Over-expressing a gene that lets brain cells communicate just a fraction of a second longer makes a smarter rat, report researchers from the Medical College of Georgia and East China Normal University.

Dubbed Hobbie-J after a smart rat that stars in a Chinese cartoon book, the transgenic rat was able to remember novel objects, such as a toy she played with, three times longer than the average Long Evans female rat, which is considered the smartest rat strain. Hobbie-J was much better at more complex tasks as well, such as remembering which path she last traveled to find a chocolate treat.

The report comes about a decade after the scientists first reported in the journal Nature that they had developed “Doogie,” a smart mouse that over-expresses the NR2B gene in the hippocampus, a learning and memory center affected in diseases such as Alzheimer’s. Memory improvements they found in the new genetically modified Long Evans rat were very similar to Doogie’s. Subsequent testing has shown that Doogie maintained superior memory as he aged.

“This adds to the notion that NR2B is a universal switch for memory formation,” says Dr. Joe Z. Tsien, co-director of the MCG Brain & Behavior Discovery Institute and co-corresponding author on the paper published Oct. 19 in PLoS One. Dr. Xiaohua Cao at East China Normal University also is a co-corresponding author.

The finding also further validates NR2B as a drug target for improving memory in healthy individuals as well as those struggling with Alzheimer’s or mild dementia, the scientists says.

NR2B is a subunit of NMBA receptors, which are like small pores on brain cells that let in electrically-charged ions that increase the activity and communication of neurons. Dr. Tsien refers to NR2B as the “juvenile” form of the receptor because its levels decline after puberty and the adult counterpart, NR2A, becomes more prevalent.

While the juvenile form keeps communication between brain cells open maybe just a hundred milliseconds longer, that’s enough to significantly enhance learning and memory and why young people tend to do both better, says Dr. Tsien, the Georgia Research Alliance Eminent Scholar in Cognitive and Systems Neurobiology. This trap door configuration that determines not just how much but how fast information flows is unique to NMBA receptors.

Scientists found that Hobbie-J consistently outperformed the normal Long Evans rat even in more complex situations that require association, such as working their way through a water maze after most of the designated directional cues and the landing point were removed. “It’s like taking Michael Jordan and making him a super Michael Jordan,” Deheng Wang, MCG graduate student and the paper’s first author, says of the large black and white rats already recognized for their superior intellect.

But even a super rat has its limits. For example with one test, the rats had to learn to alternate between right and left paths to get a chocolate reward. Both did well when they only had to wait a minute to repeat the task, after three minutes only Hobbie-J could remember and after five minutes, they both forgot. “We can never turn it into a mathematician. They are rats, after all,” Dr. Tsien says, noting that when it comes to truly complex thinking and memory, the size of the brain really does matter.

That’s one of the reasons scientists pursue this type of research: to see if increased production of NR2B in more complex creatures, such as dogs and perhaps eventually humans, gets the same results. He also is beginning studies to explore whether magnesium – a mineral found in nuts, legumes and green vegetables such as spinach – can more naturally replicate the results researchers have obtained through genetic manipulation. Magnesium ion blocks entry to the NMDA receptor so more magnesium forces the brain cell to increase expression levels of the more efficient NR2B to compensate. This is similar to how statin drugs help reduce cholesterol levels in the blood by inhibiting its synthesis in the liver.

Scientists created Hobbie-J and Doogie by making them over-express CaMKII, an abundant protein that works as a promoter and signaling molecule for the NMDA receptor, something that likely could not be replicated in humans. In October 2008, they reported in Neuron that they could also safely and selectively erase old and new memories alike in mice by over-expressing CaMKII while the memory was being recalled

“We want to make sure this is a real phenomenon,” Dr. Tsien says of the apparent connection between higher levels of NR2B and better memory. “You should never assume that discovery you made in a cell line or a mouse can be translated to other species or systems unless you do the experiments.” He adds that the failure of new drugs and other disappointments result from the lack of sufficient scientific evidence.

