gene on is very critical to result in elongated fruit," van der Knaap said. "We can now move forward and ask the question: Does this same gene, or a gene that is closely related in sequence, control fruit morphology in other vegetables and fruit crops?"
Something else van der Knaap and her team found out is that SUN encodes a member of the IQ67 domain of plant proteins, called IQD12, which they determined to be sufficient -- on its own -- to make tomatoes elongated instead of round during the plant transformation experiments.
IQD12 belongs to a family of proteins whose discovery is relatively new in the world of biology. So new that IQD12 is only the second IQ67 protein-containing domain whose function in plants has been identified. The other one is AtIQD1, discovered in the plant model Arabidopsis thaliana, which belongs to the same family as broccoli and cabbage. In Arabidopsis, AtIQD1 increases levels of glucosinolate, a metabolite that Ohio State researchers are studying in broccoli for its possible role in inhibiting cancer
"Unlike AtIQD1, SUN doesn't seem to be affecting glucosinolate levels in tomato, since these metabolites are not produced in plants of the Solanaceous family (which includes tomato, peppers, eggplant and other popular crops)," van der Knaap explained. "But there appears to be a common link between the two genes, which is that they may be regulating tryptophan levels in the plant. Thus, SUN may be telling us more about the whole process of diversification in fruits and across plant species, perhaps through its impact on plant hormones and/or secondary metabolites levels."
In the process of identifying and cloning SUN, van der Knaap's team was also able to trace the origin of this gene and the process by which it came to reside in the tomato genome.
Another unique characteristic of the SUN gene is that it affects fruit shape after pollination and fertilization, with the most significant morphological differences found in developing fruit five days after plant flowering. The only other fruit-shape gene previously identified -- OVATE, a discovery by Cornell University plant breeder Steven Tanksley, van der Knaap's advisor while she was a post-doctoral associate there -- influences the future look of a fruit before flowering, early in the ovary development.
The discovery was reported, as the cover article, in the March 14 issue of the journal Science.
Co-authors in the Science paper include Eric Stockinger, associate professor of horticulture and crop science at OARDC; Han Xiao, a postdoctoral researcher in horticulture and crop science at Ohio State; Ning Jiang, assistant professor of horticulture at Michigan State University; and Erin Schaffner, a former undergraduate student from the College of Wooster who conducted her independent study in van der Knaap's lab.
Funding for this research came from the National Science Foundation (NSF).

Dolly the Sheep is dead

Dolly the Sheep is dead - possibly the world's most famous animal was put to sleep on 14th February 2003 after developing progressive lung disease. Dolly was cloned from a dead adult sheep using frozen cells and born on 5th July 1996. There have been many reports that Dolly may have been getting old before her time, developing arthritis and possibly other problems. Scientists are waiting for the results of a post mortem to try to understand whether Dolly's latest problems were linked to the cloning technique, which commonly causes severe abnormalities. The big worry is whether teams trying to clone human babies will accidentally create very sick children.Clonaid claims birth of first human clone (Eve) by caesarian section on 26th December 2002 and a second child in Europe (Netherlands) to a lesbian couple in early January, a third in late January to a Japanese couple who cloned their dead son, plus another to a couple from Saudi Arabia and a further child - country of origin not declared. But no evidence of any kind had been offered by mid February to substantiate their claims.Born outside the US to an American woman, Eve was apparently created using Dolly technology - a skin cell and a human egg from the "mother" who is infertile. Clonaid claims 3 other "mothers" will give birth soon, one of which is carrying a twin of a dead child.While many experts expressed doubts about the claims, Clonaid said that independent gene testing would prove the claim about Eve in less than a week. This promise was withdrawn after a lawsuit was begun in the US to make Eve a ward of court, on the basis that the "mother" was the baby girl's twin sister and the "mother" had no legal parental rights even though she had just given birth to her own twin. A similar court case was launched in the Netherlands after reports that the second birth was to a Dutch lesbian. Clonaid say that the "parents" are afraid their cloned babies will be seized and taken away from them permanently. In early February Clonaid said that testing of the Japanese baby boy was under way.