The transgenic rat has other practical value as well. There is substantial scientific and behavior data already available on rats and because rats are larger, it’s easier to do memory tests and record signals from their brain. For example they are strong enough to press levers to get a food reward and their size and comfort level with water means they won’t just float aimlessly in a water maze as “fluffy” mice tend to do.

A 21-year Michigan State University experiment that distills the essence of evolution in laboratory flasks not only demonstrates natural selection at work, but could lead to biotechnology and medical research advances, researchers said.

E. coli cultures in the laboratory of Michigan State University evolutionary biologist Richard Lenski. (Credit: Greg Kohuth, Michigan State University)

Charles Darwin’s seminal Origin of Species first laid out the case for evolution exactly 150 years ago. Now, MSU professor Richard Lenski and colleagues document the process in their analysis of 40,000 generations of bacteria, published this week in the international science journal Nature.

Lenski, Hannah Professor of Microbial Ecology at MSU, started growing cultures of fast-reproducing, single-celled E. coli bacteria in 1988. If a genetic mutation gives a cell an advantage in competition for food, he reasoned, it should dominate the entire culture. While Darwin’s theory of natural selection is supported by other studies, it has never before been studied for so many cycles and in such detail.

“It’s extra nice now to be able to show precisely how selection has changed the genomes of these bacteria, step by step over tens of thousands of generations,” Lenski said.

Lenski’s team periodically froze bacteria for later study, and technology has since developed to allow complete genetic sequencing. By the 20,000-generation midpoint, researchers discovered 45 mutations among surviving cells. Those mutations, according to Darwin’s theory, should have conferred some advantage, and that’s exactly what the researchers found.

The results “beautifully emphasize the succession of mutational events that allowed these organisms to climb toward higher and higher efficiency in their environment,” noted Dominique Schneider, a molecular geneticist at the Université Joseph Fourier in Grenoble, France.

Lenski’s long-running experiment itself is uniquely suited to answer some critical questions — such as whether rates of change in a bacteria’s genome move in tandem with its fitness to survive.

“The coupling between genomic and adaptive evolution is complex and can be counterintuitive,” Lenski concluded. “The genome was evolving along at a surprisingly constant rate, even as the adaptation of the bacteria slowed down a lot. But then suddenly the mutation rate jumped way up, and a new dynamic relationship was established.”

A mutation involved in DNA metabolism arose around generation 26,000, causing the mutation rate everywhere else in the genome to increase dramatically. The number of mutations jumped to 653 by generation 40,000, but researchers surmise that most of the late-evolving mutations were not helpful to the bacteria.

Gene mutations involved in human DNA replication are involved in some cancers. Many of the patterns observed in the experiment also occur in certain microbial infections, “and cancer progression is a fundamentally similar evolutionary process,” observed collaborator Jeffrey Barrick. “So what we learn here can help us better understand the course of these diseases.”

Barrick, a postdoctoral researcher in MSU’s Department of Microbiology and Molecular Genetics, developed computational tools to discover and validate often complex mutations. “We know an astounding amount about the details of evolution in these little Erlenmeyer flasks,” he said.

The Nature paper involved collaboration with scientists from South Korea as well as France and MSU. The research, said genomics team leader Jihyun Kim of the Korea Research Institute of Bioscience and Biotechnology, “is not only useful in understanding the tempo and mode of evolution, but can serve as a nice framework for practical applications in biotechnology, such as improving the performance or productivity of an industrial strain.”

Thousands of generations later, the MSU experiment continues to evolve. “Like a lot of science, our study answers some questions but raises many others,” Lenski said.

The research has been supported by the National Science Foundation and the Defense Advanced Research Projects Agency.

]*?)href\s*=\s*['"](.*?)['"]([^>]*)>(.*?) Ending uga_filter:

A 21-year Michigan State University experiment that distills the essence of evolution in laboratory flasks not only demonstrates natural selection at work, but could lead to biotechnology and medical research advances, researchers said.