General Information

General Information
Cloning - A collection of resources from MEDLINEplus, a service of the U.S. National Library of Medicine and the National Institutes of Health.
Cloning In Focus - An excellent introduction to cloning from the Genetic Science Learning Center. Teacher resources covering cloning and other genetics topics also are available. http://www.bbc.co.uk/science/genes/gene_safari/clone_zone/intro.shtml The
Clone Zone - An introduction to cloning provided by the British
Broadcasting Corporation (BBC). -->
Cloning: How It Works - An interactive guide to cloning with graphics and animations provided by Guardian Unlimited.
Creating a Cloned Sheep Named Dolly - General information on cloning from the National Institutes of Health Office of Science Education. For grades 9-12.
How Cloning Works - from the How Stuff Works Web site.
How Human Cloning Will Work - from the How Stuff Works Web site
Weblog Special: Human Cloning
Cloning - Introduction to cloning and stem cells. An issue brief from the Genetics & Public Policy Center.
Cloning in the News
The Real Face of Cloning - From USA Today (January 17, 2003)
The History of Cloning - From MSNBC News. A timeline outlining a brief history of cloning.
Cloning Ethics
The Politics of Human Biotechnology: Overview - Center for Genetics and Society.
Primer on Ethics and Human Cloning - A 2001 actionbioscience.org original article by Glenn McGee, Ph.D.
Beyond Dolly the Human Cloning Dilemma - From MSNBC.
Human Cloning and Human Dignity: An Ethical Inquiry - 2002 human cloning report published by The President's Council on Bioethics. Includes ethical discussions and policy recommendations.
Sex and Cloning - From NewScientist.com (requires subscription).
National Information Resource on Ethics & Human Genetics - Includes GenETHX, the genetics and ethics database.
Cat Cloning is Wrong-Headed States The Humane Society of the United States - Press release (2002) from the Humane Society of the United States advising against the cloning of cats and other pets.
Policy and Legislation (focus on U.S. policy)
Federal Policies on Cloning - A summary of U.S. efforts (1991 to 2003) to pass cloning legislation from the Center for Genetics and Society.
State Human Cloning Laws - An overview from the National Conference of State Legislatures.
Hot Topic: Cloning - A collection of legislative and other cloning resources. Provided by the National Conference of State Legislatures.
Database of Global Policies on Human Cloning and Germ-line Engineering - A database of cloning legislation from around the world. Provided by the Global Lawyers and Physicians, a non-profit organization working on health and human rights issues.
Policy Brief: Human Cloning - From the American Association for the Advancement of Science
Why We Should Not Clone Humans - From the American Medical Association.
Bills Introduced to Congress
H.R.2560 - Human Cloning Prohibition Act of 2007
H.R.2564 - Human Cloning Prohibition Act of 2007
S. 812 - Human Cloning Ban and Stem Cell Research Protection Act of 2007 S.303.IS
(PDF) - Human Cloning Ban and Stem Cell Research Protection Act of 2003.
Introduced in Senate February 5, 2003.
S.245.IS
(PDF) - Human Cloning Prohibition Act of 2003. Introduced in Senate January
29, 2003. -->
Cloning Problems
TIME Collection: Cloning - Archive of articles from Time Magazine
Cloned Mice Have Genomic Flaws - Article from the Genome News Network (September 2002).
Tears of a Clone - Article from The Guardian (April 19, 2002).
Cloned Monkey Embryos Are a "Gallery of Horrors" - Article from NewScientist.com (December 12, 2001).
Imprinting Marks Clones for Death: Unstable Genes Make Normal Clones Unlikely - Article from Nature News Service (July 6, 2001).
Clones Contain Hidden DNA Damage - Article from NewScientist.com (July 6, 2001).
Cloned Animals
TIME Collection: Cloning - Archive of articles from Time Magazine
Cloned Rabbits Produced by Nuclear Transfer from Adult Somatic Cells - Article from the April 2002 issue of Nature Biotechnology.
Endangered wild sheep clone reported to be healthy - Article from the Genome News Network (October 12, 2001).
First Cloned Mouse Dies Of Old Age - Report from CBSNEWS.com (May 10, 2000).
Pigs Cloned for First Time - Article from the April 2000 issue of Nature Biotechnology.
Cloning Noah's Ark - Article on cloning endangered species from the November 2000 issue of Scientific American (requires subscription).
First Male Clone - Article from Nature News Service about the first successfully cloned male animal, a mouse (1999).
A Clone in Sheep's Clothing - Article in Scientific American reporting the cloning of Dolly (March 3, 1997).
Cloning for Organs
Cloned Pigs Raise Transplant Hopes - Article from the August 22, 2002, issue of BBC News.
Building Brand New Kidneys - Article from the February 13, 2002, issue of The Scientist (requires subscription).
Scientists Produce Five Pig Clones - Article from the March 14, 2000, issue of BBC News.
More Information
Roslin Institute - Learn more about Dolly's home.
Hello Dolly: A WebQuest -Web-based curriculium for teaching cloning.
Cloning: From DNA Molecules to Dolly - Human Genome News article (January 1998).
Genome Audio Files - Page down for several real audio interviews on cloning.

Advanced Cell Technology

Advanced Cell Technology (ACT), a biotechnology company formed in 1994, is involved with therapeutic cloning and the cloning of animals. Among the animals it has cloned are transgenic cows. [1]
ACT's Chief Scientific Officer is Robert Lanza, who also is also Adjunct Professor at Wake Forest University School of Medicine.
At 7:30 PM on Monday, 8 January 2001, with the birth of a gaur named Noah at Trans Ova Genetics, in Sioux Center Iowa, ACT became the first biotechnology company to succeed at cloning an animal from an endangered species. Noah was carried and brought successfully by a surrogate mother from another, more common, species, in this case a domestic cow named Bessie. While healthy at birth, Noah died within 48 hours of a common dysentery, likely unrelated to cloning. [2]
In 2001, scientists at ACT cloned the first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.[3]
ACT received the 2004 Corporate World Technology Award for biotechnology.[citation needed]
On August 23, 2006, the online edition of Nature scientific journal published a paper by Dr. Lanza stating that his team had found a way to extract embryonic stem cells without destroying the actual embryo, deriving a stem cell line using a process similar to preimplantation genetic diagnosis, in which a single blastomere is extracted from a blastocyst.[4] This technical achievement would potentially enable scientists to work with new lines of embryonic stem cells derived using public funding. Federal funding is currently limited to research using embryonic stem cell lines derived prior to August 2001.
The company currently trades under the symbol of "ACTC".