E. coli cultures in the laboratory of Michigan State University evolutionary biologist Richard Lenski. (Credit: Greg Kohuth, Michigan State University)

Charles Darwin’s seminal Origin of Species first laid out the case for evolution exactly 150 years ago. Now, MSU professor Richard Lenski and colleagues document the process in their analysis of 40,000 generations of bacteria, published this week in the international science journal Nature.

Lenski, Hannah Professor of Microbial Ecology at MSU, started growing cultures of fast-reproducing, single-celled E. coli bacteria in 1988. If a genetic mutation gives a cell an advantage in competition for food, he reasoned, it should dominate the entire culture. While Darwin’s theory of natural selection is supported by other studies, it has never before been studied for so many cycles and in such detail.

“It’s extra nice now to be able to show precisely how selection has changed the genomes of these bacteria, step by step over tens of thousands of generations,” Lenski said.

Lenski’s team periodically froze bacteria for later study, and technology has since developed to allow complete genetic sequencing. By the 20,000-generation midpoint, researchers discovered 45 mutations among surviving cells. Those mutations, according to Darwin’s theory, should have conferred some advantage, and that’s exactly what the researchers found.

The results “beautifully emphasize the succession of mutational events that allowed these organisms to climb toward higher and higher efficiency in their environment,” noted Dominique Schneider, a molecular geneticist at the Université Joseph Fourier in Grenoble, France.

Lenski’s long-running experiment itself is uniquely suited to answer some critical questions — such as whether rates of change in a bacteria’s genome move in tandem with its fitness to survive.

“The coupling between genomic and adaptive evolution is complex and can be counterintuitive,” Lenski concluded. “The genome was evolving along at a surprisingly constant rate, even as the adaptation of the bacteria slowed down a lot. But then suddenly the mutation rate jumped way up, and a new dynamic relationship was established.”

A mutation involved in DNA metabolism arose around generation 26,000, causing the mutation rate everywhere else in the genome to increase dramatically. The number of mutations jumped to 653 by generation 40,000, but researchers surmise that most of the late-evolving mutations were not helpful to the bacteria.

Gene mutations involved in human DNA replication are involved in some cancers. Many of the patterns observed in the experiment also occur in certain microbial infections, “and cancer progression is a fundamentally similar evolutionary process,” observed collaborator Jeffrey Barrick. “So what we learn here can help us better understand the course of these diseases.”

Barrick, a postdoctoral researcher in MSU’s Department of Microbiology and Molecular Genetics, developed computational tools to discover and validate often complex mutations. “We know an astounding amount about the details of evolution in these little Erlenmeyer flasks,” he said.

The Nature paper involved collaboration with scientists from South Korea as well as France and MSU. The research, said genomics team leader Jihyun Kim of the Korea Research Institute of Bioscience and Biotechnology, “is not only useful in understanding the tempo and mode of evolution, but can serve as a nice framework for practical applications in biotechnology, such as improving the performance or productivity of an industrial strain.”

Thousands of generations later, the MSU experiment continues to evolve. “Like a lot of science, our study answers some questions but raises many others,” Lenski said.

The research has been supported by the National Science Foundation and the Defense Advanced Research Projects Agency.

Start uga_filter:

A magnetic charge can behave and interact just like an electric charge in some materials, according to new research led by the London Centre for Nanotechnology (LCN).

The magnetic equivalent of electricity in a 'spin ice' material: atom sized north and south poles in spin ice drift in opposite directions when a magnetic field is applied.

The findings could lead to a reassessment of current magnetism theories, as well as significant technological advances.

The research, published in Nature, proves the existence of atom-sized ‘magnetic charges’ that behave and interact just like more familiar electric charges. It also demonstrates a perfect symmetry between electricity and magnetism – a phenomenon dubbed ‘magnetricity’ by the authors from the LCN and the Science and Technology Facility Council’s ISIS Neutron and Muon Source.

In order to prove experimentally the existence of magnetic current for the first time, the team mapped Onsager’s 1934 theory of the movement of ions in water onto magnetic currents in a material called spin ice. They then tested the theory by applying a magnetic field to a spin ice sample at a very low temperature and observing the process using muons at ISIS.