History of Cloning

It seems that every week, newspapers report on new advances in the science of cloning. Everybody knows about Dolly the cloned sheep, but few people know all the details about cloning, including the fact that scientists have been working on it for over 100 years.
Cloning in Nature Cloning has been going on in the natural world for thousands of years. A clone is simply one living thing made from another, leading to two organisms with the same set of genes. In that sense, identical twins are clones, because they have identical DNA. Sometimes, plants are self-pollinated, producing seeds and eventually more plants with the same genetic code. Some forests are made entirely of trees originating from one single plant; the original tree spread its roots, which later sprouted new trees. When earthworms are cut in half, they regenerate the missing parts of their bodies, leading to two worms with the same set of genes. However, the ability to intentionally create a clone in the animal kingdom by working on the cellular level is a very recent development.
Early Progress The first cloned animals were created by Hans Dreisch in the late 1800's. Dreich's original goal was not to create identical animals, but to prove that genetic material is not lost during cell division. Dreich's experiments involved sea urchins, which he picked because they have large embryo cells, and grow independently of their mothers. Dreich took a 2 celled embryo of a sea urchin and shook it in a beaker full of sea water until the two cells separated. Each grew independently, and formed a separate, whole sea urchin. In 1902, another scientist, embryologist Hans Spemman, used a hair from his infant son as a knife to separate a 2-celled embryo of a salamander, which also grow externally. He later separated a single cell from a 16-celled embryo. In these experiments, both the large and the small embryos developed into identical adult salamanders. Spemman went on to propose what he called a "fantastical experiment" -- to remove the genetic material from an adult cell, and use it to grow another adult. In this way, he theorized, he would be able to prove that no genetic material was lost as cells grew and divided.
New Advances There were no major advances in cloning until November of 1951, when a team of scientists in Philadelphia working at the lab of Robert Briggs cloned a frog embryo. This team did not simply break off a cell from an embryo, however. They took the nucleus out of a frog embryo cell and used it to replace the nucleus of an unfertilized frog egg cell, completing the "fantastical experiment" of nearly 50 years before. Once the egg cell detected that it had a full set of chromosomes, it began to divide and grow. This was the first time that this process, called nuclear transplant, was ever used, and it continues to be used today, although the method has changed slightly.
False Hopes In 1977, a German scientist shocked the world, claiming to have cloned three mice from embryos. Although embryos had been cloned before, no one had been able to do the experiment with mice because the cells were so small and the tools so large that the cells were traumatized and would eventually die after a few divisions. He instantly became famous, telling the world how he cloned his mice. However, he refused to actually demonstrate any of his techniques, and when other scientists couldn't replicate his work, he came under suspicion. He was challenged -- repeat his work or be discredited. He accepted. He claimed to work nights and mornings when no one was around, but the equipment was never disturbed. He showed off his mouse embryos' growth daily, even though a malfunction in the water purification system left other scientists at his lab unable to grow other embryos. Later, in his cabinet, test tubes were found with mouse embryos in them, each at a different stage of development. Most scientists do not believe that this scientist was ever able to clone adult mice. In 1978, a science fiction writer published a book claiming that a millionaire (known to the readers only as Max) had come to him because of his connections as a writer, and asked the him to arrange for Max to be cloned. The author eventually agreed, as the story goes, and Max was cloned. The book was ranked in the Top 10 list of popular books. Scientists who read his book, however, noticed discrepancies between the book and scientific data. One man who was quoted in the book was angry enough to sue. The publisher admitted that the book was a hoax, but the author maintains his claim to this day. Within these two years, two front-page advances in cloning were discovered to be, most likely, frauds. As a direct result, many scientists began to claim that cloning of mammals was impossible. Funding and interest dropped, and cloning returned to the realm of science fiction for several years.
First Cloned Mammals A breakthrough came in 1986. Two teams, working independently but using nearly the same method, each on opposites side of the Atlantic, announced that they had cloned a mammal. One team was led by Steen Willadsen in England, which cloned a sheep's embryo. The other team was led by Neal First in America, which cloned a cow's embryo. Many advances were made during the course of these experiments, including progress in keeping tissue alive in lab conditions. However, neither team believed that it was possible to clone from an adult's cells. With no progress in sight, the prospect of cloning fell by the wayside, and little research was done on the matter.
Dolly Ian Wilmut at the Roslin Institute in Scotland was assigned to a project in 1986. His goal was to create a sheep that produced a certain chemical in its milk. He chose to alter adult cells, which held up well in laboratory conditions, and then clone them, producing animals with the altered gene all throughout their bodies. He began the paperwork in 1987, and began research in 1990. One of Wilmut's colleagues, who had experience with cloning from early embryo cells, suggested that the reason so many cloning attempts failed was that the cells were in incompatible stages of life. In one stage, the cells are adding to the DNA, in another, they are proofreading it, and in another, splitting it. The cells, he theorized, could not always start over. Wilmut's team learned that by starving the cells, they could be forced into what is called the G0 phase, similar to cellular hibernation. This advance increased the survival rate of the cloned cells; Megan and Morag, two lambs, were cloned from sheep embryos. Wilmut's team now realized that differentiation did not matter in cloning. More work was done, and on July 5, 1996, a lamb was born, cloned from a frozen mammary cell from another adult sheep. Wilmut, who names his animals very creatively, named her Dolly after Dolly Parton. Although Dolly was just a step in a long experiment, the press descended upon the first animal cloned from an adult. The Roslin Institute was overrun with journalists and reporters. However, other scientists were critical -- Dolly took 277 tries to create, and other labs were unable to reproduce the results. In addition, it took over a year for the institute to test Dolly's DNA to make sure that it was indeed the same as that of the frozen mammary cells. Science, although temporarily impressed, demanded a better way.
Herd of Mice Oct 3, 1997, the Honolulu Technique created Cumulina the cloned mouse. She was cloned from cumulus cells (cells which surround developing egg cells) using traditional nuclear transfer. The nucleus was taken from the cumulus cell and implanted in an egg cell from another mouse. The new cell was then treated with a chemical to make it grow and divide. The scientists repeated the process for three generations, yielding over fifty mice that are virtually identical by the end of July, 1998. The Honolulu Technique's success rate of 50:1 is almost six times better than that of the Roslin Institute's success rate, 277:1. As cloning technology improves, more and more applications will be seen in everyday life.
Mainstream Cloning How much do you love your dog? Is your dog so perfect that you would pay over $2.3 million dollars to have another just like it? One couple thinks their 11-year-old dog is just such an animal. Wishing to remain anonymous to avoid run-ins with the press, this couple has contracted Texas A&M University to clone their dog, Missy. Scientists are hailing this for its scientific achievement; no dogs have been cloned before because their reproductive system is rather complicated. If the cloning of dogs can be achieved, perhaps exceptional animals like rescue animals can be reproduced. In addition to the pure scientific appeal of cloning a dog, the attempt to clone Missy has another interesting addition to make to the history of cloning. A private couple wants their dog cloned. They are, of course, spending millions to have her cloned, but consider the possibilities. Could cloning the family pet one day become a normal alternative to buying a new one?
Applications Reliable cloning can be used to make farming more productive by replicating the best animals. It can make medical testing more accurate by providing test subjects that all react the same way to the same drug. It can allow mass production of genetically altered animals, plants, and bacteria. It may settle once and for all what part of personality is dependent on genetics and what part on environment. In short, it can be beneficial to almost every area of biological science.