The experiment allowed the team to detect magnetic charges in the spin ice (Dy₂Ti₂O₇), to measure their currents, and to determine the elementary unit of the magnetic charge in the material. The monopoles they observed arise as disturbances of the magnetic state of the spin ice, and can exist only inside the material.

Professor Steve Bramwell, LCN co-author of the paper, said: “Magnetic monopoles were first predicted to exist in 1931, but despite many searches, they have never yet been observed as freely roaming elementary particles. These monopoles do at least exist within the spin ice sample, but not outside.

“It is not often in the field of physics you get the chance to ask ‘How do you measure something?’ and then go on to prove a theory unequivocally. This is a very important step to establish that magnetic charge can flow like electric charge. It is in the early stages, but who knows what the applications of magnetricity could be in 100 years time.”

Professor Keith Mason, Chief Executive of STFC said: “The unequivocal proof that magnetic charge is conducted in spin ice adds significantly to our understanding of electromagnetism. Whilst we will have to wait to see what applications magnetricity will find in technology, this research shows that curiosity driven research will always have the potential to make an impact on the way we live and work. Advanced materials research depends greatly on having access to central research labs like ISIS allowing the UK science community to flourish and make exciting discoveries like this.”

Dr Sean Giblin, instrument scientist at ISIS and co-author of the paper, added: “The results were astounding, using muons at ISIS we are finally able to confirm that magnetic charge really is conducted through certain materials at certain temperatures – just like the way ions conduct electricity in water.”

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A magnetic charge can behave and interact just like an electric charge in some materials, according to new research led by the London Centre for Nanotechnology (LCN).

The magnetic equivalent of electricity in a 'spin ice' material: atom sized north and south poles in spin ice drift in opposite directions when a magnetic field is applied.

The findings could lead to a reassessment of current magnetism theories, as well as significant technological advances.

The research, published in Nature, proves the existence of atom-sized ‘magnetic charges’ that behave and interact just like more familiar electric charges. It also demonstrates a perfect symmetry between electricity and magnetism – a phenomenon dubbed ‘magnetricity’ by the authors from the LCN and the Science and Technology Facility Council’s ISIS Neutron and Muon Source.

In order to prove experimentally the existence of magnetic current for the first time, the team mapped Onsager’s 1934 theory of the movement of ions in water onto magnetic currents in a material called spin ice. They then tested the theory by applying a magnetic field to a spin ice sample at a very low temperature and observing the process using muons at ISIS.

The experiment allowed the team to detect magnetic charges in the spin ice (Dy₂Ti₂O₇), to measure their currents, and to determine the elementary unit of the magnetic charge in the material. The monopoles they observed arise as disturbances of the magnetic state of the spin ice, and can exist only inside the material.

Professor Steve Bramwell, LCN co-author of the paper, said: “Magnetic monopoles were first predicted to exist in 1931, but despite many searches, they have never yet been observed as freely roaming elementary particles. These monopoles do at least exist within the spin ice sample, but not outside.

“It is not often in the field of physics you get the chance to ask ‘How do you measure something?’ and then go on to prove a theory unequivocally. This is a very important step to establish that magnetic charge can flow like electric charge. It is in the early stages, but who knows what the applications of magnetricity could be in 100 years time.”

Professor Keith Mason, Chief Executive of STFC said: “The unequivocal proof that magnetic charge is conducted in spin ice adds significantly to our understanding of electromagnetism. Whilst we will have to wait to see what applications magnetricity will find in technology, this research shows that curiosity driven research will always have the potential to make an impact on the way we live and work. Advanced materials research depends greatly on having access to central research labs like ISIS allowing the UK science community to flourish and make exciting discoveries like this.”

Dr Sean Giblin, instrument scientist at ISIS and co-author of the paper, added: “The results were astounding, using muons at ISIS we are finally able to confirm that magnetic charge really is conducted through certain materials at certain temperatures – just like the way ions conduct electricity in water.”

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